Contents

Contributors Vl

Preface V ll

Acknowledgements Vlll

1. Ocular Examination David Spalton • Graham Holder • Susana Morley 1

2. The Eyelids Eric Barnes • Richard Collin 35
3. The Conjunctiva: Diseases and Tumours Frank Larkin ~ Paul Hunter 61
4. Infections of the Outer Eye Frank Larkin • Paul Hunter 87
5. Allergic Eye Diseases, Episcleritis and Scleritis Frank Larkin • Paul Hunter 117
6. The Cornea Stephen Tuft 147
7. Primary Glaucoma David Garway-Heath • Paul Foster • Roger Hitchings 187
8. Secondary Glaucoma Keith Barton 221
9. The Uveal Tract Berti! Damato • David Spalton 257
10. Intraocular Inflammation Miles Stanford • David Spalton 289
11. The Lens David Spalton 333
12. Vitreous and Vitreoretinal Disorders Thomas Williamson 363
13. The Norma.l Retina, Retinal Imaging and the Interpretation of Pathological Changes
David Spalton • John Marshall • Victor Chong 397
14. The Retina: Vascular Diseases I David Spalton • Jaheed Khan • John Shilling • Victor Chong 437
15. The Retina: Vascular Diseases II Jaheed Khan • Victor Chong • David Spalton 471
16. Retinal Degenerations Jaheed Khan • Victor Chong
Retinal Dystrophies Michel Michaelides • Anthony Moore 511
17. The Optic Disc Gordon Plant • David Spalton 561
18. Strabismus Christopher Hammond • Elizabeth Tomlin 603
19. Neuro-Ophthalmology GordonPlant • David Spalton 635
20. The Orbit and Lacrimal System James Uddin • Geoffrey Rose 671

Further Reading 707

Index 709

\
Ocular Examination
David Spalton, Graham Holder, Susana Morley

Psychophysical Tests of Visual Function

Visual Acuity
Contrast Sensitivity
Colour Vision
Visual Field Tests
Ocular Examination
Imaging the Globe and Orbit
Electrical Tests of Retinal Function
 PSYCHOPHYSICAL TESTS OF VISUAL FUNCTION
Vision arises from the detection and subsequent processing of
light stimuli from the external environment and the integration
of several different sets of information. Visual acuity, colour
vision and visual fields are routinely assessed in clinical practice.
The visual system also detects other modalities such as
VISUAL ACUITY
The measurement of visual acuity is the first essential part of any
ocular examination and, although the examination technique is
simple, the process being assessed is complex and requires the
interaction of many factors, both physiological and
psychological. Assessment of visual acuity requires the eye to
detect the object and resolve it into its component parts. This
information is then transmitted to the cerebral cortex where it is
matched against existing memory shapes. The patient must then
be able to communicate recognition of the object to the
examiner. Physiologically, visual acuity measures the capability of
the visual system to resolve a target; this is dependent on three
main factors : the background illumination, the contrast of the
target to the background and the angle that the target subtends
at the nodal point of the eye.
In theory the eye has a maximal resolution of 1 minute of arc
at the nodal point. In practice, young people normally have a
better acuity than this at 20/ 15 (6/5) which corresponds to the
spacing of individual cones in the foveola. Although visual acuity
is primarily a function of cones the degree of visual processing in
the retina must be considered and, in particular, the receptive
fields of the retinal ganglion cells. In the foveola there is a 1 : 1
relationship of cones to ganglion cells but this increases rapidly
more peripherally. There is an increasing loss of visual acuity with
age so that in old age 20/30 (6/9) or even 20/40 (6/ 12) may be
considered normal.
Although distance acuity is normally measured clinically near
vision is in some ways more important in the daily life of the patient.
Table 1.1 Factors that limit visual acuity
Steps in visual perception Physiological factors
Image formation on the retina Refractive error
Image detecti on by Cone receptor function (retinal
photoreceptors adaptation)
Init ia l data processing and Optic nerve axonal content
transmission
Higher visual processi ng
luminance or motion but these are not normally investigated in
routine clinical examination. Clinicians need to understand
exactly what such tests measure, how they should be used and
their limitations.
Near vision is tested by reading test print of standardized sizes with
the appropriate spectacle correction and good illumination.
Factors of accommodation and magnification are important in the
assessment of near vision and the correlation between distance
acuity and near acuity is not always good. Patients with 20/60
(6/ 18) distance vision can often manage to read print of}3 (N5)
size, provided their macular function is normal. There appears to be
a large redundancy of nerve fibres in the visual pathways: probably
only approximately 15 per cent of the optic nerve fibres are actually
required to be able to read 20/30 (6/9).
Table 1.1 shows the pathological and physiological factors
that can limit visual acuity. This process can be influenced by
physiological and pathological factors anywhere along this
pathway.
Background illumination alters the level of retinal adaptation.
Low levels of light stimulate the rod system; the receptor density
and level of retinal integration of this system are less than that of
the cones and consequently acuity is also low. At high levels of
illumination the cone system is stimulated and acuity is maximal.
To obtain the best visual acuity illumination should be in the
optimal photopic range. Because of the effect of reduced retinal
illumination from lens opacities in patients with cataract may be
seeing in the mesopic to low photopic range where the acuity is
proportional to background illumination. In these patients, an
increase in the ambient lighting will give them better vision
provided that light scattering by the cataract does not counter
this.
Pathological factors Physiological limitations
Media opacities Optical aberrat ions
Cone receptor loss or dysf unction Cone receptor spacing and
integrat ion
Damaged to anterior visual pathw ay
Dysfunction of visual cortex,
secondary cortical areas
 VISUAL ACUITY

20/10 Scotopic Mesopic Photopic

>- 0"1
.~ c
:::> 20/ 15 ·..=;
u ~

"' 20/20 ~
"'~ <0
·o ....
20/25 ~
Fig. 1.1 As high-resolution central vision depends on cone
> 20/35
<;::
·-e
ro ·"'"'
:;.,
"0
receptors any reduction in cone function will greatly compromise
20/50 =o0 c
ro
acuity. This graph shows visual acuity plotted against background
20/100 0 Q)
illumination. The best acuity in the scotopic (rod-sensitive) region
20/200 1,9 2
of the curve is 20/200 (6/60), whereas under photopic (cone-
-6 - 5 -4 - 3 -2 -1 0 2 3 4 sensitive) conditions acuity can increase to approximately 20/15
(6/5). The curve flattens once optimal conditions are reached and
Log intensity (millilamberts)
background illlumination
then reduces owing to the effect of dazzle.

- Cones -Rods - Acuity 20/10

180
E
E 160
V\
(1)
&
V\ 140 20/15 <
v;·
c ~ c
0 (1)
uO. 120 "'
~:§' 100 20/20
"';::;:,..,c
0 c
cc:"'
V\ 80 20/25 '<
::::>

~
0
60 20/35
.::.
40 20/50
20 20/100
20/200

70 50 30 10 0 10 30 50 70 90
Tempora l Nasal Fig. 1.2 Visual acuity and cone and rod density plotted against
Degrees from fovea degrees from the foveal centre. There are no blue cones at the
fovea.

MEASUREMENT OF VISUAL ACUITY

Visual acuity is usually measured at a distance of 6 metres nodal point of the eye; it depends on the size and distance of the
(20 feet) to eliminate the contribution from accommodation. It object from the eye. The normal limit of resolution is 1 minute of
should be performed on each eye in turn without and with full arc but some individuals see better than this possibly due to a
refractive correction. Acuity is usually measured at high contrast. finer cone mosaic, better image processing in the retina or cortex,
The visual angle refers to the angle subtended by an object at the or fewer optical aberrations.

Snellen E Landholt ring

Fig. 1.3 Each individual component of a letter or shape must be

resolved to be identified. A letter 'E' viewed at the limit of
resolution (20/20, 6/6) subtends 5 min of arc, each individual
component subtending 1 min. The same principle is used in the
construction of the Landholt rings.
OCULAR EXAIVIII'JAIIOI'J

Fig. 1.4 Acuity charts are constructed with rows of letters of

different sizes. Letters are constructed so that they subtend the
same visual angle at a specified distance of up to 200 feet. Thus the
largest letter should be resolvable by a normal eye from 200 feet
( 60 metres) away and the smallest at 20 feet ( 6 metres). If the chart
is read at 20 feet a normal eye will read all the letters. Any loss of
resolution will result in the eye being able to read only larger
letters. The test distance is then divided by this line and is
expressed as:
60 metres
test distance/smallest line of letters read = visual acuity
0 20 40 60 80 100 200 feet An acuity of 20/40 means that the patient sees at 20 feet what a
Distance normal eye would see at 40 feet. It can also be measured in
metres (6/12), as a decimal (0.5), or as the angle subtended by
the smallest gap of the letter (2 min of arc).

H c E
AL 00 1113
TNC 000 IIIEI11
OLHA E3111bl
ECTNO
ooco 111EP1111!1
Fig. 1.5 Professor Snellen developed his chart in Utrecht in
1863. The Snellen chart is accepted as the standard chart for
clinical practice but it has some problems. Some letters are more
CLOHNA ocooo :51bi:51EIIIbl legible than others; for example, 'L' is easier to read than 'E'.
A E L 0 H 0 T llJ Ill E 3 Ill llJ E Patients must also be literate. Modifications to avoid this include
0 0 0 0 0 0 Landholt rings where the patient must identify the orientation of a
H T H E L A 0 0 3 E IJJ JTI IJJ E 3 JTI
A E 0 0 H N T L gap or illiterate charts where a cutout letter 'E' is matched with the
c 0 c 0 0 0 0 ITI :3 E W 3 Ill W E
same letter in different orientations.

feet
20/200 6/60

c z
Fig. 1.6 Snellen charts also have the defect of different numbers

N K 0 of letters on each line causing crowding phenomena and

nonproportional spacing between letters and lines . Furthermore,
the measured range does not extend far enough into low visual
160
R H s D K 0.9 acuity ranges. The Bailey-Lovie, Early Treatment Diabetic
Retinopathy Study (ETDRS) or LogMAR (log of minimum angle
of resolution) chart overcomes these problems. It gives a
125
D 0 v H R 0.8 progressive linear assessment of acuity and has become the
standard for clinical research. Each row has five letters with a
100 c z R H s 0.7 doubling of the visual angle every three lines. It is read at 4 m and
covers Snellen equivalents from 20/200 to 20110 . Each letter read
80 0 N H R C 0.6 (6/24)
is scored as -0 .02 and each row as -0.1 (5 x -0.02). Visual acuity is
63 D K S N V 0.5
given as the log value of the last complete row read plus -0.02 for
50 Z S 0 K N 0.4
40 C K 0 N R 0.3 (6/12)
each letter read on the row beneath. An acuity of 1.0 equates to
32 S R Z K D 0.2 20/200, 0.3 to 20/40, and 0.0 to 20/20. This contrasts with Snellen
25 0.1
20 00 (6/6) charts in that the lower the value for visual acuity, the better the
16 -0 1
VISIOn.
 VISUAL ACUITY

MNREAD'" ACUITY CHART 1

M size Snellen logMAR

My father asked me lor40cm (16inches)

4.0 to help the two men 201200 1.0

carry the box inside

Three of my friends
3.2 had never been to a 20/160 0.9

circus before today

My grandfather has
2.5 a large garden with 20/125 0.8
fruit and vegetables

He told a long story

2.0 about ducks before 20/100 0.7
his son went to bed

My mother loves to Fig. 1. 7 Traditionally near vision testing is done using the
1.6 hear the youn g g irls 20180 0.6
sing in the morning appropriate reading correction with a chart of different font sizes.
The young boy held
This has, however, no physiological basis and a more scientific
1.3 hishandhightoask
questions in school
20163 0.5
method is to use a reduced LogMAR chart such as the MN Read
1.0
Mybrotherw•nled
agla.,;ofmi lkwith
card at a standardized distance and illumination. The text in this
hi• cal<~ alter lu och 20150 0.4
chart conforms to LogMAR principles; in addition each paragraph
0.8
..,, ...... ""',
ldu ... ............
• by ........... .
..., 20140 0.3 is standardized for length of words, sentences and grammatical
0.6 20/32 0.2 complexity. It also allows for reading speed to be measured.
0.5
0.4
20/25 0.1
Patients need to read at 80 words a minute or better to have
20120 0.0

------------------- "'-"·'
-------------------- ii'
""'
-··_., functional near vision at that size of print.
© 1994, Regents of the University of Minn esota, USA. MNREAD™
~j:j
0CopyrigMI994, AegentsollhiUnivertiryol~ . MNAEAD"'3.1-13600
3.1-1 /3600.

TESTING ACUITY IN CHILDREN

Visual acuity assessment in children presents particular
problems. Good results can be achieved only with time and
patience and by selecting the right test for the age of the child.
These include qualitative tests such as the child turning to fixate
a face or light, suppression of optokinetic nystagmus following
rotation or objecting to occlusion of one eye. While
semiquantitative measurements are available, for instance
picking up 'hundreds and thousands' sweets or following small
balls quantitative tests are most informative. For infants forced-
choice preferential looking or visual evoked potentials (VEPs)
can be used; both give different results. Older verbal children can
use picture cards (Cardiff cards, Kay's pictures) and from the age
of three may manage matching letter tests (e.g. the
Sheridan-Gardiner test; see Ch. 18). Caution is necessary when
using Snellen charts with single letters because of the
phenomenon of 'crowding'- being able to see single letters more
easily than rows of letters - which can overestimate true acuity.

Fig. 1.8 With preferential viewing techniques the child is shown

two cards: one has a grating, the other has the same uniform
overall luminance. If the child can distinguish the grating, he or
she looks at this 'preferentially' - presumably because it is more
interesting.
By courtesy of Professor A Fielder.
 20/12

20/25 :v
>.
.<::: 20/50
:::l
v
"'c 20/100
~
Qj
c
Vl
20/200

20/400

20/200
0 Fig. 1.9 What is known of the development of visual acuity with
0 2 4 6 8 10 12 22 24 age depends to some extent on which method of testing was used
Age (months) in studies as VEPs, optokinetic reflexes or preferential looking
techniques all give different results . The latter is the most
- Visually evoked potential commonly used technique; it shows that infants do n ot reach adult
- Optokinetic nystagmus levels of acuity until 2-3 years of age .
- Preferential looking By courtesy of the Editor, Survey of Ophthalmology 1981,· 25: 325-332.

PHYSIOLOGICAL LIMITATION OF ACUITY

The physiological limits of visual acuity are essentially set by the
sources of error in the system uncorrectable by standard
refraction . Light rays passing through the eye are degraded by
inbuilt optical aberrations, thereby increasing the blur at the
margins of the images. This loss in edge contrast reduces the
resolving power of the visual system. Apart from refractive error
(sphere and cylinder), the main optical factors are higher-order
aberrations, chromatic aberration and diffraction . Glare
disability is produced from forward light-scatter from the ocular
media and opacities. It casts a veiling luminance over the macula,
reducing image contrast. A good clinical example is posterior
subcapsular cataract where acuity is relatively well preserved but
the patient has a disabling glare in bright light.

Fig. 1.10 (Top) Spherical aberration. The refractive surfaces of

the eye have more effective power at the periphery than at the
central paraxial zones. This causes the edge of an image to b e
blurred by the resulting 'line spread'. Spherical aberration increases
with pupillary dilatation . The eye n orm ally has a positive spherical
b
aberration (see Ch. 11 ).
Chromatic aberration. The refraction of light varies according
to its wavelength. Short wavelengths (blue) are refracted more than
longer wavelengths (red), polychromatic white light is focused as a
coloured blur, and the contrast at the image edge becom es
degraded by coloured fringes. (This aberration is used to clinical
advantage in the duochrome test to prevent overaccommodation in
myopes.)
-0.25 to +0.25d
Diffraction. This becomes important with pupil diameters of
c less than 2 mm. Light projected through an aperture passes
through the centre but is absorbed and retransmitted at the edges.
The wavefronts of retransmitted light then cause interference
patterns that increase the line spread of the image focused beyond
the pupil.
As larger pupillary apertures increase chromatic and spherical
aberration and smaller diameters increase diffraction the best
compromise is achieved with a pupil diameter of 2.4 mm.
 VISUAL ACUITY 7

WAVEFRONT ANAlYSIS

Wavefront analysis plots the total optical aberration of the eye.
The low-order aberrations of sphere and cylinder can be
corrected by simple optics; higher-order aberrations cannot be
Sturm's Conoid
corrected by routine refraction. These used to be referred to as
'irregular astigmatism' and, in the case of irregular corneal
astigmatism, can be corrected only by wearing a contact lens.
Wavefront analysis allows detailed analysis of these aberrations; it
has become important in understanding patient dissatisfaction
following refractive surgery and, by correcting aberrations, offers
the possibility of supranormal vision. This has yet to be achieved.

Fig. 1.11 With regular astigmatism, light is brought to focus at

two points. Sturm's conoid is the circle of least confusion that can
be brought to focus by a sphero-cylinder combination. With the
imperfect optics of the eye light is bought to focus in an irregular
manner. This caused by higher-order aberrations which can be
Blurred focus demonstrated by wavefront analysis and described mathematically
by Zernicke polynomial curve fitting equations.

Lenslet array

/P<eollel "''

Perfect optics

+-
0 0 0 0 0
0 0 0 0 0 Regu lar array and
0 0 0 0 0 wavefront
0 0 0 0 0
perpendicular
0 0 0 0 0
to visual axis

Fig. 1.12 In a perfect optical system rays of light exiting the eye
from a spot projected on the fovea should exit the eye parallel to
the visual axis with a wavefront perpendicular to the visual axis.
If these exiting rays are imaged through an array of lenslets
their displacement from parallel to the visual axis is a measure
of the optical errors in the visual pathway. This can be done
with a Shack-Hartman aberrometer, a technique that has long
been used in astrophysics. Light coming to focus in front of the
Imperfect optics
0 0 0 0° 0 plane is 'advanced' and that behind the plane is 'retarded'. In
0 0 0 0 0
Irregular array and
0 0 0 wavefront distorted the eye most aberration is produced in the cornea.
o o oo
0 0 0 0 from perpendicular
0 0 0
to visual axis
 Common names Radia l order

Piston c=:>
0
0

Tip, Tilt (Prism)

Astig matism (3, 5),

Defocus (4)
2
3 4 5
Fig. 1.13 The wavefront deformation from a plane perpendicular
Coma (7 , 8)
Trefoil (6, 9) 3 to the visual axis can be expressed in terms of a m athematical
equation consisting of a series of polynomials. These Zernicke
6 7 8 9
polynomials describe an increasing cascade of aberrations. Low-

~
Spherica l abberation order aberrations (first and second order : sphere and cylinder)
(12) 4 account for m ore than 90 per cent of refractive error in a normal
14 eye . Third order is coma and fourth order is spherical aberration .
Spherical aberration is the clinically most important after sphere
Secon dary coma
(17, 18)
00
15 16 17 18
~~ 19 20
5
and cylinder. Higher orders account for less and less of the
aberration. The system becomes extremely complicated as some
aberrations can cancel out others; treating one aberration in the
absence of all can therefore actually make vision worse.

CONTRAST SENSITIVITY

The eye can detect ob jects b y responding to the differing levels
of luminance between a target and its background. This is
defined in terms of the maximum and minimum luminance at
the detected edge .
Target luminance- background luminance
Contrast =
Target luminance +background luminance
Standard visu al acuity tests measure acuity under high contrast
conditions but do not tell u s anything about visual performance
under different circumstances such as driving at night or reading
in poor light which are often m ore appropriate to daily life and
cause clinical symptom s. It is thus possible for patients to retain
good Snellen acuity but have reduced contrast sen sitivity at lower
levels of illumination. Contrast sen sitivity testing is of particular
importance in assessing the effect of refractive surgery on visual
performance. It can be measured at either a fixed target size with
varying con trast or over a range of target sizes (spatial
frequencies) and contrast to d erive a contrast sen sitivity curve,
which is an extremely useful way to assess overall visual
performance. There are a number of different ways to test
contrast sensitivity; they fall into two groups - either
differentiating bars, stripes and gratings or, alternatively, letters
against a background. L etter tests usually produce a better
performance than gratings.

Fig. 1.14 Sine wave gratings can be used to assess contrast

sensitivity and spatial frequency simultaneously. The patterns can
be generated electronically on a television screen or graphically on
a test card or chart. The spatial frequency of the stripes increases
along the horizontal axis from left to right (that is, the stripes get
thinner and closer together) and the contrast decreases on moving
up the vertical axis. As the frequency of the stripes increases to the
minimum resolvable acuity (30- 40 cycles per second or 1- 0.5 min
of arc), there is insufficient contrast to distinguish the stripes from
the background. As a result the highest resolvable frequencies can
be seen only at high contrast (this equates to standard visual acuity
tests). Beyon d this point the grating appears as uniform greyness.
As the spatial frequency decreases there is insufficient contrast to
distinguish the stripes from the b ackground illumination.
By courtesy of M r JW H owe.
 CONTRAST SENSITIVITY

~
...,~

I
c 100
0
u
01
c
·v;
ro
~
u
Q)
Cl
Fig. 1.15 If grating visibility is plotted on a graph, the axes being
contrast and spatial frequency, a bell-shaped curve known as a
contrast sensitivity curve is formed. At the apex of the curve the
10 subject reaches their highest level of sensitivity at low contrast
1.5 3 6 12 18 36 levels and changes in contrast of 1 per cent or better can be
detected. The graph shows the curves of a normal eye compared to
Increasing spatial frequency the fellow eye with optic neuritis. Although the affected eye has
Normal eye (cycles per degree) good acuity it will have poorer performance in low-contrast
Optic Neuritis conditions such as poor lighting.

Pelli-Robson contrast sensitivity

Low contrast VA

High contrast VA Fig. 1.16 This shows how the different measurements of visual
acuity and contrast acuity interrelate. High- and low-contrast
0.1 10 100 visual acuity charts measure a change in spatial frequency at a
fixed contrast (horizontal) and the Pelli- Robson chart measures
Spatial frequency (cpd)
contrast sensitivity at a fixed spatial frequency (vertical).

H s z s D N
c K R Z v R
N D co s K
OZKV H z
N HON R D
V R co v H Fig. 1.17 The Pelli-Robson chart is a commonly used method of measuring contrast
sensitivity at a set spatial frequency of 6 six cycles per degree. This corresponds both to the
0 spatial frequencies most important in daily life and to the maximum contrast sensitivity of the
eye. The chart is viewed at 1 metre under standardized illumination.
 COLOUR VISION

The perception of colour arises from the different cone receptors
that are maximally sensitive at three separate wavelengths: red
(protan), green (deuteran) and blue (tritan). Light of different
wavelengths stimulates each of the cone populations to a
different degree so that colours within the visible spectrum arise
from their own specific pattern of cone stimulation. Colour
brightness (luminosity) and saturation (amount of white light
present) are other properties detected by the eye that must be
taken into account in colour testing. As colour vision depends on
cones it is a property of photopic central vision.

80 8

N 70 7
E
E OJ
;:;;- 60 6 c
0 Ill
(">
>-
+J 50 5 0
:::;)
·v; Ill
c 0..
QJ
'0 40 4 Ill
:::;)
QJ V>
c ;:;:
0 '<
u 30 3
c 0
QJ -"!
~ 20 2 3
Cl
3N
::a
QJ
c:r::: 10

0 0
- 10 - 8 - 6 - 4 - 2 0 2 4 Fig. 1.18 Colour perception is maximal in the centre of the
6 8 10
retina but extends out to 25- 30° of the visual field . Beyond this,
Nasal Temporal
red- green perception disappears and then, in the periphery, all
Eccentricity
colour perception is absent. There are no blue cones in the fovea
- 8/uecones Red/green cones and they are less numerous than red-green cones elsewhere in the
macula.

Cones Blue sensitive

1.0 Green sensitive
Red sensitive

0.8
QJ
u
c
.c"'
0 0.6
B
"'0
'+-

QJ
Cl
0.4
c
~
u"'
0.2
Fig. 1.19 Investigation of the spectral sensitivity curves of the
human retina shows peaks at about 440 nm (blue), 540 nm (green)
0 and 570 nm (red). This diagram illustrates the way in which the
ranges of wavelength sensitivities of cones overlap; the curves have
a gentle slope on the short wavelength side and a rapid fall on the
400 500 600 700 side of long wavelength, that is, towards red.
Adapted from Pyman GA, Sanders L, Goldberg B. Principles and Practice
Wavelength (nm)
of Ophthalmology. © 1979 Elsevier.

ABNORMAL COLOUR VISION

Abnormal colour vision can either be congenital or acquired; red- green axis whereas macular damage affects the blue- yellow
acquired causes include macular and optic nerve damage. axis. There are many exceptions to this rule, such as glaucoma
KoHner's rule states that optic nerve disease tends to affect the and autosomal dominant optic atrophy, which affect the

blue- yellow axis; and Stargardt's disease, which primarily affects
the red- green axis. Patients who have abnormal cone populations
are not able to match some colours visible to a patient with
normal anatomy but have a normal ability within other spectral
areas. The most common type of colour deficiency is anomalous
trichromacy in which the person has three cone populations but
is deficient in one of them. Thus with protanomaly the person is
deficient in red cones and needs excess red to match yellow;
deuteranomaly requires more green. Dichromats have only two
cone systems and thus cannot distinguish certain colours.
Protanopes have absence of red cones, deuteranopes green
cones. These anomalies are transmitted on the X chromosome
and affect about 7 per cent of Caucasian males. Tritanomaly is
very rare. These patients have difficulty in distinguishing
turquoise blues and greens or yellows and pinks from one
another. Achromatopsia is the complete absence of cones. These
patients can distinguish colour only in terms of brightness; they
COLOUR VISION 1
have photophobia and poor vision. All patients with congenital
colour defects have normal fundi.
Several clinical tests exist for the assessment of colour vision.
These include pseudoisochromatic test plates, hue-matching
tests and anomaloscopes; the former are the quickest and easiest
to use. The most common is the Ishihara test for red- green
defects; other types are the Hardy-Ritcher- Rand (HRR) series
or the City University System which have the important
advantage of testing the blue-yellow axis as well as red- green. If
pseudochromatic plates are to be used properly in testing cone
function they must be viewed at 75 em in controlled white light
and luminance conditions with appropriate refractive correction.
Hue-matching tests, such as the Farnsworth- Munsell test, are
more accurate but more time consuming. Testing colour contrast
sensitivity with computerized systems is a sensitive, reliable and
valid research tool.
Fig. 1.20 Ishihara plates were originally designed for assessing
congenital red- green confusion but are often used clinically to
assess colour loss secondary to optic nerve damage. The test
consists of plates with a matrix of dots arranged to make either a
number or a line that can be traced out. The dots making up the
numbers are visible to people with normal red- green colour vision,
but are confused with adjacent colours by those who are red-green
deficient. The coloured dots are designed to be isochromatic so
that the dots making up the letters cannot be perceived by contrast
difference alone. A test plate containing the number 12 composed
of high-contrast dots is shown at the start to ensure that the
subject has sufficient visual acuity to read the numbers. The test
plate (a,b) and a trial plate (c,d) are illustrated, with and without a
green filter. With the green filter, the test number almost
disappears, but the trial plate number is still easily visible as the
plate can be perceived by contrast rather than colour
discrimination.
Fig. 1.21 Despite its name, the Farnsworth-Munsell 100 hue
test actually consists of 84 coloured tiles arranged in four separate
trays. In the test the difference between the tiles is graded so that
there is one unit of 'just noticeable difference' between them. Each
of the four trays covers a different range of the colour spectrum.
Trays of tiles are taken one at a time and jumbled. The patient
then views these under a standard white light and rearranges the
tiles in chromatic order between the two reference tiles placed at
each end of the tray. The misalignment of the tiles from their
correct position in the chromatic series is then scored and marked
on a standard chart; the greater the displacement, the higher the
score. The test is considerably faster when using computerized
reading and plotting.
O C ULAR EXAIOIIIGAJ 101\1

Fig. 1.22 In a normal person only one or two tiles would be misplaced, and the score sheet would appear as a small circle. In the
different colour anomalies, however, the chart becomes distorted along a particular axis. The axis of distortion is typical for a particular
colour deficiency; examples of the axis for protanomaly (a), deuteranomaly (b), and tritanomaly (c) are shown. Patients with nonspecific
acquired colour defects usually make errors in all parts of the wheel.

Fig. 1.23 A newer variant of the test, the D-15, uses 15 tiles and
is easier and quicker to use.
By courtesy of Mr C.J. Hunt.

' 4
2 \3
~:~......._-

:~
...... • ::>

"-\/'~
"
.~. --------~~~\;; 8 8
,,J,-f

15' 14 · ; \

!13 \,
Normal vision 12 11
-no errors
4

8
Fig. 1.24 This shows the normal result. Patients
with congenital colour defects have difficulty in
matching tiles along a particular axis.
Adapted from Pyman GA, Sanders L, Goldberg B. Principles
and Practice of Ophthalmology. © 1979 Elsevier.

VISUAL FIELD TESTS
The visual field is the area in space perceived by the eye
classically described byTraquair as 'an island of vision in a sea of
darkness'. The sensitivity (or threshold) for stimulus detection
varies throughout the visual field and, in the absence of
pathology, depends largely on the number and function of the
ganglion cell receptive fields at any given point. Lines (isopters)
oo
Expansion of visual goo
field with increasing
ta rget size
MEASURING VISUAL FIELDS
Visual fields are assessed to localize lesions in the visual pathway,
document their severity and measure progression with time.
Qualitative or quantitative techniques can be used. Perimetry
may be either kinetic or static, the latter manual or automated.
Kinetic perimetry requires a moving target to be detected
whereas static perimetry requires perception of a stationary
target of varying brightness. Occasionally, a stationary target
cannot be perceived whereas an equivalent moving one can; this
is known as the Riddoch phenomenon. While kinetic fields have
the advantage of producing a readily interpreted 'map' of isopters
static fields produce numerical data at a set of predetermined
points that can be handled statistically. Changes within the field
can be followed more precisely and this has proven to be very
useful in the management of glaucoma. Computer-assisted static
perimetry, complex testing strategies and data analysis, such as
VISUAL FIELD TESTS
connect points where a target of the same size and brightness is
first perceived on kinetic perimetry, that is, points of equal retinal
sensitivity. As with acuity and colour vision a person's visual field
is altered by background illumination as this affects retinal
adaptation and receptor function.
Fig. 1.25 The plot of the visual field isopters can be represented
in a three-dimensional form called Traquair's Island, in which the
isopters appear as contour lines on the island. The height of any
point on the island is proportional to the sensitivity of stimulus
detection at that point and thus is inversely proportional to the
threshold. The topography of the island is not static but varies with
retinal adaptation. Under mesopic conditions, the gradient of
sensitivity away from the central areas is much more gentle than
under photopic conditions, where the peripheral retina is
desensitized and foveal function is more acute. For this reason, it is
important that comparisons of the visual field are made under
standardized conditions of retinal adaptation.
comparison with age-matched controls and the calculation of
reliability indices makes it easier to store and analyse sequential
data in order to detect disease progression. A major advantage of
computer automated over manual kinetic perimetry is that it is
less operator dependent. Disadvantages relate to its complexity,
a considerable patient learning curve, patient fatigue and normal
fluctuations in this field over time.
The results of visual field testing depend on the stimulus used
(size, colour, brightness) and the background illumination. It is
therefore important to be aware of these values when comparing
different field tests. Other factors that can affect test results
include patient fixation and concentration, test duration,
refractive errors (for the central field only), media opacity (e.g.
cataract), miosis and objects accidentally obstructing the field
(e.g. rim of glasses, upper lid).
 Fig. 1.26 The simplest way to test the visual field is a
confrontation technique. The examiner sits opposite the patient at
a distance of approximately 1 m. The patient and examiner cover
opposite eyes with their palms so that the uncovered eyes have
mutually congruent fields. The examiner then introduces a test
target into the field (fingers, hand, red bottle cap) until the target is
perceived by the patient (kinetic perimetry). The patient's and
examiner's fields should be congruent, so the presence of a defect
is noted by the absent patient response when the object is visible in
the examiner's field. A red target is especially useful for detecting
early neurological defects in the central 30° of the field. This is
because the retrobulbar pathways are particularly sensitive to red,
being concerned mainly with macular vision. If the patient is asked
to compare the quality of colour between quadrants (static
perimetry) very early defects, such as a bitemporal hemianopia, can
be detected subjectively. With practice, a confrontation field can be
obtained from almost any patient and produces helpful localizing
information.

Fig. 1.27 The Goldmann perimeter is usually used for kinetic

perimetry but can be adapted for some basic static perimetry. It
consists of a hemispherical bowl that is uniformly illuminated and
on to which target lights of varying size and brightness are
projected. Target size, brightness, colour, background illumination
and fixation are all controlled. The patient sits at the machine with
the eye to be tested fixed on the centre of the hemisphere. Fixation
is checked by an observation telescope mounted at the central
fixation point. The target lights are then introduced by the
projector into the visual field of the patient while a pantograph arm
moves across a standard recording chart at the rear. As the patient
signals perception of the target the examiner marks the chart and
eventually plots the isopter to the particular target. The test is
usually undertaken at several isopters of target size and brightness,
thus producing a kinetic field that demonstrates the area and
density of field loss. A static assessment can be made by flashing
the target light within the appropriate isopter. Goldmann fields
have the disadvantage of being somewhat examiner dependent but
they do assess the full field area making them useful for assessment
of neurological deficits.

Fig. 1.28 A typical visual field as plotted on a Goldmann

perimeter. The visual field, which is marked off in degrees from the

.., . •
fovea, is not circular but displaced laterally and downwards. The
Relatmtens upper and medial limits are approximately 60°, the temporal 100°
"' 4 3 2 1
and the inferior 75°. In the temporal field the exit of the optic
0
nerve is marked by the blind spot, 5.5° in height and 5° wide, the
,
II
centre being about 15° from the centre of foveal fixation. The
Ill prominence of the brow and the nose may cause artefacts in the
nasal and superior visual field that the examiner must be aware of
v
and able to correct.
 VISUAL FIELD TESTS 15

Fig. 1.29 The most commonly used computer-assisted static perimeter is the
Humphrey analyser, shown here. Static targets of fixed size but variable intensity are
presented randomly at different retinal coordinates within a bowl perimeter of
constant photopic background illumination (21.5 asb). These coordinates have been
selected for their discriminatory potential in glaucoma. Fixation is automatically
monitored and displayed on a television screen to the side. Throughout the
procedure the software program checks and rechecks that fixation is maintained and
scores how well the patient fixates. To test for false-positive results the stimulus is
withheld when the machine audibly indicates stimulus presentation. False-negative
findings are assessed by re-examining a number of tested areas with a suprathreshold
stimulus. The duration of the test depends on the number of repetitions at each point
and the speed of the patient's response. To perform well the patient needs to be
familiar with the test - a learning curve is often demonstrated. The Octopus machine
is another computer-assisted static perimeter using a mesopic background
illumination ( 4 asb).
Static field analysers measure the threshold intensity for stimulus detection at
each point. The human eye needs about a 10 per cent increase in brightness to
discern a stimulus against background luminance. The intensity of luminance of the
target is measured in apostilbs and converted to a logarithmic scale (decibels). 1 log
unit of retinal sensitivity is 10 dB, with a range from 0 to 40 dB. To measure
threshold the Humphrey analyser increases the target luminance in 4-dB steps until
detection and then decreases it by 2 dB to define the threshold. Values are given in
decibels of attenuation and correspond to retinal sensitivity. Thus, the higher the
value, the greater the attenuation of the stimulus and the more sensitive the retina.
Full threshold testing is time consuming and difficult for some patients so a variety
of faster test strategies exists. The most widely used is the SITA program (Swedish
Interactive Thresholding Algorithm). Suprathreshold programs can be used for
screening. These detect variation from the age-matched norm and do not calculate
absolute values at each point.

F!XIITIGH ~OHITOR: BLIHDSPOT STiftULUSllll,lllm PUPilDIRmER: om:J0-81-2894

FIXIITIONTIIRCH:CEH TRRL BRC~GROUHO: 31.5 RSB VISURLRCUIT'Il
FIXATiOI!LOSSES:IlllJ STRRTECY:SITR-FRST RX:+2.590S DC X AGf:73
~ALSE POS ERRORS: 8X
flllSEH£GmORS: SX
TESTDURmOH:~:57 Chart A Chart B
FOVEA: OFF
18 <8 (8 17

17 21 24 21 28 18

22 IS 2& 27 22 22 19 18

23 11 (8 13 9 (8 (8 7

<e 13 <e <e e <e

<e <e <e <e Fig. 1.30 Computer printout from a Humphrey visual field
analyser showing the location and sensitivity of the 54 tested
Chart C Chart D
retinal loci in the 24-2 program. Chart A represents the actual
~~~· ~~~·
-1e -s -~ ·7 -s -te -s -J e -4 -s -7 retinal threshold at each locus in decibels. Chart B shows this as a
·S -9-4-3-8-8 ·11·18 -3 -see -5 -s -7-7
-1-1-3 ·S -8 · 9 · 9 -4 2 z e -J -5 -s -s CHT
OUTSIOEHCRnRLWITS
grey scale for rapid interpretation. Chart C shows the total
·2 -2 -J -27-33-27-29 -4 2 2 II -24-29-23·25
-7 ·19 · 33-19-23-33-32-22 ·3 -IS-30·15-28-38-29-18 deviation. This is the difference at each point from an age-matched
-32-17-33·33·38·31 ·28·13-29-29·27·28
·31·31-31-38 -28 · 28·28-27
~0 -15.2~ DB P < 8 .5~ control; the lower chart converts this to a statistical probability.
PSO 12.41 DB P < 8.5~

....
TOTRL PATT£RH Chart D adjusts this to compensate for any generalized depression
OEVIRTIOH OEVIATIOH
across the field (e.g. from cataract or miosis), thereby defining
....
••••
• 0: ;; • • • ~ . :: ~ M focal loss more clearly. Average numerical 'global indices' for these

...... .
~ . ;; ;; ~ :Ill; :Ill;. :Ill;
Ji ~ ••• ~ deviations are also given as mean deviation (MD) and pattern
Ji
~
:; • • • •
••••
• •••••• standard deviation (PSD). In addition, reliability indices are given
••••••
• • •• • ••••• on the printout. These are fixation losses, false positives (trigger-
:; ( ~~
• ••• happy patient) and false negatives (inattentive patient). This is
~ ( 2~

Jj ( ~~
assessed by measuring the threshold twice at ten predetermined
• ( 9.5~ points .
OCULAR EXAMINATION

Threshold (dB)
I
22 22 23 31
30 36 \ 12 0 0
24
19 10 0 0 0

26 10 0 0

Deviation

30°

Fig. 1.31 Glaucoma has been shown preferentially to affect the large-diameter optic nerve axons (magnocellular pathway). Several new
tests are designed to exploit this and have considerable clinical potential. Frequency doubling perimetry projects a low frequency (1 cpd)
sine wave grating into a sector of the retina. The grating is moved at high temporal frequency until the patient gets the sensation that the
frequency of the grating has doubled (i.e. there are twice as many bands); this is the endpoint. The test is rapid and sensitive, can be done
in room light, and patients prefer it to conventional perimetry. Another new test is SWAP (shortwave automated perimetry) which uses a
blue target on a yellow background. This test is very sensitive in detecting glaucoma defects but is affected by cataract.

Blurring and
v distortat ion
v
v
' ~

Fig. 1.32 The Amsler grid is a field test that assesses the central
10° of vision qualitatively. It is an effective and rapid method for
detecting macular abnormalities that cause blurring or distortion.
The test is monocular. The patient holds the grid 25- 30 em away,
fixing on the central dot and draws around the area of abnormality.
Sequential grids are very useful to follow changes.

OCULAR EXAMINATION
SPECULAR MICROSCOPY
Fig, 1.34 Specular reflection is used as the basis of specular
microscopy to view or image the corneal endothelium and other
intraocular surfaces such as the surface of an intraocular lens, in
this case showing foreign body giant cells on the IOL.
CORNEAL TOPOGRAPHY AND KERATOMETRY
Measurement of corneal curvature is essential for the fitting of
contact lenses, assessment of the eye for refractive surgery,
correction of excessive astigmatism and the correct calculation of
intraocular lens power. It is also useful for monitoring corneal
diseases such as keratoconus. Measurement is based on the
principle that the anterior surface of the cornea acts as a convex
mirror reflecting a small portion of incident light to form the first
Purkinje image, which is visualized to form a map of isopteric
power. It is important to realize that corneal topography
VISUAL FIELD TESTS
Fig. 1.33 When a beam of light traverses a heterogeneous optical
medium most of the light is transmitted, but at each optical
interface a proportion of light is reflected.
simplifies corneal refraction as it assumes that refraction takes
place at a single interface with a single refractive index. In reality,
the anterior corneal surface has a curvature of +49D, the
posterior surface of -6D, with variations in the refractive index
across the corneal tissue layers. These factors become extremely
important after laser refractive corneal surgery which changes all
three parameters. This is the reason why standard biometry for
intraocular lens calculation is unpredictable after laser surgery.
O CULAR EXAIVIINAI ION

Fig. 1.35 Corneal topography. The photograph of the reflected

image and its distortions are analysed by computer to produce a
topographical map of the anterior corneal surface giving
quantitative information on the corneal curvature. From this,
corneal astigmatism and its meridians can be calculated.
© 1995- 2002 Bausch & Lomb Inc.

0.92 Pachymetry . Axial Power

Keratometric
Thickness 58.00
56.00
54.00
52.00
50.00
48.00
48.00
44.00
42.00
40.00
38.00
36.00
34.00
N
N T 32.00
30.00
28.00
26.00

'" OS
... 1.0 0 Color Steps 210
Copyright 1~2002. Bausch & lomb Inc .
20 mic Color Steps %70 OS AC-X-CMS003
Copyright 199&2002. Bausch & lomb Inc.
AC.X.CM003

Fig. 1.36 Topographic printouts are colour coded. By convention steep

areas are coloured red and flat areas blue although the actual dioptric values
for each colour are not standardised between instruments. Most normal
corneas remain within the yellow-green spectrum of the scale. Common
patterns seen include a bow tie pattern in astigmatism and a central steep
island in keratoconus (see Chapter 6). This eye has an old scar inferio-
nasally. The pachymetry map shows this area is thinned. Topography shows
this area is slightly ectatic with a steeper curvature causing irregular
astigmatism.
©1995- 2002 Bausch & Lomb Inc.
 OCULAR EXAMINATION

60 =43. 57 D
' = 0. 0 °
135 .15 = 0. 0 °
= 0. 00 mm
.30
0

15Q 0
l.OQ
CORNEAL
OQ.
OQ. STATISTICS
1.0Q.
65... A5 .OQ
1.0Q.
SRI:-0.1 SAI:O. l4
I. OQ PUA: 20115-20120
OQ Si11 K: 44. 6 x87 1
S.OQ_
-{) G.OQ. _ 42. 2x!77
7. ~ Min K: 42. 2xl77
6.00.-
Cyl: 2. 40
95' ~~
3. 0Qi'
1. ~

21() 0
0 '330 ··~
0. ~
.OQ_

0 2~5 °

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0
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0

300 .OQ.
Z.()Q
PU!lllx,y;-D.231, o.
I
255 270 285 OiopH;r~

Fig. 1.37 This technology is essential in the assessment of refractive corneal surgery. These charts show a cornea before excimer laser
ablation (left). The isopters are graded in lD steps and show with the rule astigmatism of 2.4D. After photoablation (right), the
astigmatism has been reduced to 1.8D with the rule and there has been a reduction of myopia of 2.5D.
By courtesy of Mr D O'Brart.

Fig. 1.38 Corneal curvature is routinely measured

before cataract surgery to calculate intraocular lens
power. Although this information can be obtained from
detailed topography only the curvature of the central
3 mm of cornea is important for this and this can be
obtained from a simplified topographic technique or by
manual keratometry. The spherical power in the axis of
the two regular meridians can easily be measured using
a basic keratometer of which there are two types
(Schiotz and Helmholtz). The former uses an object of
varying size and the latter an image of varying size.
The Schiotz keratometer is essentially a microscope
with a fixed working distance so that when the cornea
is in focus the apparatus is a fixed distance from it.
There are two illuminated objectives, green and red;
these are mounted on a curved track to keep them
equidistant from the cornea on either side of the
central eyepiece. To prevent any relative movement of
the images when viewing the cornea the instrument
incorporates a doubling device so that both images
move together. When the images (mires) of the two
coloured objectives are seen on the cornea in
apposition the endpoint has been reached and the
corneal curvature can be read directly from a scale on
the arms supporting the objectives. Alignment of the
horizontal bars in the mires allows the axis of
astigmatism to be increased and the corneal curvature
in the other meridian to be measured by rotating the
objectives through 90° around the axis of the telescope .
GONIOSCOPY

Gonioscopy is the visualization of the angle of the anterior chamber.

Fig. 1.39 The optics of indirect and direct gonioscopy are

illustrated. Direct gonioscopes (e.g. Barkan) provide an erect view
of the eye and are used for surgical goniotomy for buphthalmos.
Indirect gonioscopy (e.g. with a Goldmann or Zeiss lens) produces
a mirror image of the opposite angle and is used with a slit lamp
for diagnostic purposes or laser goniotomy. It can be combined
with corneal depression (indentation gonioscopy) to assess whether
the angle can be opened by the displaced aqueous. Such
indentation gonioscopy is invaluable in assessing primary angle-
closure glaucoma.

Fig. 1.40 The Goldmann indirect gonioscopy lens is a solid

perspex contact lens within which is mounted a small steep mirror.
The lens requires a coupling medium for use, such as saline or
hypromellose, as its curvature is steeper than that of the cornea.
The full circumference of the angle can be inspected by rotating
the contact lens on the surface of the eye. Lenses such as the Zeiss
4 mirror goniolens have a shallower radius of curvature and hence
do not require fluid between the lens and the cornea; however, this
makes corneal wrinkling more likely. The additional mirrors
eliminate the need to rotate the lens; such lenses will also easily
indent the cornea for indentation gonioscopy.
Left image by courtesy of Mr B Dong.

TONOMETRY

Intraocular pressure (lOP) is measured by tonometry. Most the corneal curve. Indentation tonometry (e.g. Schiotz) measures
instruments use applanation (e.g. Goldmann, air puff), which the depth of deformation rather than the area involved, and has
works on the principle that a force required to flatten a given area largely gone out of clinical use.
of corneal apex will be proportional to the lOP that maintains

Fig. 1.41 The Goldmann tonometer has an applanating surface of 3.06mm 2, at

which the effect of surface tension cancels out the rigidity of the cornea. It indents the
eye less than 0.2 mm, displaces 0.5 ml of aqueous and increases the lOP by
approximately 3 per cent which is not clinically significant. The applanation head has a
clear centre that incorporates a prismatic doubling device. Before use the corneal
epithelium is anaesthetized and stained with fluorescein to identifY the tear meniscus
around the applanating head. The prism is illuminated obliquely by the slit lamp with
the cobalt blue filter and the cornea is viewed coaxially through the applanation head
which is then gently brought to rest on the surface of the cornea. The force applanating
the cornea is increased by revolving a graduated wheel at the base of the instrument,
calibrated in millimetres of mercury.
 IMAGING THE GLOBE AND ORBIT

Fig. 1.42 This shows the endpoint at which the lOP is measured . The split
image of the tear film meniscus can be seen around the tonometer head,
outlined by the semicircular fluorescein rings with the edges just overlapping.
If the pressure on the tonometer head is too low, the resulting applanation
area is small and the split rings do not overlap; if it is too high, they overlap by
more than the thickness of the meniscus.

Fig. 1.43 The Perkins tonometer is a hand-held variant that

employs a Goldmann prism. The body rests on the patient's
forehead and the fluorescein rings are viewed through a convex
lens aligned with the prism head. It is often used for assessing lOP
in anaesthetized children or patients who cannot sit at a slit lamp.

Fig. 1.44 Noncontact applanation tonometers use a puff of air to

deform the cornea and measure the time taken to produce a set
amount of corneal flattening. This time is proportional to the lOP.
The reliability of this type of tonometer is reduced in higher
pressure ranges but it has the advantage of no contact with the eye,
thus preventing any risk of cross-infection and obviating the need
for topical anaesthesia making it ideal as a screening device in
optometric practice.

IMAGING THE GLOBE AND ORBIT

OPHTHALMOSCOPY

The direct ophthalmoscope is based on the principle that rays
emanating from the retina of an emmetropic subject will be
focused on the retina of an emmetropic observer. It consists of a
light source directed on to the patient's retina by a small angled
mirror that has a transparent area to allow light reflected from the
retina to be viewed. The image is erect and real. With an
emmetropic subject and observer, it has a magnification of xiS,
which arises from the 60D power of the patient's eye (45D
cornea+ 15D lens) behaving as a Ioupe (60/4). The field of view is
quite small at approximately 6W. A set of lenses positioned in
front of the examiner's eye allows refractive errors of either patient
or examiner to be corrected and has a range of powers from + 30
to -30D. The lenses also allow the ophthalmoscope to be focused
to view some anterior features such as media opacities. Filters can
also be rotated in the path of the returning light rays, of which the
green or ' red-free' filter is particularly useful for examining the
retinal nerve fibre layer and small vessels. Indirect
ophthalmoscopy has the advantage of a brighter light source, long
working distance, stereopsis and a wide field of view, as well as
allowing a dynamic assessment of vitreoretinal pathology. Its
disadvantages are that the image is inverted and more skill is
needed in its use. A wide variety of aspheric contact lenses is
available for retinal examination and laser treatment; these have
superseded the more traditional three-mirror fundus lens.
 Mirror

Inverted real
image of eye

+200 condensing lens

Patient' s eye

Fig. 1.45 The indirect ophthalmoscope uses a condensing lens to gather the light reflected from the subject's retina, forming a real
inverted image of the retina between the examiner and the subject. Light is derived from a source on the examiner's headpiece that is
directed into the patient's eye by an adjacent adjustable mirror. As the light source is further away from the patient's eye than with the
direct ophthalmoscope, the patient's pupils must be dilated to allow a sufficient field of illumination. The image that is formed is viewed
through an eyepiece on the examiner's headpiece; this narrows the examiner's true pupillary distance and allows binocular viewing and
stereopsis. The examiner is standing behind the patient so that the inverted image that is seen corresponds to the normal erect appearance.

Fig. 1.46 Further detail, especially at the retinal periphery, can

be seen by using an indentor to push peripheral retinal areas into
the instrument's field of view. Movement of the indentor induces
dynamic forces and helps to highlight pathology such as shallow
retinal separations or tears.
 IMAGING THE GLOBE AND ORBIT 23

Fig. 1. 47 Slit lamp stereoscopic biomicroscopy using an

aspheric lens and the same principle as indirect ophthalmoscopy
has become the technique of choice for standard clinical fundus
examination as it has the advantages of bright illumination,
stereopsis and high magnification. A wide variety of lenses are
available which have differences in magnification and field of view.

x(mm) z (mm) x(mm)

0.0 0.4 0.8 1.2 1.6 2.0 2.4 2.8 3.2 3.6 4.0 4.4 -0.4 0.0 0.4 0.8 1.2 1.6 0.0 0.4 0.8 1.2 1.6 2.0 2.4 2.8 3.2 3.6 4.0 4.4
0.0 0.0
0.4 0.4
0.8 0.8
1.2 1.2
1.6 1.6

E' 2.0 2.0 '<

.s 2.4 2.4 3
2-
2.8 2.8
3.2 3.2
3.6 3.6
4.0 4.0
4.4 4.4

-0.4 -0.8
T t) TS ~ NS Cl (j N G Nl Q Tl 14) T ()
00
1- -0.4

E'
0.4
~ 1'---.. / N

.s
N
0.8
/ "" \_ .......___..... -
0.0
3
2-
1.2 0.4

1.6 1- 0.8

0 0 0.4 0.8 1.2 1.6 2.0 2.4 2.6 2.8 3.2 3.6 4.4 0 45 90 135 180 225 270 315 360
x(mm) angle(")

Fig. 1.48 The scanning laser ophthalmoscope (SLO) uses narrow, collimated, low-power He-Ne laser light to illuminate the retinal
surface or optic nerve head. These systems have the advantage of producing real-time fundal images that can be analysed and stored
digitally. In a basic system a broad beam of low-intensity light is reflected from the fundus and detected and processed to give an image of
the illuminated area. More sophisticated systems use point-by-point raster scanning over a region of interest and, in confocal scanning laser
tomography, imaging can be conducted in different optical planes to allow subsequent three-dimensional analysis of a structure.
Introducing filters and confocal diaphragms in the path of the laser allows the nature of resulting image data to be controlled very precisely
so that unwanted reflections or scattered light can be removed to give clear pictures in conditions otherwise considered challenging for
conventional photography and to allow imaging through undilated pupils. For example, introducing an ellipsometer allows the amount of
reflected polarized light from the eye to be measured; different filters allow fluorescein, indocyanine green (ICG) or autofluoresence to be
imaged. SLOs have wide applications in clinical research and may well come into clinical practice to monitor optic disc changes in
glaucoma (see Ch. 7).
OPTICAL COHERENCE TOMOGRAPHY (OCT)
OCT obtains images by using back scattering of light in a way
analogous to ultrasound B scanning but as the wavelength oflight
is shorter the resolution is much higher. It uses a low-coherence
infrared beam that is split into a probe beam incident on the retina
and an external reference beam directed on to a mirror held at a
known distance. The incident beam is reflected by different
interfaces within the retina and retinal pigment epithelium but
penetration of deeper tissues is very limited. The two reflected
beams are then recombined and their interference is measured
producing a depth-specific interference signal with a longitudinal
resolution corresponding to depth and an amplitude corres-
ponding to the tissue reflectivity at that point. The degree of
reflectivity is displayed in false colour giving an 'anatomical'
display. Cross-sectional imaging is achieved by combining a
ScanType
ScanOate 06l23n003
Scanlength e.o
Center
TotaiVolume
ULTRASONOGRAPHY
Ultrasound is mainly used to visualize intraocular structures
through opaque media or to measure intraocular dimensions for
intraocular lens biometry or to assess tumour size. It can also be
used to visualize some orbital structures but the technique is
difficult and operator dependent. Ultrasound is reflected at
changes in tissue density. Images of the eye can be obtained in
one or two dimensions (A orB scan). A-scan images provide a
linear view along one axis and are used to measure lengths within
sequence of A-scan profiles across the retina, analogous to
ultrasound B scans. OCT has become essential in the clinical
evaluation of macular pathology such as macular holes, cystoid
oedema, pigment epithelial detachment and preretinal
membranes, and the demonstration of vitreous traction (see Ch.
12). It is less useful for investigation of subretinal pathology such
as neovascular membranes. Future developments of OCT show
great potential for measuring optic disc cupping and nerve fibre
layer thickness in glaucoma. Recently a new OCT with a
wavelength of 131 Omm has been developed for anterior segment
imaging which is likely to be of great benefit in signing the
anterior chamber for phakic intraocular lenses. This wavelength
is reflected by transparent ocular tissues such as the cornea and
lens.
PatienVScan lnfounatlon
fast Macuat ll'iekr.eS$ Map OS
Fig. 1.49 OCT data are presented as a cross-
sectional tomogram. The colour represents the degree
220 +I· 3 microns of reflectivity, where bright and dim colours
7.48 mmt
correspond to high and low reflectivity respectively.
Retinal thickness can be measured and mapped.
the eye; B-scan ultrasonography uses A scans placed together to
form a two-dimensional picture. It is a rapid, easy method of
imaging intraocular contents and also allows dynamic
examination, for example, of retinal detachment. High-frequency
probes (50 MHz) give much higher resolution but poor tissue
penetration; they are very useful for imaging anterior chamber
detail (see Ch. 7)
 IMAGING THE GLOBE AND ORBIT

A- Scan

Couplant ------,

Tra nsducer

Sound beam

Fig. 1 ~50 The scanning probe consists of an ultrasound emitter

and a transducer that detects signals echoed (reflected) from tissue
interfaces; echo amplitude is proportional to the acoustic mismatch
between adjacent tissues. In a normal eye peaks can be identified
Q) from the corneal endothelium, anterior and posterior lens surfaces,
""0
0
..c.~
::::> and the retina. The A-scan mode is used routinely to measure axial
v-
LJ.JC.. length; to do this the probe is placed directly on the patient's
E
IU anaesthetized cornea. Distance calculations are derived from the
speed of sound in each media and settings should be adjusted
Time of receiving echo
when an eye has cataract or is aphakic, pseudophakic or oil-filled.

Fig. 1.51 A B scan is a cross-sectional

image that is formed when the eye is
scanned in A mode across several planes.
The optic nerve looks dark because its
substance is homogeneous and of low
reflectance and therefore lacks tissue
interfaces from which significant
reflectivity can arise . For dynamic images,
the eye should be scanned in a horizontal
and vertical plane, with the eye stationary
and moving (up and down and from side
to side). The probe carries a marker that
orients the examiner to the plane of
imaging in the eye. Shown here are two
images of the same eye with the patient
posterior
looking left (top) and then right (bottom) .
hyaloid
tethered to There is a vitreous haemorrhage (high
optic disc signal). The detached and collapsed gel is
suspended from its basal attachments and
moves with the eye.
By courtesy of Mr E H erbert.

Fig. 1.52 High frequency probes (50 MHz) give very much
higher resolution at the expense of poor tissue penetration. It is
very useful for imaging anterior chamber detail such as angle
pathology, (see Chapter 7), ciliary body tumours or sizing AC
dimensions for anterior chamber IOLs.
By courtesy of Dr D Reinstein.
OCULAR EXAMINAIION

COMPUTED TOMOGRAPHY (CT)

CT is very useful for imaging the orbit and is the technique of

choice (in contrast to magnetic resonance imaging) if the bony
orbit, optic canal or calcification needs to be seen.

anterior ethmoid al
sinu s

medial rectus

optic nerve

sphenoid sin us

optic canal

pituitary fossa

superior rectus

optic nerve ~.I,..J..;,--J---1-+~

lateral rectus
medial rectus
inferior rectus

Fig. 1. 53 Axial and coronal CT scans of the orbit demonstrating

the orbit and its contents. Coronal views are extremely useful for
assessing intraorbital lesions as they avoid the partial volume effect
of axial scans with lesions in the superior or inferior orbit and are
easier and safer to interpret. Contrast can be given for further
enhancement of vascular lesions.

MAGNETIC RESONANCE IMAGING (MRI)

MRI is the imaging investigation of choice for orbital soft tissue
disease, optic nerve pathology and combined orbital and
intracranial pathology. Gadolinium can be given intravenously
during MRI to highlight regions of breakdown of the
blood- brain barrier. MRI does not subject the patient to ionizing
radiation. In MRI, protons (hydrogen nuclei) in tissues are
realigned when exposed to a short electromagnetic pulse but
return to their original orientation and re-emit the absorbed
energy when the pulse ends. This emission is detected, processed
and displayed as a cross-sectional image of the tissue. The
conventional MR image is derived mainly from protons in
extracellular and intracellular water and fat. Protons in proteins
or calcified tissue are tightly bound and do not contribute greatly
to the image; for this reason, bony structures and calcification
cannot be seen on MRI scans. If these changes, which are so
important in orbital disease, need to be seen CT is required. A
significant number of patients cannot tolerate MRI because of
claustrophobia.
 IMAGING THE GLOBE AND ORBIT

optic nerve

Fig. 1.54 (Left) The retrobulbar orbital fat has a high signal T 1 MRI sometimes making it difficult to visualize orbital pathology. By using
specialized sequences the fat signal can be suppressed giving much better visualization (right). This is particularly useful in identifying optic
nerve pathology.

Fig. 1.55 T,-weighted scans

have a low CSF signal and
provide excellent anatomical
detail. With T 2 weighting the
anatomical detail is less clear
but pathological lesions are
frequently demonstrated
more easily. This patient has
wh ite matter lesions
white matter lesions in the
left cerebral hemisphere
white matter f---1-1:-'r'---
compatible with
bone demyelination in a young
scalp fat~----"~'--­ adult or small vessel vascular
-..:::::::-::::::::-/
disease in the elderly.
ocULAR EXAMINATION

marrow in sku ll
meningioma enhances
high signal from CSF uniformly with gadoli nium

T2 -wei ghted scan

T1 -we ighted scan

Fig. 1.56 Intravenous gadolinium shows breakdown of the blood- brain barrier in a way analogous to CT scanning with IV contrast
enhancement and is particularly useful in demonstrating pathology and the extent of a lesion and surrounding oedema. This patient has a
cavernous sinus meningioma. The lesion shows typical uniform enhancement with gadolinium and its anatomical extent can be seen much
more easily. It surrounds the ipsilateral carotid artery and spreads through the pituitary fossa to the contralateral sinus.

anterior
cereb ral artery
posterior 1
communicating artery internal
'of--- ---"":-1 ca rotid artery

middle
cerebral artery

Fig. 1.57 Magnetic resonance angiography (MRA) has now largely superseded other forms of cerebral angiography as a diagnostic
technique as it is noninvasive and therefore avoids the risk of traditional angiography. This image shows the vascular anatomy of the circle
of Willis.
With permission from Yanoff et al (eds) Ophthalomology © 2003 Elsevier Inc.
 ELECTRICAL TESTS OF RETINAL FUNCTION

ELECTRICAL TESTS OF RETINAL FUNCTION

Electrophysiological examination provides objective data on
visual pathway function. The main tests are electro-oculography
(EOG) which examines the function of the retinal pigment
epithelium and the interaction between it and the
photoreceptors; electroretinography (ERG) which arises in the
photoreceptors and inner nuclear layers of the retina and is the
mass response of the retina to a full-field luminance stimulus;
Pi gment } EOG
epithelium
Photo receptors
pattern electroretinography (PERG) which allows assessment of
both macular and retinal ganglion cell function; and
measurement of the visual evoked cortical potential (VEP) which
assesses the optic nerve and intracranial visual pathways.
Electrodiagnostic tests are useful in localizing and diagnosing
both inherited and acquired retinal and visual pathway disorders
and, where appropriate, in monitoring the efficacy of treatment.
They can also assess visual function in eyes with opaque media
and retinal function from drug toxicity. In addition, they are
particularly valuable for diagnosing nonorganic visual loss. Dark
adaptation and other psychophysical tests may be used in
conjunction with electrophysiological tests. The International
Society for Clinical Electrophysiology of Vision (ISCEV) has
published minimum standards for electrodiagnostic testing and
standardized recording and has greatly improved the
communication of electrophysiological data.

Horizontal cells ERG

Outer synaptic layer

Bipolar cells

Fig. 1.58 The regions of the retina responsible for generating the
various electrical potentials. The EOG is generated by the retinal
Amacrine cells pigment epithelium-photoreceptor complex and photoreceptors.
Inner syna ptic layer The ERG is a complex potential, reflecting photoreceptor and
inner nuclear layer function . The PERG is partially generated in
Pattern the ganglion cells (N95 component), providing objective data on
Ganglion cel ls

Reti na l nerve
J ERG
ganglion cell function and partially in the more distal retina (some
of the PSO component). However, much of the PSO component is
fibre layer driven by the macular photoreceptors and so provides an objective
VEP index of macular function. The VEP provides objective assessment
Optic nerve
of the retrobulbar and intracranial pathways.

DARK ADAPTATION

This measures the increase in retinal sensitivity with time in the
dark-adapting eye and is due to regeneration of rhodopsin. The
visual threshold to a flash of light is plotted against time after
bleaching to a standard bright light. Normally, after
approximately 7 min of adaptation, the sensitivity of the rods
overtakes that of the cones. This is known as the cone-rod break.
After 25-30 min rhodopsin has fully regenerated and retinal
sensitivity has reached its peak. Defects in rod metabolism, such
as retinitis pigmentosa, will produce abnormally high thresholds
at this time . In practice the test is time consuming and difficult
to perform and the equivalent information can usually be
obtained more easily by EOG and ERG.

II ~ =·=·=·=·=·=-=·=·=·=·=•='•~
7 10 20 30
so

40
;;;;:,
Fig. 1.59 Dark adaptation curve. Threshold light intensity is
plotted against time following bleaching by a bright flash and
shows that the retina becomes more sensitive as rhodopsia is
regenerated. The three lines indicate different retinal thresholds at
0, 2.5 and 5° from the fovea and show that dark adaptation
increases eccentrically from the fovea as the population of rods
Minutes in dark increases. The cone-rod threshold at 7 min is shown.
ELECTRO-OCULOGRAPHY (EOG)

There is a standing potential within the eye of approximately in the retinal pigment epithelium. The cornea is positive m
6mV between the cornea and retina that arises from interactions relation to the retina.

...__
Left gaze Right gaze
Fig. 1.60 This potential can be measured by surface electrodes
placed on the medial and lateral canthi. The patient is asked to
Right gaze make horizontal eye movements between two fixation lights that
alternate from right to left, 15° either side of centre, enabling
constant 30° excursions to be made . Movement of the cornea to or
away from the electrodes thus induces an electrical potential which
is amplified and recorded. During a period of scotopic adaptation,
soov I
I the potential falls to a minimum - the dark trough - after
I
I
I
I
approximately 12 min of dark adaptation. The potential reaches a
I
I
I
maximum after approximately 8-10 min of photopic adaptation,
I
I reflecting progressive depolarization of the basal membrane of the
Left gaze l_ ___ ~_s_e_c!___ _ retinal pigment epithelium.

Fig. 1.61 Clinically the test is performed with dilated pupils using a Ganzfeld bowl, which produces uniform retinal illumination during
the photopic phase. The patient sits with their chin on the chin rest. During EOG recording only the central fixation light is illuminated.
On either side (15 ° from centre) are the two LEDs that the patient fixates alternately during the test. Below the central fixation light there
is a small infrared camera for monitoring the patient. The potential is measured during scotopic adaptation for 20 min, during which time
the dark trough occurs. The illumination is then increased to photopic levels and recordings are continued for a further 15 min or until the
light peak has been reached. The ratio of light peak to the dark trough should exceed 175 per cent in normals. A reduced EOG light rise
indicates dysfunction at the level of the retinal pigment epithelium-photoreceptor complex. Accurate assessment of the EOG requires the
patient to be able to make accurate and replicable horizontal eye movements and although readings are not affected by opacities in the
ocular media dense cataracts prevent compliance as the patient cannot see the fixation lights.
By courtesy Mr C R Hogg.
 ELECTRICAL TESTS OF RETINAL FUNCTION 31

Normal EOG EOG with

Retinitis Pigmentosa
.~ .~
c c
::l ::l
Q)
Dark Light rise QJ
Dark No light rise
"0
::l
200% "0
::l
.~ .~
c. 3 3
E .'"''·~· =·~·· ·; ·. D..
E
••
2 ro 2
"'
Q)
>
·,.:; ••• ·.~..!.~.. .. . ..! . ~.~-~
QJ
>
·.;::;
······················
"'
Q)
~
Q)
cr: cr:
Time (mins) Time (mins)

+"
c Fig. 1.62 Typical tracings of a normal patient compared with
c Q)

il
0 Q)
:>,
Q)
llllllll llllllll 111 111 11 11111 11 11111 11
those from a patient with retinitis pigmentosa. There is neither an
EOG dark trough nor a light rise in the patient with retinitis
pigmentosa. The test is particularly useful in the diagnosis of Best's
vitelliform macular dystrophy (see Ch. 16).

ELECTRORETINOGRAPHY

The ERG is the mass electrical response of the retina to a response (the rod-specific B-wave) is generated in the inner
luminance stimulus, usually a brief light flash. Stimulation is nuclear layer and thus does not allow distinction between
delivered by a Ganzfeld bowl which provides uniform whole-field photoreceptor dysfunction and postphototransduction dys-
illumination as well as a diffuse background light for photopic function. This distinction is better seen in the bright-flash ERG
adaptation. As the ERG is a mass response it remains normal response where significant a-wave reduction indicates
when retinal dysfunction is confined to small areas; an eye with photoreceptor dysfunction (see Fig. 1.65), such as occurs in
disease confined to the macula also has a normal ERG despite genetically determined photoreceptor degenerations. If the site of
the high photoreceptor density of the macula. By varying the dysfunction is postphototransduction there may be a normal
recording conditions selective defects can be demonstrated in the a-wave with selective B-wave reduction (the so-called negative or
rod or cone systems and some information can be obtained electronegative waveform; see Fig. 1.65). Among the diseases
about the location of the defect within the phototransduction that lead to a 'negative' ERG are X-linked congenital stationary
pathway. night blindness, X-linked juvenile retinoschisis, central retinal
A standardized bright flash is given. The response to this flash artery occlusion and quinine toxicity.
under scotopic conditions with a fully dilated pupil, is the Cone-specific ERGs are recorded when the retina is
maximal or mixed response (see Fig. 1.64). This response, stimulated under conditions of photopic adaptation. This is done
perhaps regarded by many as the 'typical' ERG is dominated by by increasing the background illumination to suppress the rods
rod-driven activity. The initial negative component is known as and using both single-flash and 30-Hz flicker stimulation. At
the a-wave, approximately the first 10 ms of which reflects 30Hz the poor temporal resolution of the rod system, in addition
photoreceptor hyperpolarization; the A-wave slope reflects the to the presence of the rod-suppressing background, enables a
kinetics of phototransduction. The larger positive B-wave which cone-specific waveform to be recorded (see Fig. 1.64)
follows the A-wave is generated after phototransduction in illumination. It is a more sensitive measure of cone dysfunction
relation to 'ON' bipolar cell depolarization. The oscillatory
but is generated at an inner retinal level. In contrast, the single-
potentials, the small wavelets seen on the B-wave, probably relate
flash cone response gives better localization within the retina.
to activity in the amacrine cells. When the standard flash is
Although there is a contribution of the hyperpolarizing (OFF)
reduced by 2.5 log units a rod-specific response is obtained
bipolar cells to shaping the photopic a-wave, the cone
consisting purely of the inner nuclear derived B-wave; at these
low luminance levels, even under scotopic adaptation, there is photoreceptors probably also contribute to the generation of this
insufficient photoactivation to record an A-wave (see Fig 1.64). component. The cone b-wave reflects postphototransduction
The ISCEV standard rod-specific response is generally the activity. There is no significant retinal ganglion cell contribution
most sensitive detector of rod system dysfunction. However, this to the clinical (flash) ERG.
OcULAR EXAMINATION

Fig. 1.63 The main recording electrode for the ERG is corneal,
and is often a contact lens electrode, but gold foil and loop
electrodes in the fornix are also acceptable and in common use.
The reference electrodes should be positioned at the outer canthi.
Corneal electrodes that do not alter the optics of the eye can be
used for both full-field and pattern ERG recording. The gold-foil
electrode is a thin layer of gold leaf with a mylar base placed over
the lower eyelid so that it is in contact with the lower limbus of the
cornea; it is important that it does not touch the skin of the lower
eyelid. Surface-active electrodes can be used in unsedated infants
to give .adequate but limited recordings; ERGs can also be
recorded under general anaesthesia.

PATTERN ELECTRORETINOGRAPHY

The pattern electroretinogram (PERG) must be recorded using
electrodes that do not alter the optics of the eye; contact lens
electrodes are thus unsuitable. The patient views a reversing
chequerboard or grating, similar to that used for the VEP, rather
than a flash of light. The signal is of very low amplitude
compared with the full-field ERG; computer averaging is
essential and attention to detail is necessary to obtain satisfactory
recordings. The normal PERG to a high-contrast chequerboard
pattern consists of two main components: a prominent positive
component the PSO, followed by a larger negative component,
the N95 .
Recent work suggests that all of the N95 component and
some but not all ofPSO, relates to ganglion cell function. The PSO
component is almost invariably affected in macular disease and
its amplitude serves as an objective assessment of macular
function. With optic nerve disease the N95 is selectively affected
as a result of retrograde axonal degeneration of the ganglion cells.
Visual loss from maculopathy or optic neuropathy can therefore
be distinguished.

Normal electrophysiological recordings

Scotopic rod Maximal

400V 600V B-wave

B-wave
soov
300V 400V
"'
\.9
300V
c:r::
U.J
200V
200V
100V
100V
ov ov A-wave Fig. 1.64 Typical normal electrodiagnostic waveforms. A bright
OS 100mS OS 100mS white light (of standardized intensity) in a dark-adapted eye gives a
mixed rod-cone response with a prominent A-wave although this
30Hz fl icker Photopic response is dominated by rod function. The first 10-12 ms of the
150V Peak B-wave A-wave reflects the kinetics of phototransduction. Amplitude and
150V
implicit time of the A- and B-waves are measured. Note the
100V 100V presence of the amacrine cell-related oscillatory potentials on the
"'
\.9
c:r:: B-wave which can be enhanced by selective filtering. A dim flash in
U.J
sov sov a fully dark-adapted eye gives a scotopic rod-specific response
ov ov consisting of a positive B-wave with no recordable A-wave .
Amplitude and implicit time (the time to peak) of the b-wave peak
OS SOmS OS SOmS are measured. Cone function is assessed under photopic conditions
using a rod-suppressing background with a 30-Hz white light,
4V 10V P100 which gives a cone-derived flicker response, or single-flash
PSO
2V sv stimulation. The flicker response and A- and B-wave amplitude and
\.9 a.. implicit times are measured for the photopic single-flash response.
c:r::
U.J
ov LJ.J
> ov Measurement of the PERG focuses on the amplitude and timing of
c.. a..
-2V the PSO component and the amplitude of the N95 component.
- SV
-4V N95 Both components are measured 'peak-to-peak'. Pattern visual
- 10V N135
evoked potential measurement concentrates on the implicit time
OS SOmS 1OOmS OS 100mS 200mS (often referred to as latency) and amplitude of the P 100 peak.
 ELECTRICAL TESTS OF RETINAL FUNCTION

l j 150V
(M] 150V
Photo pic PE RG

QJ
Scotopic rod Maximal 30Hz fl icker

No rmal
40 V[G 40 V
200V
200V
100V
50V
100V
4V~
2V
ov
-2V
50V
ov ov ov ov -4V

bJ 150VD 150V CJ
OS l OOmS OS lOOmS OS 50mS OS 50m S OS l OOmS

Retinitis Pigmentosa
(macula involved)
40 VD 40 V
200V

ov
200V

ov
100V
50V
ov
-
100V
50V
ov
4V~
2V
ov
-2V
-4V

40 VD 40 Vbd 150VbbJ 150VD 4VB

OS l OOmS OS lOOmS OS 50mS OS 50m S OS lOOmS

2V
100V 100V
Cone-rod dystrophy 200V 200V ov
50V 50V -2V
ov ov ov ov -4V

40 V
[;d 150V
[W 4VB
OS lOOmS OS lOOmS OS 50mS OS 50mS OS lOOmS

400V~ 100V 150V~

100V
2V
ov
Macu lar dystrophy 200V 200V 50V 50V -2V
ov ov ov ov -4V

40 VD 40 V
g 4VB
OS lOOmS OS lOOmS OS 50mS OS 50mS OS l OOmS

150V~
100V
150V~
100V 2V
X-l inked CSNB 200V 200V ov
50V 50V -2V
ov ov ov ov -4V
OS lOOmS OS lOOmS OS 50mS OS 50mS OS lOOmS

Fig. 1.65 Examples of ERGs to show the ability of the ERG both to separate rod and cone system function and to ascertain the degree
of dysfunction . Typical normal findings are shown for comparison. In the patient with retinitis pigmentosa, the rod-specific ERG B-wave is
profoundly subnormal. The marked reduction in the maximal A-wave response confirms that this is related to photoreceptor dysfunction.
Cone single-flash and flicker ERGs both show amplitude and implicit time abnormalities but the changes are less severe than those in the
rod system . Thus, the patient has a rod- cone dystrophy. The subnormal PERG confirms macular involvement.
The rod system in the second patient is affected in a similar manner to that of the patient with retinitis pigmentosa but the cone system
shows only residual activity. This patient therefore has a cone-rod pattern of dysfunction. The patient with a macular dystrophy has normal
full-field ERGs with only the PERG being abnormal. The patient with X-linked congenital stationary night blindness has no detectable
rod-specific ERG in keeping with severe dysfunction of the rod system. However, the maximal response is profoundly electronegative; the
normal a-wave indicates normal photoreceptor function but the reduced b-wave indicates the site of dysfunction to be
postphototransduction.

VISUAL EVOKED POTENTIAL

The visual evoked potential (VEP) is the electrical response of
the visual cortex to visual stimulation and is recorded using
posteriorly situated scalp electrodes. It is extracted from the
spontaneous higher-voltage background activity of the brain, the
electroencephalogram, by using repetitive stimulation and
computerized signal averaging. The VEP, like the PERG, varies
with stimulus and recording parameters. The normal-pattern
VEP response to a slowly (approximately 2 cycles per second)
reversing black and white chequerboard in constant luminance
contains a prominent positive peak at about 100 ms; this is
known as PlOO (see Fig. 1.64), and its amplitude and latency are
measured. This pattern-reversal VEP is most commonly used in
routine clinical practice.
VEPs can also be stimulated by pattern appearance
(onset/offset), where a uniform grey background is replaced by a
chequerboard of identical mean luminance or a diffuse flash
stimulus. The flash VEP is useful when assessing uncooperative
or unconscious patients and patients with VEPs of irregular
pattern. It is usually less sensitive to disease than the pattern VEP
and shows much greater interindividual variability. Within an
individual, however, there is minimal interocular or inter-
hemispheric asymmetry.
VEPs are particularly useful for detecting and diagnosing
optic nerve disease. Optic nerve demyelination profoundly delays
the VEP and this is almost invariable following a clinical episode
of optic neuritis and may also be seen in subclinical disease.
Ischaemic optic neuropathy tends to affect amplitude rather than
latency. Although optic nerve disease often results in VEP delay,
VEP delays also commonly occur with macular dysfunction so
that the PERG may be needed to distinguish accurately between
14 OCULAR EXAMINATION

optic nerve and macular disease. The VEP can also be useful in
the assessment of chiasma! function by comparing responses
from the nasal and temporal hemifields. The VEP to both flash
(in younger children) and pattern appearance (in older patients)
is the investigation of choice in identifying the abnormal
intracranial misrouting of albinism. VEPs also have a valuable
role in the diagnosis of nonorganic visual loss, where they can
objectively demonstrate normal function in the presence of
symptoms that suggest otherwise.

Fig. 1.66 The VEP is recorded by placing electrodes on the scalp

(electrodes placed on the right occiput record signals from the left
occipital cortex). Repeated responses to the reversing
chequerboard stimulus are recorded and averaged. It is important
to ensure the patient is fixating on the pattern because loss of
fixation can cause artefacts; this is especially important in patients
suspected of having nonorganic visual loss.

PVEP PERG
P100

6/SRE ~~ ~
0 P100 PSO _j20V
Fig. 1.67 Pattern visual evoked potentials (PVEPs) and PERG in
a patient with recovered retrobulbar neuritis. Despite clinical
recovery to normal visual acuity the PVEP P100 component is

6/s LE ~ ~~sov 100mS

SOmS
delayed to 135 ms in the affected right eye. Note the symmetical
PERG PSO component in both eyes but selective reduction of the
N95 component in the right-eye PERG which is due to
degeneration of the retinal ganglion cells following the episode of
optic nerve demyelination.

PVEP PERG

RE ~~ PSO

0 P100
_j4V
80mS
Fig. 1.68 PVEP and PERG in a patient with left inflammatory
maculopathy. The P 100 component of the VEP is delayed and

LE:~
broadened in the affected left eye and the PERG PSO component
is reduced and delayed. Compare this PERG abnormality with the
N95 abnormality consequent upon retrograde degeneration to the
retinal ganglion cells in the patient with retrobulbar neuritis in
Fig. 1.67.
The Eyelids
Eric Barnes, Richard Collin

Normal Anatomy
Congenital Eyelid Abnormalities
Eyelid Malposition
Eyelid Tumours
Eyelid Trauma
6 THE EYELIDS

NORMAL ANATOMY

The eyelids protect and maintain the cornea. The structure of both the upper and lower eyelids is similar; each lid consists of two layers
or lamellae. The anterior lamella consists of skin and orbicularis muscle, and the posterior lamella of tarsal plate and conjunctiva. The
orbital septum extends from the orbital rim to the tarsal plate and separates the preseptal orbicularis muscle from the pre-aponeurotic
fat pad. The lid retractors lie deep to this pre-aponeurotic fat pad. The upper lid retractors consist of the levator palpebrae superioris
muscle, its aponeurosis and the superior tarsal muscle (Muller's muscle). The lower lid retractors arise from the sheath of the inferior
rectus muscle and are similarly composed of an aponeurosis and smooth muscle (the inferior tarsal muscle).

Fig. 2.1 Diagrammatic view of the structures of the

Frontalis normal eyelid. The orbicularis muscle can be divided into
Cross-section
muscle of levator the pretarsal, the preseptal and orbital parts although
aponeurosis these are not separate anatomically. The pretarsal and
Pre-septal
muscle
preseptal parts together form the palpebral section of the
Superior orbicularis muscle which is responsible for blinking and
Medial tarsal plate facilitates the drainage of tears (see Ch. 20) and the
cantha l Inferior orbital part is responsible for forced lid closure. The grey
tendon tarsal plate line is where orbicularis oculi meets the lid margin. This
Pre-tarsal visible line lies anterior to the meibomian gland orifices
Orbital
muscle and posterior to the eyelashes. It is the plane at which the
anterior and posterior lamella can be separated during
Orbital part
of orbicularis
surgery. Removal of the orbicularis muscle exposes the
muscle underlying tarsal plates and orbital septum. The levator
aponeurosis is the tendon of the levator muscle which
inserts between the orbicularis muscle bundles and is
responsible for the eyelid skin crease.

Levator palpebrae - - - - -+-----1---------

superiori s muscle

Superior suspensory ------+--f---f~~::;:;:::;::;=;~

ligament of the globe
Fig. 2.2 The pre-aponeurotic fat pad lies behind the
Lacri ma I gland - -- ---1----,'--./f-K_::::::::;z:=:::=::- orbital septum. If it is elevated, the levator palpebrae
superioris muscle with its aponeurosis is seen. Whitnall's
Levator aponeurosis - -- - --\:--./\
ligament (the superior suspensory ligament of the globe)
Tarsal plates - - -- - - - \ -+-_L__"""""'-'<..
--...,;,..u,/L/" is a thickening in the aponeurosis that helps to support
Inferior aponeurosis - -- - ---+- -- --" the aponeurosis and the upper lid retractors. It runs from
Med ial cantha l tendon - -- - -- + - -- --7---" the periosteum of the lacrimal gland fossa to the trochlea
Lacrimal sac - - -- ----'"<-+---" of the superior oblique muscle. The inferior aponeurosis
is the forward extension of the connective tissue from
Lockwood's ligament (the inferior suspensory ligament of
the globe) and is continuous posteriorly with the sheath
around the inferior rectus muscle (see Fig. 2.5).
 NORMAL ANATOMY

Preaponeurotic fat pad --------h~~

Levator pa lpebrae
superioris muscle - -- - - -- +1--ZJIH--=-,

Superior suspensory
ligament of the globe - - - -- -fi'-----,7-t......,_,c___ -:::::.--...:...:..:__--·c.c
Aponeurosis ------,~i"-"'~0-'

Superior tarsal
(Muller's) musc Ie ---f-1'--7<7?777f:>P'.
Fig. 2.3 The upper lid structures can be compared in
diagrammatic and histological vertical sections. The levator
palpebrae superioris muscle inserts into the anterior lamella and
the posterior lamella (Muller's muscle) , both of which are
responsible for lifting the eyelid. The connective tissue between the
levator muscle and the superior rectus muscle (the common
sheath) extends forward to support the upper conjunctival fornix
(superior suspensory ligament of the fornix) .

levator muscle
Muller's muscle
superior
rectus muscle

Fig. 2.4 Histological section of the upper lid corresponding to the cross-sectional diagram of Fig. 2.3.

Fig. 2.5 Sections of the lower lid show the arrangement of the
lower lid retractors. A condensation of fascia around the inferior
oblique muscle forms the inferior suspensory ligament of the globe
(Lockwood's ligament). This is analogous to Whitnall's ligament in
the upper eyelid. It is attached medially and laterally in the region
of the canthal tendons and can support the globe if the orbital
floor is removed. The inferior aponeurosis extends forwards from
Inferior suspensory Lockwood's ligament with the inferior tarsal muscle (analogous to
igament of the globe --H---;.o"--Je-----=~-r-- Muller's muscle in the upper lid). These are the lower lid retractors
lnferior oblique ---++-~~+---+-___/ which are responsible for depressing the lower eyelid on downgaze
muscle due to their connection with the inferior rectus muscle. A forward
extension of the connective tissue associated with the lower lid
retractors forms the inferior suspensory ligament of the fornix and
anterior part ofTenon's capsule.
THE EYELIDS

inferior tarsal
muscle anterior part
of Tenon's capsule

inferior rectus
inferi or obligue " ,~­ muscle
muscle

Fig. 2.6 Histological section of the lower lid corresponding to the cross-sectional diagram of Fig. 2.5.

CONGENITAL EYELID ABNORMALITIES

Fig. 2.7 Congenital lid colobomas are the result of a failure of

normal development of the eyelid and closure of the facial clefts.
Urgent repair is required only if the defect is so severe that the
cornea is likely to suffer permanent damage from exposure .

Fig. 2.8 Epicanthic folds are abnormal folds of skin at the medial
canthus. They are common in childhood, especially in children of
oriental origin, but they may also be acquired as a result of tissue
loss from trauma . Congenital epicanthic folds frequently give an
appearance of pseudostrabismus (see Ch. 18) . They usually
become less obvious with age but, if they persist, both congenital
and acquired folds can be treated by a variety of plastic surgery
procedures.

Fig. 2.9 Blepharophimosis. These patients have epicanthus

inversus, telecanthus and ptosis as well as blepharophimosis. Lower
lid ectropion may also be present. Levator function may be poor;
some patients have a dominant family history.
 EYELID MALPOSITION 39

EYELID MALPOSITION

All forms of eyelid malposition may be congenital or acquired.

ENTROPION

Entropion is a rotation of the eyelid margin from its normal position towards the globe. The degree of lid laxity needs to be assessed
to plan surgical correction.

Fig. 2.10 Horizontal lower lid laxity is assessed by grasping the lower lid skin and applying gentle traction away from the globe. (a) The
extent to which the lid can be lifted off the globe is measured in millimetres; more than 6 mm is considered abnormal. (b) Laxity of the medial
canthal tendon is assessed by gently pulling the lid laterally. The position of the punctum in relation to the limbus or pupil in primary gaze is
then recorded. Lack of a lower lid skin crease in downgaze implies disinsertion of the inferior retractors.

Fig. 2.11 Congenital lower lid entropion is caused by

hypertrophy of the skin and underlying orbicularis muscle. A mild
degree of this hypertrophy is common in young children
( epiblepharon) and, rarely, the eyelid margin itself inverts
(congenital entropion). Should this fail to improve with age and
cause irritation of the eye, it is corrected by the excision of the
hypertrophic skin and underlying orbicularis muscle.
40 THE EYELIDS
Fig. 2.12 Involutional entropion is a common condition caused
by ageing changes affecting the orbicularis muscle, the lower lid
retractors, the tarsal plate, the medial and lateral canthal tendons
and the orbital fat. A variety of operations has been described to
correct various combinations of these defects. These include
sutures or incisions designed to prevent the upward movement of
the preseptal muscle, tightening the lower lid retractors, eversion of
the upper border of the tarsal plate and horizontal lid and canthal
tendon shortening procedures.
ECTROPION
Ectropion is a rotation of the eyelid margin from its normal
position away from the globe. Eversion of the lid margin results
from a combination of factors such as inferior retractor
disinsertion and laxity of the horizontal lower lid or of the medial
or lateral canthal tendons. These are usually seen as an ageing
Fig. 2.14 Congenital ectropion in neonates and very young
children may be caused by crying and spasm of the orbicularis
muscle . This does not usually require ·any treatment. If there is a
shortage of skin, as in the case illustrated here, skin replacement is
necessary with a graft or flap.
Fig. 2.13 Cicatricial changes can affect the posterior lamella of
either the upper or lower lid and lead to entropion. This patient
has scarring and shrinkage of the tarsal plate and conjunctiva.
Common causes include trauma, acid and alkali burns, trachoma
and other chronic conjunctival inflammations such as chronic
staphylococcal lid disease, ocular pemphigoid or Stevens-Johnson
syndrome. It may be possible to correct a cicatricial entropion with
an everting procedure and rotation of the tarsal plate but if there is
a marked degree of lid retraction a posterior lamellar graft will be
required to lengthen the posterior lamella.
phenomena but may be related to the floppy eyelid syndrome.
Scarring of the anterior lamella of the lid (cicatricial), orbicularis
muscle weakness (paralytic) or lumps (mechanical) are the other
categories of acquired ectropion.
Fig. 2.15 Involutional lower lid ectropion is caused by a
generalized laxity of all the lid tissues aggravated by gravity. Various
operations have been described to correct the condition; most of
these involve a horizontal shortening procedure of one or both
lamellae or tightening of the canthal tendons with or without the
removal of excess skin and orbital fat. Chronic exposure may cause
conjunctival keratinization, puncta! stenosis and chronic infection.

Fig. 2.16 Cicatricial lower lid ectropion may be caused by any
condition that leads to a shortage of skin. This patient fell off his
bicycle and lost skin; the resultant scarring caused a cicatricial
ectropion. Surgical correction involves excision of the scar tissue,
and replacement skin grafting. The lid must be shortened at the
same operation if it has been stretched excessively by the scarring.
Fig. 2.18 Any form of lump on the lower lid can lead to a
mechanical ectropion. The patient illustrated here has a localized
neurofibroma of the lower lid. Treatment involves the excision of
the tumour and correction of any induced horizontal laxity of the
lid.
EYELID MALPOSITION 4'
Fig. 2.17 Paralytic ectropion is caused by weakness of the
orbicularis muscle (seventh nerve palsy) and subsequent lid laxity.
Corneal exposure may be a problem, particularly if there is
reduced trigeminal sensation (e.g. with a cerebellar pontine angle
tumour such as acoustic neuroma). Bell's phenomenon protects
the cornea on forced eyelid closure, but is not always present. The
cornea can be protected by transient ptosis induced by botulinum
toxin if recovery of the seventh nerve palsy is expected. Medial
canthalplasty and a lateral canthal sling may help, and a variety of
other procedures such as fascia lata slings may be useful. The loss
of brow wrinkling indicates this patient has a lower motor neurone
seventh nerve palsy.
Fig. 2.19 The characteristics of the floppy eyelid syndrome are
easy evertion of the upper lid and a chronic papillary conjunctivitis
(which is caused by the mechanical abrasion of the upper tarsal
conjunctiva on the lower lid lashes). It is associated with obesity
and sleep apnoea and is a risk factor for cardiovascular and
cerebrovascular disease. Patients need investigation for these
underlying conditions.
PTOSIS
Blepharoptosis (ptosis) is a reduction in the vertical palpebral
aperture due to descent of the upper lid as a result of pathology
involving the eyelid retractors. A useful classification of ptosis can
be made by considering pseudoptosis and congenital or acquired
ptosis (Table 2.1). Pseudoptosis is associated with such problems
as orbital volume deficiency, excess lid skin or hypotropia.
Congenital ptosis is usually due to a dysgenesis of the levator
palpebrae muscle which may be either unilateral or bilateral and
may also affect the superior rectus, causing poor elevation of the
eye. Acquired causes include myopathic, neurogenic, mechanical
or aponeurotic defects. A careful history and examination is
required for each patient paying special attention to such features
as duration, progression or variability, associated symptoms such
as diplopia and systemic muscle weakness and factors such as
birth trauma, head or orbital injury and contact lens wear.
Table 2.1 Table of causes of ptosis
Ptosis subtype
Congenital Levator dysgenesis
Non-dysgenetic
Acquired Aponeurotic dehiscence
Myopat hic
Neuromuscular junction
Neurogenic
Mechanical
Examination should assess the degree of ptosis. In the
primary position of gaze the upper lid usually covers the corneal
limbus by 1-2 mm. The lower lid position should not be ignored;
it normally reaches the corneal limbus. The marginal lid to
corneal light reflex distance (margin-reflex distance) and width
of the palpebral apertures should be recorded, and irregularities
of lid curvature noted. Skin show is the distance between the
eyelid margin and the upper-lid skinfold in primary gaze. The
skin crease is the line of insertion of the levator aponeurosis into
the skin and is measured in millimetres as the distance between
the eyelid margin and the skin crease in downgaze. Finally, Bell's
phenomenon should be elicited and a search m ade for signs of
systemic or neurological disease.
Aetiology
Simple levator dysgenesis
Combined levator and superior rectus dysgenesis
Congen ita l aponeurotic defect third nerve palsy, Horner's syndrome,
Marcus Gunn syndrome, etc.
Involutional
Contact lens wear
Chron ic prog ressive externa l ophthalmoplegia
Ocu lopharyngeal dystrophy
Myotonic dystrop hy
Myasthenia gravis
Third nerve palsy
Horner's syndrome
Any upper lid mass or cause of upper lid inflammation or scarring
Direct muscle t rauma
Fig. 2.20 Congenital ptosis. If the visual axis is not occluded by
the eyelid it is reasonable to delay correction of a congenital ptosis
until the child is old enough for a more accurate assessment when
definitive surgery may be performed, usually around the age of 4
years. Congenital ptosis is also frequently associated with refractive
errors that need correcting to prevent anisometropic amblyopia.
Fig. 2.21 Lid position on downgaze should be examined.
Congenital dystrophy of the levator produces hang-up in downgaze
because the levator does not relax properly and tethers the lid. This
is accentuated by asking the patient to adopt a chin-up head
posture. The skin crease position of both upper lids should be
noted.
 EYELID MALPOSITION

Fig. 2.22 Aponeurotic disinsertion is one of the commonest causes of ptosis. It is characterized by an elevated skin crease and increased
ptosis on downgaze in the presence of normal levator function. This is frequently compensated for by overaction of the frontalis. This
patient shows bilateral ptosis, worse on the right than the left, with high skin creases and bilateral frontalis overaction. The right upper lid is
more ptotic on downgaze . Caution is required as identical changes can be seen in myasthenia gravis.

Fig. 2.24 Ocular myopathy usually presents as a bilateral

Fig. 2.23 The type of operation is governed primarily by the
degree of remaining levator function which is assessed by
measurement of the excursion of the upper lid from full downgaze
to full upgaze . The frontalis muscle is prevented from acting by
pressure over the brow. If levator function is 4 mm or better, the
muscle can be shortened. Poorer levator function requires an
alternative method of elevation such as a brow suspension.
progressive and symmetrical ptosis with a poor range of ocular
movement, slow saccades on rapid gaze and weakness of the
orbicularis. Most cases are due to a mitochrondrial myopathy but
myasthenia gravis needs to be excluded in all cases. Ocular
myopathy may be associated with systemic features such as
generalized muscle weakness, swallowing difficulty and heart block.
Surgical correction must be approached with caution as these
patients usually have a poor Bell's phenomenon and corneal
exposure may result. Surgery is feasible only under local
anaesthesia and the patient must be prepared to have the eyelid
level adjusted at a later stage if the myopathy deteriorates. Ptosis
props may be useful. Note the bilateral frontalis overaction in this
patient and the loss of upper facial expression.
 pigment
clumping

Fig. 2.25 This fundus photograph shows a mild peripheral pigmentary retinopathy in a patient with an ocular mitochondrial myopathy.
The changes are often subtle and are not as florid as in retinitis pigmentosa. The ERG may be abnormal.

ragged red fibres

variable
fibre diameter

Fig. 2.26 Mitochondrial abnormalities are best demonstrated in a skeletal muscle biopsy by the presence of 'ragged red fibres' as seen in
Gomori trichome stained sections.
By courtesy of Dr PH McKee.

Fig. 2.27 With a third nerve palsy, the eye deviates downwards and outwards as a result of the remaining action of the lateral rectus and
superior oblique muscles. Depending on the cause of the palsy, the pupil may or may not be involved. Signs of aberrant regeneration
should be looked for in all patients (see Ch. 19). This elderly woman has a complete ptosis. On elevating the lid it can be seen that she
cannot adduct the eye; notice, too, that the pupil is not enlarged which suggests that the palsy is likely to be due to microvascular
ischaemia, a common cause in the elderly.

EYELID RETRACTION
The height of the upper lid in relation to the limbus is dependent
on mechanical forces such as the globe to orbital volume, the
neural activity of the eyelid retractors and pathology of the ocular
muscles or levator. Eyelid retraction must be differentiated from
conditions such as proptosis and high myopia, as well as from
contralateral ptosis. Scleral show on downgaze confirms the
presence of primary lid retraction; if lid retraction is secondary to
EYELID MALPOSITION
Fig. 2.28 The sympathetic supply to the superior tarsal muscle
(Muller's muscle) is disrupted in Horner's syndrome (see Ch. 19);
this results in a ptosis ofthe upper lid of 1- 2 mm. Miosis and
'inverse ptosis' of the lower lid may also be seen. In this case,
hypopigmentation of the affected right iris suggests a congenital or
extremely long-standing aetiology. In acute lesions hyperaemia of
the conjunctiva and loss of sweating on the same side of the face
may be seen. An anatomical localization of the neurological defect
is important as preganglionic lesions are frequently associated with
malignancy in the chest.
Fig. 2.29 Marcus Gunn (jaw-winking) ptosis is a congenital
syndrome characterized by elevation of the ptotic lid when the
mouth is opened or when the jaw is moved laterally, usually to the
side opposite the ptosis. The eyelid may even become retracted as
in this patient. The anomaly is due to a synkinesis between the
levator and the medial and lateral pterygoid muscles.
Fig. 2.30 Excessive upper-lid skin (dermatochalasis) is usually
the result of involutional changes involving the skin and may
present as pseudoptosis and occasionally as visual field loss. The
excess skin can be removed with a blepharoplasty. This patient has
marked brow elevation and frontalis overaction on both sides.
inferior rectus restriction, the retraction lessens in downgaze. The
most common cause of upper and lower lid retraction is
dysthyroid eye disease (Table 2.2). Treatment depends on the
cause. The vertical height of the palpebral aperture can be
reduced by excising Muller's muscle, recessing the upper lid
retractors or inserting a graft of material such as hard palate, ear
cartilage or artificial spacer material.
Table 2.2 Causes of upper and lower lid retraction
Mechanism
Mechanical Increased volume of orbital contents
Shortening of lid retractor complex
Neurogenic Supranuclear lesions of dorsal midbrain
(Collier's sign)
Oculomotor synkinetic syndromes
Myogenic Excess stimulation of Muller's muscles
and/or levator palpebral superiori s
Fig. 2.31 This patient has bilateral upper and lower lid retraction
resulting from dysthyroid eye disease (see Ch. 20) .
EYEliD TUMOURS
A wide variety of tumours can affect the lids. These arise
predominantly within the skin and originate mainly, but not
exclusively, from the epidermis, epidermal-associated structures
(eccrine and apocrine sweat glands, and pilosebaceous units),
epidermal melanocytes and from blood vessels and nerves within
the dermis. Tumours include cysts, choristomas, hamartomas
and neoplasms, and a number of inflammatory lesions and
cellular infiltrates, and can be classified as benign, premalignant
or malignant. For convenience and clarity, pigmented lid
tumours are considered separately.
Aetiology
Large globe, proptosis
Surgery, trauma or infiltration (e.g. thyroid, sclerosing tumours)
Inferior rectus restriction
Lateral and medial pterygoid synkinesis (Marcus Gunn syndrome)
Aberrant regeneration of the oculomotor nerve
Hyperthyroidism
Symp9thomimetic drugs (apraclonidine, phenylephrine)
Fig. 2.32 Patients with a unilateral ptosis may have an apparent
retraction of the contralateral upper lid due to increased neuronal
stimulation of this levator, according to Herring's law. When the
ptotic lid is elevated the excessive neuronal stimulation is relieved
and after a few minutes the retracted lid falls to a normal level.
The position and size of tumours should be recorded, ideally
photographically and, for lesions that may be malignant, any
associated lymphadenopathy must be documented. Lymphatic
vessels from the lateral two-thirds of the upper lid and the lateral
third of the lower lid drain into the superficial parotid nodes,
whereas those from the medial third of the upper lid and the
medial two-thirds of the lower lid drain into the submandibular
nodes. Tumours can often be identified by their clinical
appearance but on occasions biopsy may be necessary to confirm
or establish a diagnosis and to plan definitive treatment. All
excised lesions should be referred for histological examination.
 EYELID TUMOURS

BENIGN LID TUMOURS

Fig. 2.33 Xanthelasmas are infiltrates of lipid-laden histiocytes in

the dermis. They may be either idiopathic or associated with
hyperlipidaemia. Local treatment consists of excision or argon laser
ablation. Patients should be investigated for hyperlipidaemia.

:;:::;::::::o~:::::;,~===::::::=:===:=3 epidermis
--~
dermis

Fig. 2.34 Histological examination shows aggregations of lipid-laden histiocytes in the dermis in relation to blood vessels.

Fig. 2.35 Cysts of Moll are retention cysts of the apocrine glands
of Moll. They occur at the lid margin and appear translucent
because they are filled with clear fluid. They are treated by excision
or marsupialization.
 Fig. 2.36 Sebaceous cysts appear as yellowish-white lumps in the
skin and have a central occluded punctum. They are caused by
blockage of pilosebaceou s units and contain retained cheesy yellow
keratin. They can b e treated by simple excision.

ke ratinized stratified
squamous epithel ium
keratin within
forming cyst wa ll
cavity of cyst

Fig. 2.37 Sebaceous cysts contain keratin and are lined by keratinized stratified squamou s epithelium. Low (left) and high (right)
magnification.

Fig. 2.38 Cysts of Zeis arise fro m the glands of Zeis in the same
way as sebaceous cysts arise elsewhere. Like sebaceous cysts, they
contain keratin. They can be incised.
 EYELID TUMOURS

Fig. 2.39 Meibomian cysts (chalazions) are not true cysts. They are due to granulomatous inflammation caused by retained sebaceous
secretion leaking into the stroma of the lid following blockage of the meibomian glands in the tarsal plate. Clinically they sometimes
present in the acute stage as a red, tender swelling within the tarsal plate of the upper or lower eyelid (left). This either resolves completely
or leaves a firm nodule (right). Alternatively, they can present as a painless, non-inflamed lump in the tarsal plate. Treatment is initially
conservative with heat and local antibiotics, but if resolution does not occur incision and curettage are performed.

granuloma

lipid (fat) spaces

granulomatous
inflammation and
lipid (fat) spaces
in t arsal plate

Fig. 2.40 This eyelid shows a localized lesion in the tarsal plate;
higher magnification shows a granulomatous inflammatory reaction
to lipid which has been leached during processing to leave empty
spaces (fat spaces).
Fig. 2.41 Capillary haemangiomas are on e of the commonest lid tumours seen in infancy. They have a predilection for the upper lid and,
if large enough, may cause amblyopia. They may become more prominent when the child cries. Many involute sp ontaneously, as in this
child over 2 years, but intralesional steroid injections may sp eed up the process.

Fig. 2.42 Histological examination shows irregular capillary channels of varying size in the dermis and subcutaneous tissue.

Fig. 2.43 An eyelid neurofibroma may b e diffuse, as in this

patient, or localized (Fig. 2.1 8). Localized lesions may b e excised,
but large lesions require careful debulking. P lexiform
neurofibromas are u sually seen with type 1 neurofibromatosis. This
child also has partial hemihypertrophy of the face, ectropion uveae
and sphenoidal wing dysplasia.
 Fig. 2.44 Histological examination of a neurofibroma shows
proliferation of Schwann cells, fibroblasts and nerve axons with
wavy collagen fibres.

Fig. 2.45 A simple squamous cell papilloma is a benign overgrowth of squamous epithelium commonly found on the lids or lid margin
with a typical raspberry-like appearance (left). Keratin may build up on the surface of a squamous papilloma to form a cutaneous horn
(right). The lesion can be simply excised or cauterized.

hyperkeratosis

Fig. 2.46 This example shows a fibrovascular core with

overlying irregular acanthosis (thickened squamous cell layer)
and hyperkeratosis.
I RE EVELJOs

Fig. 2.47 Seborrhoeic keratosis (seborrhoeic wart, basal cell

papillorpa) occurs in the elderly as a benign, discrete and often
rather greasy and pigmented raised lesion. Other lesions are
frequently present elsewhere on the body.

Fig. 2.48 Histologically seborrhoeic keratoses are epidermal thickenings consisting mainly of basal cells. A characteristic feature is the
abrupt transition from basal cells to squamous cells and keratin production with the formation of keratin-filled cysts (horn cysts). The
amount of surface keratin is variable and the pigmentation seen clinically is due to melanin in the basal cells.

Fig. 2.49 A keratocanthoma is a rapidly growing, dome-shaped

lesion with a central core of keratin, most commonly seen on the
lower lid. It usually grows vigorously over a 3-month period and
then involutes spontaneously. Should involution not occur,
however, the lesion should be excised in its entirety for histological
identification as a small number may be confused with squamous
cell carcinoma.

shoulder

normal keratin-containing cup

epidermis l,t-,~::;-.,;

thickened epi dermis

Fig. 2.50 The histological diagnosis of a keratoacanthoma

depends largely upon an adequate clinical history as the
appearance can resemble a well-differentiated squamous cell
carcinoma. Microscopy shows epidermal thickening with a sharp
transition from normal to abnormal epidermis. There is well-
marked shoulder formation and a central keratin-containing cup.
 EYELID TUMOURS

LID TUMOURS WITH MALIGNANT POTENTIAL

Fig. 2.51 In clinical practice actinic (solar or senile) keratosis is

the most common precancerous skin lesion. It relates to excessive
solar radiation rather than age . It presents as a dry, scaly and
slightly raised lesion with excess keratin, mainly in elderly people
with fair skins who have been exposed to excessive sun. There is an
underlying squamous dysplasia that may eventually proceed to
invasive squamous cell carcinoma (see Figs 2.53 and 2.54) .
Lesions can be treated by excision or cryotherapy, depending on
size and location.

hyperkeratosis

Fig. 2.52 Histological examination shows either atrophy of the epidermis or acanthosis with squamous cell dysplasia and hyperkeratosis.
Elastotic degeneration (basophilic degeneration of collagen) is seen in the underlying dermis, and there is a chronic inflammatory cell
infiltrate.

MALIGNANT LID TUMOURS

Fig. 2.53 Squamous cell carcinoma may arise de novo or from a

pre-existing actinic keratosis or Bowen's disease (carcinoma in
situ), and is especially common in the rare syndrome of xeroderma
pigmentosum. The tumour has an everted edge and is relatively
more common on the upper eyelid. It may metastasize to the
regional lymph nodes. Treatment is usually by surgical excision.
 islands of proliferating
dysp lastic squamous 1-----+--
epitrelium infiltrating
dermis

Fig. 2.54 Microscopy shows downward proliferation of dysplastic squamous epithelium with invasion into the dermis.

Fig. 2.55 Basal cell carcinoma is the most common malignant

eyelid tumour. It usually arises on the lower eyelid or at the medial
canthus. Nodular, ulcerating and sclerosing (m orpheic) types are
seen. Treatment is by surgery, radiotherapy or cryotherapy
depending on the site of the lesion and the physician's preference.
Surprisingly, of tumours that are incompletely excised, only about
25 per cent will recur clinically. This is an example of a relatively
benign type of basal cell carcinoma with a classical pearly margin
laced with blood vessels and a central shallow ulcerated base.

tumour

strom a

Fig. 2.56 The tumour arises from the pluripotential germinative cells that form the basal layer of the epidermis. Areas of glandular or
squamous differentiation can be seen in some tumours. Palisading of cells at the periphery of tumour lobules is a common feature (right).
 EYELID TUMOURS 55

Fig. 2.57 This example of basal cell carcinoma shows a

sclerosing (morpheic) tumour with a less clearly defined margin.
At operation it is difficult to define the tumour margins, and this
type of lesion is best excised by Mohs' micrographic surgical
technique to ensure complete removal.

Fig. 2.58 Histological examination shows elongated strands of tumour cells embedded in a dense fibrous stroma.

Fig. 2.59 Basal cell carcinomas spread by direct extension and

may be highly invasive, although they do not metastasize. Local
invasion is a particular problem of tumours at the inner canthus as
these may involve the lacrimal drainage apparatus or nasal sinuses.
THE EYELIDS

Fig. 2.60 Meibomian gland carcinoma may occur in either a localized or a more generalized form . When the carcinoma is relatively
localized, it often presents as a persistent and recurrent meibomian cyst. These localized tumours, shown on the left, can be excised
surgically. The more generalized form (right) often presents as a severe unilateral and persistent chronic blepharitis. Diffuse disease
normally carries a poor prognosis and requires treatment with a combination of radiotherapy and surgery.

PIGMENTED EYELID LESIONS

Normal Ephilis Lentigo Junctional Compound Intradermal Blue

(freckle) naevus naevus naevus naevus

Epidermis
0

oo
oo
0 0
Dermis
0 0

Increased melanin Increased Increased Naevus cells Naevus cells Migration arrest of
normal numbers of melanocytes melanocytes forming migrating into in the dermis melanocytes from
melanocytes nests of dermis neura l crest
naevus cells

Fig. 2.61 All melanocytes are derived from the neural crest. Epidermal melanocytes can form naevus cells and so lead to the
development of junctional, compound and intradermal naevi. In contrast, dermal melanocytes can form blue naevi.
 EYELID TUMOURS

Pigmented lid lesions with malignant potential

nests of naevus cells

.:J'--2:::0:::.,~::if.~~'--l at epidermal-dermal
junction

naevus ce lls at
epidermal-derma l
junction and in dermis

epidermis

clear zone of
normal tissue

naevus cells
in dermis

Fig. 2.62 It is difficult to diagnose the naevus type by the clinical appearances. Junctional naevi can occur at the lid margin and are
usually flat and well circumscribed; the naevus cells lie at the epidermal- dermal junction (top). Compound naevi are raised, pigmented or
warty lesions occasionally with hairs on the surface. Histological examination shows, as in this example (middle), naevus cells at the
epidermal-dermal junction and within the dermis; there may also be a papillary configuration. Intradermal naevi present as dom e-shaped
nodules, papillomatous lesions or skin tags; they are frequently devoid of pigment and are often excised as 'papillomas'; naevus cells are
found only within the dermis; a clear zone of normal tissue separates them from the epidermis (bottom) .
 Fig. 2.63 Lentigo maligna presents as an irregular, flat, tan-
brown, variably pigmented patch, ranging in size from a few
millimetres to several centimetres. It has the potential of evolving
into a fully invasive malignant melanoma; the development of a
papular darker area often coincides with the histological findings of
invasion. Macules enlarge slowly over 5- 10 years. Between 10 and
25 per cent of all head and neck melanomas arise from lentigo
maligna.
By courtesy of Dr C M Lawrence.

Malignant pigmented lid lesions

Fig. 2.64 A malignant melanoma can arise de novo or from a pre-

existing junctional or compound naevus. Warning signs of
malignant change in a naevus are a rapid increase in size, satellite
lesions, ulceration or haemorrhage, but any pigmented eyelid lesion
that is growing should be excised. These examples show early
malignant change in a pre-existing naevus (left) and an advanced
malignant melanoma (right).

melanoma cells
infiltrating the
epidermis and
dermis

Fig. 2.65 Malignant melanoma comprises about 1 per cent of eyelid malignancies. Melanoma cells can be seen infiltrating both the
epidermis and dermis in this specimen. Tumours involving the lid margin and those that are more than 0.75 mm in thickness carry a poorer
prognosis; spread occurs through the lymphatics or bloodstream.
 EYELID TRAUMA

Fig. 2.66 Full-thickness loss of eyelid tissue, as in this case

following a caustic burn, may result in corneal exposure and
requires' sophisticated techniques of lid reconstructive surgery.
Conjunctival damage is often present, creating problems of
symblepharon and loss of ocular motility, dry eye or damage to the
lacrimal drainage system.

Fig. 2.67 Lateral traction injury to the eyelid may avulse it from the medical canthal tendon, lacerating the lacrimal drainage apparatus
without loss of lid tissue.

Fig. 2.68 Upper lid lacerations need to be explored carefully and the levator repaired if cut. A search should be made for a foreign body
within any perforating lid injury, and the globe must always be visualized and the fundus examined. This patient had a full-thickness lid
laceration with perforation of the globe from a broken bottle injury.
 Fig. 2.69 In this patient, severe injuries around the right orbit
have caused orbital wall fractures and avulsion of the medial
canthal tendon, resulting in a traumatic telecanthus. Such a severe
injury may also cause ptosis as in this case, either from direct
injury to the levator complex, injury to the nerve supply, or by
causing enophthalmus following a blow-out fracture.

Fig. 2.70 Nonaccidental injury. This child was burned on the lids with a cigarette. In suspected cases of nonaccidental injury, the child
should be formally assessed for retinal haemorrhages from throttling, skeletal injuries and healing fractures by a paediatrician experienced
in the medico-legal implications of diagnosis.
The Conjunctiva:
Diseases and Tumours
Frank Larkin~ Paul Hunter

The Normal Conjunctiva

Pathological Changes of the Conjunctiva
Drug-induced Changes
Chemical Burns
Nonpigmented Tumours of the Conjunctiva
Pigmented Lesions of the Conjunctiva
Z THE CONJUNCTIVA: DISEASES AND TUMOURS

The conjunctiva is the transparent mucous membrane lining the
inner surfaces of the eyelids; it is reflected over the anterior
episclera and sclera before terminating at the limbus, where it is
continuous with the corneal epithelium. In the embryo the
conjunctiva develops from the ectoderm covering the lids and
surface of the globe, and is formed during the third month of
intrauterine life as the eyelids grow together. A healthy
conjunctiva is essential for normal ocular function and together
with the eyelids it is critical in maintaining a suitable
environment for the cornea to function as the primary refractive
element of the eye. Its mucous and accessory lacrimal secretions
are important components of the precorneal tear film, and their
deficiency gives rise to tear film instability and p oor wetting of
the corneal surface, which may lead eventually to pathological
changes in the cornea. It follows, therefore, that examination of
the whole conjunctival surface is necessary in order to interpret
signs in the cornea, and an understanding of conjunctival
pathology is a prerequisite to the effective management of many
corneal disorders. As part of its function in maintaining the
corneal environment, the conjunctiva also has an important role
in defending the eye against a variety of agents.

THE NORMAL CONJUNCTIVA

r -- - - - - Posterior conjunctival
artery

Anterior cil iary artery ----->;.,~

_ . - - - - Peripheral palpebral
Superior rect us muscle - --f',e;/ arcade

Marginal palpebral
arcade

//"llT" " - -- -
H - - + - - - - Tarsal
~~~;;nal} z ones
/.'<---t'-----t---- - - - Orbital
.&-----:f--+- - - - Fornix

Fig. 3.1 The conjunctiva is comprised of a bulbar portion covering the anterior part of the globe (except for the cornea) and two
palpebral portions that cover the posterior aspects of the upper and lower eyelids. The palpebral and bulbar conjunctiva are continuous
through the upper and lower fornices. The blood supply of the conjunctiva is derived mainly from that of the eyelids, with some
contribution from the anterior ciliary vessels in its bulbar portion through the limbal plexus. The nerve supply is mainly from the
ophthalmic division of the trigeminal nerve but a variable proportion of the inferior conjunctiva is supplied by branches of the maxillary
division.

,d'
episcleral vessels f-----7"-----.:'1

limbal arca de of
subconjunctival blood vesse ls
vessel

Fig. 3.2 The bulbar conjunctiva is normally transparent making the subconjunctival and episcleral blood vessels easily visible. Its
anterior limit is the limbus where the epithelium becomes continuous with that of the cornea. The normal limbal arcade of blood vessels
(formed by anastomosis of the terminal branches of the posterior conjunctival and anterior ciliary vessels) may extend a short distance on
to the cornea but in so doing terminates in an even border on the clear cornea.
 THE NORMAL CONJUNCTIVA 63

bulbar conjunctiva

lower fornix
grey line
(anterior edge of m---""~~
mucous membrane) ''""''"" '="' lower ta rsus

Fig. 3.3 The lower palpebral conjunctiva may be readily inspected by gentle downward traction on the lower eyelid. It is slightly thicker
than the bulbar conjunctiva and is highly vascular, especially in its tarsal portion where it derives its blood supply from the tarsal arcades.
The lower fornix itself has few blood vessels but a larger amount of lymphoid tissue and mucus-secreting glands.

,,
,~'

ascending
branches from f=___,..,.L--:;r,:;.:._--<> ,
marginal arcade descending branches
-"-7~"'--i from peripheral
palpebral arcade

Fig. 3.4 The upper tarsal conjunctiva is inspected by everting the upper eyelid. As in the lower lid, it is firmly adherent to the underlying
tarsal plate. The blood supply is derived from the palpebral arcades, of which the branches are readily visible. A small number of lymphoid
follicles can often be seen at the medial and lateral aspects of its upper border.

ascending branches
of peripheral LS---c-----"c::--",
palpebral arcades

Fig. 3.5 The upper fornix is visible only on double eversion of the upper eyelids using Desmarres' retractor. Here the posterior
:onjunctival vessels are visible and interspersed with yellowish patches of inactive lymphoid tissue. It is particularly important to examine
me upper fornix when searching for foreign bodies or in cases of suspected chlamydia! conjunctivitis when enlarged follicles are seen (see
Ch. 4).
4 THE CONJUNCTIVA: DISEASES AND TUMOURS

goblet cell s

non-ke ratinized stratified

squamous epith elium
substantia propria
... ··"<:::5

Fig. 3.6 The microscopic anatomy of the conjunctiva shows it to consist of non-keratinized stratified squamous epithelium overlying a
substantia propria. In its tarsal portion, the connective tissue elements of the latter form a fine network creating a papillary structure,
but towards the fornices it is looser and contains elastic fibres, blood vessels and lymphoid tissue . In addition, the conjunctiva contains
numerous goblet (mucus-secreting) cells, especially in the fornices, and the accessory (lacrimal) glands of Krause and Wolfring.

SURFACE CELL MORPHOLOGY

The morphology of the surface cells of the conjunctiva may be remain adherent and can be stained histologically with periodic
examined in vivo by impression cytology. This technique involves acid-Schiff (PAS) or haematoxylin to make a quantitative and
the application of a strip of filter paper to the area of conjunctiva qualitative assessment of the conjunctival epithelium.
under investigation. Upon removal of the strip, the surface cells

goblet cel ls

epit helial ce lls

Fig. 3. 7 The characteristic morphology of the bulbar conjunctiva

cells can be seen with numerous mucus-secreting goblet cells
interspersed between the polygonal, rather irregularly arranged,
epithelial cells.
By courtesy of Professor Noel Dilley.

Fig. 3.8 An impression taken from the tarsal conjunctiva shows

normal conjunctival epithelial cells, but no goblet cells are present.
Impression cytology is useful in differentiating changes in the
conjunctival cell population in health and disease .
By courtesy of Professor Noel Dilley.

PATHOLOGICAL CHANGES OF THE CONJUNCTIVA
The conjunctiva may undergo a variety of changes as a result of
disease . Recognition of the types of change may give valuable
information about the aetiology of the disease, but the
conjunctiva has a limited repertoire of pathological responses and
great care should be exercised before attributing particular
conjunctival signs to a diagnosis. It is rare for pathognomic
Table 3.1 Causes of papillary and follicular conjundivitis
Papillae
Allergic conjunctivitis : atopic, vernal, seasonal or perenn ia l
Topical preparations: drops, preservatives, ointments
Chron ic irritation: giant papillary conjunctivitis, superior
limbic conjunctivitis, dry eyes
Fig. 3.9 Hyperaemia of the conjunctiva may occur as part of any
acute inflammatory process or in response to chronic irritative
factors . There is an increase in the number, calibre and tortuosity
of the vessels, producing a characteristic bright red appearance.
Hyperaemia is often associated with increased vascular
permeability and oedema or cellular infiltration.
PATHOLOGICAL CHANGES OF THE ONJUNCTIVA
findings to occur in the conjunctiva: diagnosis should always be
based on the history and on examination of the adjacent tissues
such as the lids and cornea in addition to the conjunctiva.
Causes of papillary and follicular conjunctivitis are listed in
Table 3.1.
Follicles
Vi rus infecti on: adenovi rus, herpes simplex, molluscum contagiosum
Ch lamydia ! infection: t rachoma (subtypes A-D), paratrachoma (subtypes E-K)
Drug induced: glaucoma, antiviral drops
Lymphoid disease: reactive hyperp lasia, conjunctival lymphoma
loss of conjunctival
vessels
edge of avascular
zone
Fig . 3.10 Avascularity of the conjunctiva occurs as a result of
vascular endothelial damage to the conjunctival vessels from toxic
or .chemical insult. The affected conjunctiva is blanched. ;c-
Depending on the degree of penetration of the chemical agent, the
episcleral and scleral vessels may be spared, as in this example.
Such changes are most commonly seen acutely following alkali
burns but may also follow subconjunctival antibiotic injections or
prolonged use of topical antiviral preparations, as in this case,
resulting from trifluorothymidine administration, an antiviral agent
once used to treat herpes simplex keratitis.
6 THE CONJUNCTIVA: DISEASES AND TUMOURS

conjunctival
haemorrhage

Fig. 3.11 Congestion of the conjunctival vessels arises as a result

of impaired venous drainage or increased permeability which, if
severe, may produce oedema of the conjunctiva (chemosis). The
characteristic dusky red coloration results from increased vascular
stasis within the conjunctiva. Chemosis without venous congestion
occurs most commonly in association with acute allergic states
when the pale swollen conjunctiva takes on a jelly-like appearance
(see Fig. 5.2).

su bconJunct ival
haemorrha ge

post erior limit

Fig. 3.12 Subconjunctival haemorrhages most frequently arise

spontaneously and appear as red patches extending to the limbus.
They may result from an episode of raised venous pressure (e.g.
following coughing) or from trauma and very rarely from blood
dyscrasias or vessel anomalies. With head trauma, if no posterior
limit to the haemorrhage is defined, the blood may have resulted
from a middle or anterior cranial fossa fracture and patients should
be examined with this in mind .

Fig. 3.13 Papillary hypertrophy is caused by the conjunctiva

being thrown into folds and characterizes the subacute stage of
many types of inflammation. Basically, the papillae represent a
vascular response with an exaggeration of some aspects of the
normal conjunctival anatomy. Clinically they can be recognized as
small elevations of the conjunctiva that produce a slightly granular
or velvety appearance. They break up the smooth glistening light
reflex of normal conjunctiva. In this example, t~e minute surf~c~
U;_regularity produced by the individual papillae are highlighted in
the light reflex laterally. Each papilla contains a central dilated
arteriole with a surrounding clear or slightly infiltrated zone of
swollen conjunctiva. Usually, papillae can be seen only on
biomicroscopic examination, but in some chronic conditions giant
papillae may form that can be seen with the naked eye.
Fig. 3.14 Histologically, the conjunctiva between individual papillae is tethered to the underlying tarsal plate by the fibrous network
normally present in the substantia propria, and the papillae are produced by oedema, cellular infiltration and vasodilatation within the
spaces of this meshwork. Many chronic inflammatory cells are present.

Fig. 3.15 The clinical appearance of follicles is of large pink or

pale grey elevations lying beneath the conjunctival epithelium with
small blood vessels frequently visible on their surface. In the early
stages, they are present only in the fornices but may extend on to
the tarsi if the disease becomes chronic. Follicles are associated
particularly with conditions in which cell-mediated immune
mechanisms are involved, such as viral infections and drug
hypersensitivity. They can be seen in normal conjunctiva in
childhood.

conjunctival
epithelium ~'-"-----4+1--~ lymphoid germ inal
fol licles

Fig. 3.16 Conjunctival follicles are collections of lymphoid germinal follicles in the subepithelial stroma with immature cells centrally and
mature cells peripherally.
THE CONJUNCTIVA: DISEASES AND TUMOURS

Fig. 3.17 Pseudomembrane formation on the surface of the conjunctiva is seen in patients with severe acute conjunctivitis. A coagulum
of fibrin and proteinaceous exudate forms, and is initially loosely adherent to the underlying tissues from which the pseudomembrane may
be separated without causing bleeding from the surface. A true membrane is firmly adherent to the conjunctival epithelium and attempted
removal gives rise to a bleeding conjunctival surface. Subsequent organization of the membrane produces scar tissue .

Fig. 3.18 Conjunctival scarring may be the end-result of a wide variety of inflammatory processes. Its effects on the eye vary from
insignificant to devastating, depending on its effects on the tear film and lid architecture. Subepithelial fibrosis is seen as white tissue,
usually with associated distortion of the overlying superficial blood vessels. Localized superficial linear scarring may have little clinical
significance, as in this example, which followed a severe viral conjunctivitis.

areas of active
fibrovascular
proliferation l-c:'::'""f'--;--.,;~~~

Fig. 3.19 Extensive diffuse scarring (resulting from trachoma in this case) may have serious effects on the eye by diminishing the
protective functions of the lids and conjunctiva. Contraction of the scar may result in entropion, trichiasis and lid shortening. Obliteration
of the normal mucus-secreting cells may affect the stability of the tear film. This example also shows some fibrovascular proliferation in the
superficial scar tissue; subsequently this may add to the already extensive scar by further fibrosis (see also Ch. 4).
 PATHOLOGICAL CHANGES OF THE CONJUNCTIVA

,,
\\\' '.:I

Fig. 3.20 Symblepharon is an adhesion between the conjunctiva covering the lids and the globe, In this example, severe conjunctival
adhesions developed following an alkali burn, Disorders of ocular motility and poor lid closure with corneal exposure or instability of the
tear film may result.

keratin on tarsa l conjunctiva

lid margin

dry metaplastic
surface

Fig. 3.21 Squamous metaplasia of the conjunctiva can be recognized clinically by altered wetting characteristics of the affected
conjunctiva. Such changes usually arise as a result of prolonged chronic inflammation and eventually lead to keratinization which may
cause further damage to an already compromised cornea.

Fig. 3.22 A paralimbal mass alters the tear film and, in particular, causes a meniscus and thinning of the tear film over the adjacent
limbus and cornea. This can lead to localized corneal drying, thinning and epithelial ulceration, known as a dellen. The condition resolves
on treatment or removal of the lump.
70 THE CONJUNCTIVA: DISEASES AND TUMOURS

Fig. 3.23 Concretions are minute, hard, yellow spots seen in the palpebral conjunctiva of elderly people, although they may also be the
result of chronic inflammatory disease . They rarely cause symptoms but, if large, they occasionally project through the surface of the
conjunctiva to produce a foreign body sensation and will stain with Bengal Rose or fluorescein . If necessary, they may be removed using a
needle point under topical anaesthesia. Concretions are formed by cellular degeneration when the debris remains trapped in small recesses
of the conjunctiva and becomes calcified.

Fig. 3.24 Conjunctival retention cysts are common and usually

develop in the accessory lacrimal glands of Krause. These are thin-
walled cysts filled with clear watery fluid and usually do not cause
any symptoms. If large, they may be ruptured or excised.

DRUG-INDUCED CHANGES

The normal conjunctiva- and cornea can undergo changes in
response to toxicity from topical or systemic drugs or other
chemicals, in the absence of overt inflammation. Many old
topical medications contained silver or mercury which were
deposited in the conjunctiva; these are no longer used, but toxic
changes can be seen with topical antibacterial or antiviral drugs
if given for prolonged periods. In the cornea this is seen as
punctate epithelial erosions or a persistent epithelial defect and in
the conjunctiva as a papillary reaction, keratinization or puncta!
stenosis. Preservatives in eye drops can frequently induce
problems, particularly in eyes with tear film abnormalities or
when the drops are given for long periods of time. Such
abnormalities normally resolve on ceasing treatment or
substituting a preservative-free preparation.
Contact hypersensitivity reactions may arise m the
conjunctiva or eyelids from a wide variety of agents but are
commonly related to the use of cosmetic preparations, contact
lens solutions or topical medications (eye drops or ointments).
Substances may also be transferred to the periocular tissues
from the hand by means of eye-rubbing or contact with
bedlinen. The skin changes on the eyelids resemble those of a
contact dermatitis, whereas in the conjunctiva there is primarily
a follicular response. Symptoms include redness, irritation,
discharge and, especially, itching of the eye. Patients may also
complain that symptoms are most marked immediately after
application of the drop or ointment. The pathogenesis involves
delayed (cell mediated) hypersensitivity; the condition evolves
gradually over several days or weeks unless previous
sensitization has occurred, in which case its onset may be much
more acute.

punctate
epithelial erosions H,-t-'c:--\c\----cf-----

confluent
epithelial erosions f----f-----"".,-----

Fig. 3.25 Superficial punctate erosions on the cornea are a common feature of drug toxicity. The patient usually has a mildly red,
inflamed eye with some discomfort. The erosions are usually more pronounced over the inferior cornea where the exposure to the topical
drug is greatest. They stain with Bengal Rose or fluorescein.
By courtesy of Mr M G Falcon.

keratin

-~"""""--.J loss of
meibomian orifices

Fig. 3.26 This patient has developed squamous metaplasia of the conjunctival surface near the lid margin, following prolonged
idoxuridine therapy, once used to treat herpes simplex keratitis. A thick, white, keratin plaque is present, with the normal conjunctival
mucous membrane replaced by stratified squamous epithelium which has obliterated the meibomian orifices along the lower lid margin.
72 THE CONJUNCTIVA: DISEASES AND TUMOURS

-~--'1--1.--U loss of
hyperaemic carunc le
conjunctiva

site of punctum

Fig. 3.27 Dyskeratotic changes are seen over the whole of the
lower fornix and tarsus with extension on to the bulbar conjunctiva
on the medial side in this unusual example in which pilocarpine
and neutral adrenaline (epinephrine) drops had been used over
many years. Keratin sheet formation is seen as a whitish,
nonwetting surface in the areas of conjunctiva that might be
expected to have had most contact with the drug. The lower
punctum appears to have been completely obliterated and the
remaining visible conjunctiva is hyperaemic.

Fig. 3.28 Topical aminoglycoside antibiotics can cause bulbar

conjunctival ischaemia, as in this case following several weeks'
administration of tobramycin. This change reverses after cessation
of the drug.

Fig. 3.29 This patient with atopic keratoconjunctivitis has inferior periocular dermatitis following treatment of both eyes with ointment
(left). As is characteristic, the skin became less erythematous and tender within days after the ointment was discontinued (right) .
 Fig. 3.30 In a more severe reaction, such as in this case where
the patient was given antibiotic ointment to the right eye, the
swelling and erythema are more marked, the area of involvement is
more extensive and the skin has a weeping eczematous appearance.

Fig. 3.31 A wide range of topical medications such as antibiotics and antiglaucoma preparations, such as brimonidine and preservative
agents can produce a follicular response, most commonly seen in the inferior fornix. Reversal of the changes occurs over a period of several
weeks when the patient is changed to treatment with a preservative-free solution or an alternative drug.

Fig. 3.32 Bulbar follicles are frequently seen in drug hypersensitivity reactions. This figure shows a typical grouping of bulbar follicles at
the limbus of a sensitized patient who has recommenced treatment with trifluorothymidine drops (once used to treat herpes simplex
keratitis).
By courtesy of Dr A H S Rahi.
74 THE CONJUNCTIVA: DISEASES AND TUMOURS

CHEMICAL BURNS

Acid burns coagulate and precipitate the superficial proteins of
the conjunctiva and cornea; they do not penetrate the eye and so
tend to cause only superficial scarring. In contrast, alkalis
saponify the lipid in cell membranes and rapidly penetrate the eye
producing devastating damage to both blood vessels and
intraocular structures within minutes of contact. First-aid
measures, especially prompt immersion of the eye in cold water
or irrigation of the conjunctiva with bicarbonate solution to
dilute and remove the alkali are vital in reducing damage. Alkali
burns are followed by collagenase secretion from the limbal
conjunctiva in the recovery phases; this may produce corneal
melting and is compounded by destruction of the accessory
lacrimal glands and goblet cells in the conjunctiva, producing
tear film abnormalities. Corneal ulceration is the most serious
complication of chemical injury and can lead to perforation.
Decreased collagen synthesis is associated with local ascorbate
defiCiency and keratocyte loss. Damage to the limbus results in
delayed epithelialization with conjunctiva-derived epithelium
resulting in a vascularized opaque corneal surface and very poor
prognosis with corneal transplantation. Surgical management of
these eyes involves either autologous or donor limbal stem cell
transplantation (see Ch. 6).

Fig. 3.33 This patient shows acute changes in the skin and outer
eye immediately after an ammonia burn. There are large sloughing
areas with erythema of the skin of the upper and lower eyelids. The
conjunctiva is chemotic and haemorrhagic and there is loss of
corneal epithelium over the lower half of the cornea .

edge of
""-=--~~ corneal
loss of conjunctival epithelium
vasc ular pattern

Fig. 3.34 This is the appearance of the bulbar conjunctiva immediately after a severe alkali burn, showing the typical appearance with
complete absence of the normal conjunctival vascular markings in a dense, white, slightly chemotic conjunctiva. There is complete loss of
the whole corneal epithelium and early sloughing of necrotic conjunctiva beneath the upper tarsus.
By courtesy of Professor R J Buckley.
 edge of
-----==,...,..-----'-! slough ing
conjunctiva

Fig. 3.35 In the same patient as Fig. 3.34, there is extensive

conjunctival necrosis 3 weeks after the ammonia burn. The whole
upper tarsal conjunctiva is pale, yellowish and swollen, with poorly
defined vessels. The upper edge is starting to slough away from the
underlying tissues. Healing will occur with fibrosis of the lid
leading to cicatricial entropion, tear film deficiency and further
corneal damage.
By courtesy of Professor R J Buckley.

Fig. 3.36 The corneal changes of the same patient are shown 6
weeks later. The corneal stroma has become oedematous and is
undergoing melting, as evidenced by the ectatic shape and
peripheral guttering. There is failure of epithelialization over the
central part of the cornea.
By courtesy of Professor R J Buckley.

Fig. 3.37 Loss of the limbal stem cells leads to healing with
dysplastic epithelium derived from the conjunctiva. In this eye
there is massive neovascularization of the cornea with diffuse
stromal scarring associated with thinning and faceting of the
cornea. The corneal problems are usually compounded by
abnormalities in the tear film from the conjunctival damage; this,
together with the neovascularization, produces an extremely poor
prognosis for corneal grafting.
By courtesy of Dr A H S Rahi.
 IHE COI'JJOI'JC IIVA: DISEA SES A ND I OMOORS

NONPIGMENTED TUMOURS OF THE CONJUNCTIVA

Tumours of the conjunctiva occur infrequently and may cause
diagnostic problems at presentation. The clinical differentiation
between hypertrophic and neoplastic processes, and between
benign and malignant conditions, may be extremely difficult on
the basis of a single examination. Repeated observations over a
period of time with the aid of serial photographs may be helpful
in determining the evolution of the lesions; in many cases a biopsy
will be required to make a pathological diagnosis.
Tumours may be classified, according to their tissue of origin,
into those arising from the surface epithelium (or its associated
glandular elements), connective tissue, vascular tissue, lymphoid
tissue or peripheral nerves. Some common conjunctival tumours
are listed in Table 3.2. Pigmented lesions ofthe conjunctiva are an
important group of conditions that are considered in detail
separately.

Table 3.2 Common conjunctival tumours

Cell/tissue of origin Benign Malignant
Epithelium Hyperp lasia, papilloma, CIN* Squamous cell carcinoma
Vascular Haemangioma Kaposi's sarcoma
lymphoid system Reactive lymphoid hyperplasia Lymphoma
Nerve Neurofibroma
Melanocytic Naevus, melanocytosis Melanoma

*CIN (conjunctival intraepithelial neoplasia)

Fig. 3.38 Dyskeratosis is a feature of dysplasia, now known as conjunctival intraepithelial neoplasia (CIN); this encompasses a variety of
pathological changes seen in the conjunctival and corneal epithelium which may present clinically as a dry white plaque on the surface of
the globe (leukoplakia). The disorder may arise as a result of chronic irritative factors such as solar radiation and topical drug therapy; it
may also be due to human papilloma virus infection. This dry, keratinized, white plaque shows clearly against the chronically inflamed
conjunctiva which has- taken up fluorescein stain.
Fig. 3.39 The limbus and interpalpebral aperture are the commonest sites for CIN which may develop over a pinguecula or pterygium.
Such lesions should be excised if there is any suspicion of malignancy.

Fig. 3.40 Risk factors for malignancy are solar exposure and human immunodeficiency virus (HIV) infection. Malignant change is
suggested by the development of feeding vessels and increased bulk. Tumours can invade the orbit, but invasion of the eye is uncommon.
,8 THE CONJUNCTIVA: DISEASES AND TUMOURS

th ickened dysplastic
conj unctiva l epithelium

thicke ned dysplastic

conjunctival epithel ium

Fig. 3.41 C IN - low and high magnification. The lesions show dysplastic changes throughout the full thickness and are thus CIN stage 3
(carcinom a in situ) .

downward proliferation
of mal ignan t epithelial
cel ls

Fig. 3.42 H istological appearance of a moderately well-differentiated squamous cell carcinoma with downward proliferation of malignant
cells.
po NONPIGMENTED TUMoURS oF TAE CONJONt"TIVA

Fig. 3.43 Papillomas arising in the conjunctiva may be either sessile or pedunculated lesions with a slightly irregular surface. They occur
most commonly in patients over 40 years of age either at the caruncle or in the fornices, and are occasionally found in the lacrimal
canaliculi or lacrimal sac. They may occasionally be multiple. This is an example of a sessile papilloma on the bulbar conjunctiva.
Treatment is by excision and should, where possible, include an area of healthy conjunctiva around the base.

non-keratini zed
stratifi ed squamous 1----------,.4
epithelium

Fig. 3.44 Histological examination shows fingers of non-
keratinized stratified squamous epithelium around a central
fibrovascular stalk. Goblet cells are present within the proliferating
epithelium. Human papilloma viruses are implicated in the
pathogenesis.
Fig. 3.45 Limbal dermoids are congenital tumours of
mesodermal and ectodermal origin. They appear as raised,
circumscribed, pale yellowish lesions and are generally situated at
the lower temporal limbus where they involve the cornea,
conjunctiva and sclera. They are normally present at birth and,
although enlargement is unusual, removal may be justified on
cosmetic grounds when the child is nearing school age. If the
deeper layers of the cornea are involved, a lamellar keratoplasty
may be required to restore corneal thickness and reduce
astigmatism.
I HE COI'JJOI'JC I IVA! DISEASES AND I OMOURS

stratified squamous
-----:::=--.,J epithelium
"7!'--------------l hair follicle
':2~-----"":R'"l sweat gland ducts

-+-cc+-:=-----l collagen

'---":::r--~ sebaceous glands

Fig. 3.46 Limbal dermoids are solid rather than cystic. Histological examination shows dense collagenous tissue with dermal elements
covered by stratified squamous epithelium. A variety of tissues may be present within the collagen matrix, as in this example, where islands
of sebaceous glands, sweat gland ducts and a hair follicle are visible.

Fig. 3.47 Children with limbal dermoids should be examined for other signs of Goldenhar's syndrome (first branchial arch syndrome-
accessory auricles, limbal and orbital dermoids, sometimes with maldevelopment of the jaw).

caruncle

Fig. 3.48 Orbital dermolipomas may occur as part of Goldenhar's syndrome or in isolation.

Fig. 3.49 This small haemangioma of the conjunctiva had been present for many years with no alteration in size. The dilated blood vessels
reflect the vascular nature of the lesion and should be distinguished from the enlarged feeding vessels associated with malignant tumours.
 Fig. 3.51 Histological examination shows proliferating spindle-
shaped endothelial cells with vascular spaces and a chronic
Fig. 3.50 Kaposi's sarcoma is a multicentric tumour thought to inflammatory cell infiltrate.
be of vascular endothelial cell origin. It was rare until the advent of
HIV infection in which it is related to infection with herpes virus
type 8. Mucous membrane involvement, as in this example, in the
conjunctiva, is usually a later manifestation of the condition,
although about 20 per cent of patients with Kaposi's sarcoma show
conjunctival involvement. The lesions appear as bright red or
purplish fleshy masses and haemorrhages are frequently present
within the tumour reflecting the highly vascular nature of the
condition. They are radiosensitive and can therefore be treated by
radiotherapy if they become large and bulky.
By courtesy of Mr Bruce Mathalone.

lymphoid hyperplasia

Fig. 3.52 Reactive lymphoid hyperplasia and lymphoma cannot be distinguished from each other on clinical findings. Reactive lymphoid
hyperplasia presents as a slowly growing, diffuse mass involving the bulbar conjunctiva and fornices. There are no inflammatory changes in
the unaffected normal-appearing conjunctiva and therefore the condition should not be confused with lymphoid follicles seen in cases of
conjunctivitis.
 E CONJUNCTIVA: DISEASES AND TUMOURS

large and
co nfluent folli cles

Fig. 3.53 Conjunctival lymphoma involving upper (left) and lower (right) fornices. Large follicular masses usually involve the fornices in
both eyes. The histological appearance of conjunctival lymphomas is complex and monoclonal antibodies and molecular genetics are
necessary to distinguish reactive lymphoproliferation from lymphoma. Conjunctival lymphomas are usually B-ee!! tumours arising from the
mucosa-associated lymphoid tissue (MALT) system, and are known as 'maltomas'. Assessment for orbital and extraocular systemic
lymphoma is required. Lymphomas restricted to the conjunctiva respond well to radiotherapy and have a good prognosis.

PIGMENTED LESIONS OF THE CONJUNCTIVA

The melanocytes of the conjunctiva are derived from the neural
crest, as are those of the skin and uveal tract. A wide variety of
pigmented conjunctival lesions is seen clinically. They can be
difficult to diagnose and have varying degrees of malignant
potential. Conjunctival naevi are usually thought of as congenital
lesions, although they are frequently not apparent at birth and
tend to become larger and more pigmented with age. Junctional
and compound conjunctival naevi have a low malignant
potential. About 60 per cent of conjunctival melanomas arise in
a naevus or in an area of primary acquired conjunctival
1
melanosis. On examination, junctional, compound and
subepithelial naevi and primary acquired melanosis, move with
the conjunctiva but deep conjuctival m elanocytic lesions do not.
Conjunctival naevi are similar to cutaneous naevi but with two
important differences: the conjunctiva has no dermis, hence
'subepithelial' replaces 'dermal' in the terminology; also naevus
cells migrating down into the subepithelial tissue may be
accompanied b y surface epithelial cells and if goblet cells are
present mucinous cysts m ay form. Most conjunctival naevi are
compound which have a low malignant potential.
 PIGMENTED LESIONS OF THE CONJUNCTIVA

CLASSIFICATION OF PIGMENTED LESIONS OF THE CONJUNCTIVA

3.54 Conjunctival naevi, although congenital, are not always present at birth and in many cases may not become apparent until they
pigmented in adulthood. They are common benign lesions, often seen at the limbus . In this example the pigmented area in the
conjunctiva contrasts markedly with the white sclera. They tend to grow slowly but, provided they do not undergo rapid change,
feeder vessels or become raised, no treatment is required.

naevus

Fig. 3.55 The caruncle is another common site for conjunctival

naevi.

surface epithelium

naevus cells

subepithelial mucinous
cysts

Fig. 3.56 Histological examination shows a naevus with

subepithelial mucinous cysts.
THE CONJUNCTIVA: DISEASES AND TUMOURS

Fig. 3.57 This child has an extensive benign naevus involving the
conjunctiva, caruncle and eyelids. (Note the full-thickness skin
graft medially to the upper and lower lids.)

MELANOSIS

Congenital melanosis is common in eyes of black patients. It is
either epithelial where it appears as localized pigment flecks or
subepithelial where it is diffuse and may be associated with scleral
and uveal pigmentation (ocular melanocytosis - melanosis oculi).
Ocular melanocytosis together with ipsilateral lid and
periorbital skin pigmentation (blue naevus) comprises
oculodermal melanocytosis (naevus of Ota). This is a unilateral
slate grey discolouration of the sclera that is associated with
increased pigmentation of the lid skin and uveal tract. There is no
increased risk of malignancy in the lids or conjunctiva but
patients with melanosis oculi do have an increased risk of uveal
melanoma (1 : 400), probably due to increased numbers of
melanocytes in the uveal tract.
Acquired melanosis may be due to a variety of causes such as
exposure or drugs but primary acquired melanosis of the
conjunctiva, which is akin to lentigo maligna of the skin, carries
a high risk of the patient developing multiple malignant
conjunctival melanomas. Although malignant melanomas of the
conjunctiva will invade locally and metastasize to the regional
lymph nodes, their growth tends to be slow; small lesions do well
with local treatment, especially cryotherapy.

dark brown
iris

----.J pigmented
lid skin

Fig. 3.58 A naevus of Ota is a blue naevus of the sclera and periorbital skin together with a diffuse naevus of the uvea . This example
shows a large bluish-grey area of scleral pigmentation extending up to the limbus with an edge that is slightly mottled. Unlike conjunctival
naevi this lesion does not move with the conjunctiva. The iris was darker than that in the fellow eye, indicating an associated or diffuse
naevus of the uvea.
 PIGMENTED LESIONS OF THE CONJUNCTIVA 85

Fig. 3.59 _ Secondary acquired melanosis associated with long-

standing conjunctival disease is shown in this case of ectropion in a
black patient. Similar pronounced pigmentary changes may be
seen in the conjunctiva of patients with radiation, trachoma or
allergic conjunctivitis and probably reflect the high rate of
conjunctival epithelial turnover associated with chronic disease.
The condition is not premalignant.

MALIGNANT MELANOMA OF THE CONJUNCTIVA

Fig. 3.60 Malignant melanomas of the conjunctiva may arise

spontaneously from a pre-existing junctional or compound naevus,
or from an area of primary acquired melanosis. They occur with
equal frequency in males and females, most commonly between
the ages of 40 and 60 years. This is an example of a malignant
melanoma arising at the limbus and spreading into the cornea.
Many feeding blood vessels are visible. Localized lesions may be
treated by excision of the affected conjunctiva with a wide margin
of tissue . The prognosis is most dependent on the location, fornix
involvement being associated with the worst outcome .

•
Fig. 3.61 This eye shows multiple malignant melanomas of the
conjunctiva arising in areas of primary acquired melanosis. This
rare unilateral condition is seen in Caucasian eyes with onset in
middle age and a protracted course of lesions slowly enlarging in
area over many years with increasing atypical melanocytic
hyperplasia. About 20 per cent of lesions become malignant. The
condition is analogous to lentigo maligna of the skin. All patients
should be followed at regular intervals with serial photography.
Pigmented areas that increase in size or thickness or develop
feeding vessels should be excised and examined histologically for
evidence of malignancy. Small lesions can be treated by
cryotherapy.
6 THE CONJUNCTIVA: DISEASES AND TUMOURS

Fig. 3.62 Malignant melanomas may spread by direct invasion or by seeding to other parts of the conjunctival sac. In this example a
melanoma on the upper tarsus has given rise to lesions at the lid margin and the upper limbus. In this instance exenteration of the orbit,
with the eyelids, offers the only sure way of surgically removing all tumour-bearing tissue .

Fig. 3.63 This gross example of a neglected maJignant

melanoma shows a fungating tumour that has arisen from the
anterior part of the globe and spread on to the cheek. In spite of its
size, there was no direct invasion of neighbouring orbital or facial
structures and no evidence of distant metastases.

surface epithelium

melanoma cells in
subepithelial stroma

Fig. 3.64 Histological examination shows sheets of melanoma cells in the subepithelial stroma. Conjunctival melanomas have features
similar to those of cutaneous melanoma . Tumours less than 1.5 mm in thickness and those on the bulbar conjunctiva carry a better
prognosis than tumours on the tarsal conjunctiva.
Infections of the Outer
Eye
Frank Larkin, Paul Hunter

Viral Infections
Chlamydia! Infections
Bacterial Infections
Parasitic Diseases and Infestations

'
INFECTIONS OF THE OUTER EYE
VIRAL INFECTIONS
Viruses are a common cause of infection of the external eye
where they produce a wide variety of disease ranging from mild
transient conjunctivitis to more serious infections in which
conjunctival or corneal involvement may lead to scarring and, in
some cases, blindness. Adenovirus, picornavirus, herpes simplex
virus and varicella zoster virus may all cause isolated
conjunctivitis, but commonly patients have some corneal or
eyelid involvement, thus serving to remind the clinician that the
whole of the external eye and adnexae may be a target for the
same infection. The spread of the virus to the eye may occur by
direct inoculation from an infected source, from indirect
ADENOVIRUS
Adenovirus infection may be due to a variety of different
serotypes that can vary in their clinical presentation and
epidemiology. Epidemic keratoconjunctivitis is associated with
adenovirus serotypes 8 and 19, which produce a severe and
highly contagious form of disease. Pharyngoconjunctival fever,
associated with serotypes 3 and 8 also occurs in epidemic form
Fig. 4.1 Unilateral or asymmetrical lid swelling and conjunctival
inflammation is typical of early infection.
transmission by fomites, or neuronal spread in the case of latent
herpetic infection. Less commonly, viral eye disease may be part
of a generalized viral infection in which the eye is only one of
several organs involved (e.g. cytomegalovirus, rubella, human
immunodeficiency virus (HIV) infection). Where no specific
therapy exists for viral infection of the external eye symptomatic
treatment is usually all that is required until resolution takes
place. In cases where specific therapy exists, for example in
herpes simplex or varicella zoster virus infections, early accurate
diagnosis is essential so that treatment with an antiviral may be
started early enough to influence the course of the disease .
when, as its name suggests, it is associated with upper respiratory
tract infection. Sporadic disease has been associated with
adenovirus serotypes 1, 2, 4, 5, 11, 13, 14, 15, 20, 21, 23,24 and
29. Although the severity of adenovirus infections may vary
considerably certain clinical features are common to the majority
of cases.
Fig. 4.2 The early stages of adenovirus conjunctivitis are often
accompanied by a profuse watery discharge with marked
hyperaemia of the bulbar conjunctiva. This patient also has small
conjunctival haemorrhages which are sometimes present in the
acute phase in patients with severe disease.
 VIRAL INFECTIONS

A typical case of moderate severity presents with acute
bilateral but unequal, swelling and erythema of the eyelids
associated with conjunctival inflammation and a watery serous
discharge. There may be associated pre-auricular
lymphadenopathy, a history of contact with other similar cases
or a recent illness of the upper respiratory tract. Although the
conjunctival changes resolve over 7- 14 days, patients are often
left with ocular irritation and discomfort for several weeks.
This is due to tear film changes secondary to conjunctival
scarring or keratitis.

Fig. 4.3 During the first few days, the palpebral conjunctiva is hyperaemic with a fine papillary reaction. Small amounts of mucopurulent
discharge are often produced (right). Similar changes are visible over the upper tarsus (left) where, in severe cases, exudation of fibrin may
combine with mucus and lead to pseudo-membrane formation .

Fig. 4.4 During the first week, small follicles appear in the lower fornix and may later involve the tarsal surface. In the early stages, as in
this example, the follicles are greyish-white with slightly raised areas appearing in the subepithelial layers of the inflamed conjunctiva (top).
During the second week of the illness the follicles usually persist, although they become more discrete with resolution of the acute
inflammatory changes found elsewhere in the conjunctiva. Appearance of the same eye 3 days later (bottom). By the second or third week,
the conjunctival disease has usually resolved. The condition is self-limiting, although symptomatic relief may be obtained by the use of
topical lubricants.
INFECTIONS OF THE OUTER EYE

Fig. 4.5 In more severe infections, membranous conjunctivitis may result in sheet conjunctival scarring and symblepharon. This may
cause fornix shallowing and long-term discomfort.

Fig. 4.6 Adenoviral keratitis is seen with the more severe forms of the disease and is particularly associated with serotypes 8, 11 and 19 .
It is first visible as a fine punctate epithelial keratitis that appears during the first week of the disease.

subepithelial
infiltrates
··· · discret e
-'~"'----1 subepithel ial
diffuse epithelial opacity
punctate keratitis stained
with fluorescein

Fig. 4.7 In most cases the superficial keratitis resolves spontaneously but in more severe cases the epithelial lesions gradually coalesce
towards the end of the first week to form coarse spots that subsequently become associated with the appearance of subepithelial infiltrates
towards the end of the second week (left) . The epithelial lesions gradually resolve and as the inflammation disappears the edges of the
subepithelial infiltrate harden to produce discrete circular opacities (right) .

'
 VIRAL INFECTIONS

Fig. 4.8 The small circular subepithelial opacities, which are typically placed centrally in adenovirus infections, may persist for many
weeks, months or, rarely, years. This patient was photographed 2 years after the initial infection. Although the use of topical steroid
preparations results in the temporary disappearance of the corneal lesions, the value of such treatment is limited by the tendency for the
opacities to recur following withdrawal of steroids and the potential problems of long-term steroid treatment.

PICORNAVIRUS

This enterovirus causes epidemics of acute haemorrhagic
conjunctivitis in Africa and Asia but has not caused large
outbreaks in the Americas, Europe or Australia. Enterovirus type
70 has been identified as the cause. The incubation period is
about 1 day, much shorter than that of the adenovirus. The
features are acute lid swelling, painful haemorrhagic conjunctival
inflammation associated with subconjunctival haemorrhages, and
epithelial keratitis. The infection is highly contagious and spread
by secretions, body contact and fomites in densely populated
areas.

gross
gross
"--,"""'o:T"~~--j subconjunctiva l
subconj unctival
haemorrhage haemorrhage

Fig. 4.9 Both eyes are involved with an intense and severe haemorrhagic conjunctivitis. Corneal involvement is rare and recovery is
complete over 1- 2 weeks.
By courtesy of Dr M Viswalingam.
INFECTIONS OF THE OUTER EYE
HERPES SIMPLEX
Herpes simplex infection of the eye may be the result of either
primary or recurrent infection. Ocular disease, in common with
herpes labialis, is usually caused by herpes simplex virus (HSV)
type I, in contrast to genital infection which is associated with
HSV type II. Primary infection affects hitherto unexposed
individuals who have no immunity to the virus and is acquired
following inoculation from an infectious source. It
characteristically occurs in children and young adults up to the
age of 15 years as after that age serological evidence of exposure
to HSV is present in 50-90 per cent of individuals. In primary
infection the lesions occur on the skin around the
mucocutaneous junctions and are associated with regional
lymphadenopathy. In the nonimmunocompromised patient the
primary disease heals within 3 weeks although the virus then
persists in latent form. In the immunocompromised patient
generalized infection may occur requiring systemic antiviral
therapy. Recurrent infection in the eye may take the form of
blepharoconjunctivitis similar to that occurring in primary
disease although it usually runs a shorter time course. However,
corneal disease is more common with characteristic dendritic
ulceration occurring in the epithelium with deeper corneal
stromal keratitis or keratouveitis becoming more common with
successive recurrent attacks.
Primary herpes simplex infection normally induces a specific
antibody response with the production of IgM initially and later
raised IgG levels which persist. Intracellular virus is not
accessible to antibody and the role of the humoral response is
mainly in limiting the spread of the virus during viraemia and
promoting antibody-dependent cell-mediated cytotoxicity. There
is good evidence that cell-mediated immunity plays an important
role in combating HSV infection as protection against infection
can be transferred to immunosuppressed animals by T
lymphocytes but not by antibody and the disease is more severe
where there is suppressed cell-mediated immunity. Herpetic
disease may be more severe, and frequently bilateral, in patients
with atopy.
Fig. 4.10 Primary herpetic blepharoconjunctivitis begins as a
vesicular eruption with surrounding erythema on the skin of the
eyelids. After a few days the lesions become pustular, then crust
and ulcerate. Healing takes place during the second and third
week. A follicular conjunctivitis is also usually found.
'
 VIRALINFECTIONS 9

Fig. 4.11 Ulceration of the mucocutaneous junction of the lid margin is common. In recurrent blepharoconjunctivitis due to herpes
simplex lid margin ulcers, which will stain with fluorescein, may occur with conjunctivitis in the absence of skin lesions and may be the
only evidence of specific herpes simplex infection.

ulcerated ~"'----~--------~....,-TrT7!r:-l

conjunctiva

co nj unctiva l crypts

Fig. 4.12 Conjunctivitis is often present with the primary disease when it is invariably associated with a tender, enlarged, pre-auricular
lymph node. It is frequently accompanied by purulent discharge and the lower fornix and tarsus show a mixed papillary and follicular
reaction indistinguishable from other types of viral conjunctivitis. The upper tarsus shows small areas of conjunctival ulceration near the lid
margin that are easily overlooked in the presence of marked hyperaemia . The conjunctivitis responds to treatment with a topical antiviral
agent.
94 INFECTIONS OF THE OUTER EYE

Fig. 4.13 Herpes simplex keratitis is usually unilateral. Small single or multiple dendritic ulcers are seen only rarely in the primary
disease where, if keratitis is present, it is more commonly a punctate epithelial keratitis. In this example multiple small dendrites stained
with Bengal Rose are present over a large area of the corneal surface. Following a primary infection of the eye, herpes simplex virus
remains latent within the trigeminal ganglion and is transmitted to the eye by the fifth nerve producing recurrent disease, sometimes in
association with stress or systemic illness.

Fig. 4.14 A dendritic ulcer, the hallmark of recurrent corneal

herpetic epithelial keratitis. Fluorescein stains the area of epithelial
cell loss; disease is limited to the epithelium. Dendritic ulcers heal
in about 7 days with a topical antiviral agent.

··.~~·
~I

~. ' · ' ·' .

_.../ ·''
..

: '-/

Fig. 4.15 'Amoeboid' or 'geographical' herpetic ulceration almos1

invariably results from the inadvertent use of topical steroids either
for keratoconjunctivitis caused by herpes simplex or for
unrecognized epithelial ulceration. Persistent treatment with
steroids will lead to corneal destruction and perforation.
 VIRALINFECTIONS 9

area of stromal
-~-+----'---1 infiltrate and
oedema

Fig. 4.16 Chronic active stromal herpes simplex keratitis involves reactivation of viral replication in the stroma with an associated
immune response. This patient has an area of ulceration surrounded by stromal oedema and infiltrate in an old herpetic scar. KP may be
seen on the corneal endothelium in the involved area. There is superficial corneal vascularization. Topical steroids with antiviral cover are
indicated to suppress the inflammatory reaction and minimize subsequent scarring.

Fig. 4.17 Disciform keratitis can arise with or without a history

of previous corneal ulceration and presents as an area of stromal
oedema associated with uveitis. These photographs shows an area
of diffuse corneal stromal opacification with multiple underlying
keratic precipitates centrally, indicating an active keratitis.
Treatment with a combination of topical steroid and antiviral will
suppress inflammation and subsequent vascularization. However,
this treatment may have to be continued for many months to
prevent rebound inflammation. Residual stromal scarring is usual.
Patients with frequent recurrences of disease benefit from long-
term oral antiviral treatment, which reduces the number and
severity of relapses.

Fig. 4.18 A Wessley ring is another example of an immunological phenomenon occurring in the corneal stroma associated with herpes
simplex keratitis. This is formed when soluble antigen diffuses away from the site of infection through the corneal stroma to form a
precipitation line where it is neutralized by antibody.

•
 INFECTIONS OF THE OUTER EYE

Fig. 4.19 This figure shows an end-stage chronic herpes simplex keratitis with vascularization and lipid deposition in an old stromal scar.
Lipid keratopathy may also be seen in any condition that has resulted in the presence of a vascularized scar. A well pronounced arcus senilis
is also present.

epithelium ~:;:;:;:::~:.~..:::==::::;;FS.::<;:....:~"':,;csz. . . thinned

Bowman's layer
--~~-:·,t.~· ~-,~~~-i\~
.. -. •. ": .·-, ····

chron ic
'~ '·
• •~ ~-- ., ,, -. I.
-~- . . ~:~-:a;~~~; ~.~: ~ infl ammatory cells

Fig. 4.20 The histological features of herpes simplex stromal keratitis show an intact corneal epithelium with destruction of parts of
Bowman's layer beneath which there are collections of lymphocytes and plasma cells. Vascularization of the corneal stroma is also evident
with loss of the normal pattern of corneal lamellae.

HERPES ZOSTER

Herpes zoster ophthalmicus results from the activation of latent
varicella zoster virus in the trigeminal ganglion with neuronal
spread of virus through the first (ophthalmic) division of the
nerve. The resulting vesicular eruption follows the distribution
of the affected dermatome and may be preceded by a few days
of neuralgic pain in the same area. A wide spectrum of ocular
involvement may occur, including conjunctivitis, keratitis,
corneal anaesthesia, iritis (see Ch. 10), secondary glaucoma or
optic neuritis. Possible mechanisms of tissue damage include
direct viral invasion, vasculitis and neuritis. Isolated ocular
motor nerve palsies may also occur as a result of contiguous
viral spread within the cavernous sinus. Systemic treatment with
an antiviral drug early in the course of the disease shortens the
duration and extent of the rash and reduces long-term ocular
complications and postherpetic neuralgia, which can be
disabling in some patients. Herpes zoster infections usually
occur in otherwise healthy people but may be precipitated by
debility or immunosuppression from other disease; they are also
associated with HIV infection and acute retinal necrosis (see
Ch. 10).

'
 VIRAL INFECTIONS 97

Fig. 4.22 Involvement of the nasociliary branch of the

ophthalmic division of the trigeminal nerve is often associated with
ocular complications from herpes zoster. This patient illustrates the
healing phase of the rash during the second week when crusts have
started to form and the erythema is subsiding.

Fig. 4.21 This is an example of a zoster rash in the early stages

with erythema, oedema of the lower lid, and vesicle and pustule
formation following the distribution of the second (maxillary)
division of the trigeminal nerve. Ocular involvement is much less
common in this instance.

Fig. 4.23 The late stigmata of zoster infection include marked

dermal atrophy leading to thinning and depigmentation of the skin,
pseudodentrites
sometimes associated with more extensive tissue destruction from stained with
arteritis and inflammation. This patient has a lateral tarsorrhaphy Bengal Rose
to protect the right cornea. Such cutaneous damage has become
rare with the introduction of antiviral treatment.

Fig. 4.24 Conjunctivitis and keratitis are features of ocular

involvement during the early stages of the disease. Corneal
'pseudo-dendrites' from mucus deposition may form but these can
be distinguished from the dendrites of herpes simplex infection by
their elevated appearance, peripheral location, poor staining with
fluorescein compared with Bengal Rose and their ability to be
wiped easily from the corneal surface.

•
Fig. 4.25 Disciform keratitis is a common feature of corneal
disease in herpes zoster. It usually appears about 2 weeks after
onset of the rash, with blurring and photophobia. There is stromal
oedema with KP on the endothelium and often a concurrent iritis.
The cornea has reduced sensitivity. The changes are identical to
those of herpes simplex stromal keratitis.
Fig. 4.26 Corneal anaesthesia or hypoaesthesia is a frequent
complication of herpes zoster ophthalmicus. When this is
combined with defective lid function (see Fig. 4.23), exposure may
result in drying with ulceration of the corneal epithelium. In this
example a small perforation has appeared in the base of an ulcer in
the inferior cornea.

sectorial atrophy

Fig. 4.27 Approximately 50 per cent of patients with ocular involvement develop iritis and this is frequently accompanied by vasculitis of
the iris. Secondary glaucoma is common. The uveitis starts during the third or fourth week of the illness and usually requires treatment
with topical steroids for many months. Sector iris atrophy from vasculitis of the radial iris arterioles is characteristic in such patients.
Examination of the pupil on direct illumination may show loss of the pigmented border in a sector that reacts poorly to light, producing a
characteristic spiralling of the pupil on constriction to light (see Ch. 10). The loss of the iris pigment epithelium can be seen more
dramatically on retroillumination.

•
 VIRAL INFECTIONS

MOLLUSCUM CONTAGJOSUM

This is a pox virus that is transmitted by close bodily contact. No the lesions are commonly seen on the face. Ocular involvement
animal host is recognized. Incubation is usually 2-7 weeks and occurs when a lesion is present at or near the lid margin.

Fig. 4.28 Molluscum contagiosum produces characteristic raised

skin lesions with umbilicated centres. The lesions may be either
single or, as in this case, multiple.

Fig. 4.29 If a molluscum lesion occurs on the lid margin virus particles may be shed into the lower conjunctival sac where they may
produce a secondary follicular conjunctivitis. This is thought to be due to an immune reaction without direct conjunctival invasion by the
organisms. The conjunctivitis thus produced is readily cured by removing the offending lid lesion.

CHLAMYDIAL INFECTIONS
Chlamydiae form a unique group of small bacteria comprising
a single order and one genus, the Chlamydiae, with two
species, Chlamydia trachomatis and Chlamydia pneumoniae, that
cause human disease . Because they are obligatory intracellular
parasites they were in the past considered to be viruses but
have since been reclassified as bacteria as they are larger than
viruses, possess both DNA and RNA, have a more complex
structure with a cell wall, and are capable of division by binary
fission. They are also sensitive to some antibiotics. Different
subgroups of C. trachomatis produce different diseases, such as
neonatal pneumonitis, lymphogranuloma venereum and
~-~:;;;~~;:;:~------l thickened epidermi s
conta inin g eosinophilic
inclusion bodies
Fig. 4.30 Histological examination of an excised lesion shows
lobules of thickened epidermis with a central pit. The epidermis
contains large numbers of eosinophilic inclusion bodies, which are
discharged centrally on to the umbilicated surface.
oculogenital infections, in humans. Serotypes A, B, Ba and C
are associated with trachoma, whereas serotypes D - K are
associated with genitally transmitted disease causing
conjunctivitis.
Chlamydiae are obligatory intracellular parasites. The
diagnosis of chlamydia! infection is now made either by the
polymerase chain reaction (PCR) for chlamydia! DNA or by
enzyme immunoassay on conjunctival discharge; previously it
was made by culture of conjunctival swabs in cell culture or the
demonstration of the characteristic intracytoplasmic inclusion
bodies in the conjunctival scrapings.
double eversion
of eyelid
Fig. 4.31 The conjunctival fornices show a pronounced follicular
reaction associated with hyperaemia and some infiltration of the
surrounding conjunctiva. Follicles in the upper fornix (left) can be
inspected only by double everting the upper lid. In the lower fornix
(right) individual large follicles have begun to coalesce to produce
ridges of lymphoid material.
•
 CHLAMYDIALINFECTION

INCLUSION BODY CONJUNCTIVITIS

This is so called because of the inclusion bodies seen watering and sticky eye accompanied by a slight ptosis. Keratitis
intracellularly on conjunctival smears. This form of conjunctivitis is uncommon . There is associated pre-auricular lymph node
usually has a gradual onset over a period of several weeks. It is enlargement. It is a sexually transmitted disease acquired from an
usually unilateral and the patient presents with an inflamed, infected partner following direct or indirect oculogenital contact .

..,...,.~-----1 fine papillae

Fig. 4.32 The follicular response later spreads on to the tarsal conjunctiva, where the follicles tend to be smaller and are associated with
other inflammatory signs including a papillary reaction.

Fig. 4.33 Superficial keratitis may develop in the form of small

greyish-white epithelial and subepithelial infiltrates 2- 3 weeks after
epithe li al keratitis
the onset of conjunctivitis. These infiltrates may be distinguished
from those seen in adenovirus by their tendency towards a
peripheral corneal distribution and their association with early
pannus formation. They may persist for several months.
 cervical
opening

Fig. 4.34 Inclusion body conjunctivitis is transmitted sexually or during birth and is associated with cervicitis in women and urethritis in
men; proctitis may also be present and consequently systemic treatment is usually indicated. This woman has well developed follicles on the
cervix, characteristic of chlamydia! infection. As Chlamydiae are associated with pelvic inflammatory disease and infertility all patients
should be screened for evidence of chlamydia! genital infection and other coincidental sexually transmitted diseases.

Fig. 4 .3 5 In the newborn infant infection may be acquired in the

birth canal during delivery and Chlamydiae are an important cause
of ophthalmia neonatorum. The incubation period is usually 5- 14
days but varies from 1 to 40 days. The clinical appearance of the
inflamed conjunctiva differs from the adult form of the disease as
the infant's immature immune system does not allow follicle
formation. The palpebral conjunctiva are hyperaemic and
oedematous with a papillary reaction and are readily everted by
gentle pressure on the lids from the examiner's fingers. In this
example mucopurulent exudate is present. It is important to
visualize the cornea to exclude ulceration although this is more
common with bacterial infections. Babies may develop systemic
infection and should be treated with systemic antibiotics.

TRACHOMA

Trachoma is one of the world's leading causes of blindness. It has
been estimated that about 500 million people have been affected
by this disease of whom 100 million suffer some visual
impairment and at least two million are totally blind. The disease
results from repeated infection by Chlamydia trachomatis of
serotypes A-C which may be made worse by superimposed
bacterial infection. The disease has long been recognized as being
hyperendemic in North Africa, the Middle East, the Indian
subcontinent, the Far East and Australia but is also found in
poorer parts of Central and Latin America. Transmission takes
place from eye to eye by flies, fomites and body contact, and the
maintenance and spread of the infection in a population are
facilitated by overcrowding, poor conditions of hygiene and,
especially, shortage of water for face washing. The blinding
complications are caused by corneal opacity from conjunctival
scarring and trichiasis with intercurrent bacterial infection.
Treatment of an infected individual consists of either oral
antibiotics (sulfonamides, erythromycin or tetracycline) for 3
weeks or topical tetracycline ointment for 6 weeks. In
communities with hyperendemic trachoma mass treatment with
antibiotics may be effective in reducing the pool of infection but
preventive measures including the provision of a plentiful water
supply, improved sanitation and health education offer the only
certain way of tontrolling the disease. Surgical management of
trichiasis has a ~~gnificant effect on reducing blindness.
The classical description of trachoma has four stages of
disease progression: stage 1, small follicles on the conjunctiva;
stage 2, mature follicles with diffuse infiltration and papillary

hypertrophy; stage 3, conjunctival scarring and active
inflammation; stage 4, inactive infection and scar tissue.
Although these broad categories of disease may be recognized in
a population with hyperendemic trachoma, the classification is of
limited value in determining the prognosis in an individual
patient as it takes no account of the cyclical changes brought
about by reinfection, the severity of the disease or the degree of
visual damage. The World Health Organization has introduced a
simplified classification for primary eye care, which can be
hyperaemia
Fig. 4.37 Early trachoma with rollicles and diffuse inflammatory changes on the tarsal plate and no scarring (left), resolving follicles, mild
inflammatory changes and early scarring (right).
I
By courtesy of Mrs D Mabey.
I
CHLAMYDIAL INFECTIONS 10l
performed with a hand torch and Ioupe in the field and can be
expanded by grading the severity. This consists of trachoma
follicles (TF; five or more follicles on the central upper tarsus),
trachomatous inflammation (TI; diffuse inflammation of the
upper tarsal conjunctiva that obscures more than 50 per cent of
the normal tarsal vessels), trachomatous scarring (TS), trichiasis
or entropion (TT; deviated lashes touching the cornea) and
corneal opacity (CO).
Fig. 4.36 Children are the major reservoir of disease, and eye-to-
eye contact via flies is a major factor in disease transmission.
By courtesy of Mrs D Mabey.
04 INFECTIONS OF THE OUTER EYE

Fig. 4.38 Resolving follicles, papillary changes and scarring (top). Extensive scarring with residual inflammation (bottom). Dense scar
tissue near the upper lid margin may contract leading to lid shortening and trichiasis (see also Figs 3.18 and 3.19) .
By courtesy of Mrs D Mabey. ~

active pannus
w ith dilated
vesse ls
limbal follicles

stromal
infiltrate

Fig. 4.39 Active corneal disease with limbal follicles and superficial pannus.
 CHLAMYDIAL INFECTIONS 105

Herbert's pits

Fig. 4.40 Severe corneal scarring with inactive pannus (superficial downgrowth of vessels and scarring without infiltration) (left) . Shallow
depressions, known as Herbert's pits, can be seen in another eye (right). These represent the site of earlier limbal follicles that have
involuted leaving residual corneal stromal thinning.
By courtesy of Mr M G Falcon.

loss of fornix

Fig. 4.41 The complications of severe trachoma result from the contraction of conjunctival deep scar tissue leading to cicatricial
entropion, trichiasis and lid shortening (which may in turn lead to further corneal damage) in association with dry eye, also as a result of
conjunctival disease . This leads to corneal scarring, vascularization and epithelialization exacerbated by secondary bacterial infection and
mechanical trauma from the lid changes.
By courtesy of Mr M G Falcon.
INFECTIONS OF THE OUTER EYE

BACTERIAL INFECTIONS

Bacterial infections of the external eye usually respond rapidly to

treatment with antibiotics, although under certain circumstances
serious complications may follow. Superficial infections of the
lids and conjunctiva may be treated with topical broad-spectrum
antibiotic preparations, whereas deeper infections such as
dacryocystitis and orbital cellulitis require systemic treatment.
The most serious bacterial infections are those involving the
cornea; these require urgent investigation and intensive
treatment if loss of vision through corneal perforation, scarring
or endophthalmitis is to be avoided (see Ch. 6).

Fig. 4.42 Acute bacterial

infections of the eyelid
usually take the form of a stye
in which a lash follicle
becomes infected or acute
chalazion in which one of the
meibomian glands of the
eyelid is involved.

lash follicles

Fig. 4.43 A stye is a small localized abscess visible on the lid

margin around the root of an eyelash. Resolution occurs
spontaneously following removal of the eyelash and no further
treatment is indicated.

Fig. 4.44 Acute chalazion is an infection of a meibomian gland in which localized abscess formation takes place within the tarsal plate.
The infection may be treated with heat and antibiotic ointments, but resolution tends to be slow and a painless swelling may persist for
several weeks or months owing to the formation of a granuloma (chalazion, meibomian cyst). At this stage surgical incision and curettage
can be performed to remove the lesion (see Ch. 2).
 BACTERIAL INFECTIONS 107

CHRONIC BLEPHARITIS

Chronic blepharitis is a common bilateral condition. It can be
associated with seborrheic dermatitis, rosacea, discoid lupus or
atopic dermatitis although most patients have no other disease.
Blepharitis itself can frequently be asymptomatic but its
associated conjunctivitis or keratoconjunctivitis result in
significant morbidity. Patients complain of redness oflid margins,
soreness, irritation and burning with crusting of the lashes in the
mornings. It can be classified clinically into two broad groups
according to whether there is mainly anterior (skin and lashes) or
posterior (meibomian) involvement. Hypersensitivity to
staphylococcal antigens appears to play a role in the pathogenesis
of the conjunctival and corneal complications.

red swo llen

lid margin

1/ <

Fig. 4.45 Anterior blepharitis is characterized by the presence of crusts and scales on the lid margins which may be erythematous and
slightly swollen, and chronic staphylococcal infection. The eyelashes are irregular and fewer in number than normal. Conjunctival
inflammation is unusual. Most cases respond to simple lid margin cleansing and antibiotic ointment applied to the lid margins .

mild scarring
di lated blood vesse ls hyperaemia
along lid margin
tarsal
hyperaemia

Fig. 4.46 Posterior blepharitis is characterized by meibomian gland dysfunction. The lid margin is red and thickened and the meibomian
gland orifices are filled with an oily or thickened secretion that can be expressed by pressing on the lid margin. Signs of chronic
conjunctival inflammation are usually present. The condition may be associated with changes in meibomian lipids resulting in stagnation
and occlusion of the gland openings. An increased staphylococcal population may generate local hypersensitivity reactions which may be
particularly symptomatic in some individuals. Lid toilet with bicarbonate solution or water with baby shampoo helps to remove oily
secretions from the lid and lashes. More severe cases can be treated with long-term systemic low-dose tetracycline and, where necessary,
dilute topical steroid may be used with caution to control the hypersensitivity reaction.
 Fig. 4.47 Marginal keratitis appears in association with chronic
blepharitis when discrete yellowish-white infiltrates appear in the
area of peripheral periphery of the cornea, usually singularly but occasionally with
corneal oedema involvement in more than one quadrant. Localized injection of the
and infi ltrate conjunctiva is visible adjacent to the area of keratitis. The condition
is the result of a localized staphylococcal hypersensitivity reaction
(although identical changes can occasionally be seen with herpes
simplex virus) and responds well to topical steroid drops.

ROSACEA

Fig. 4.48 Excessive meibomian secretion may also

be a feature of acne rosacea. This photograph shows
the characteristic facial appearance of the condition
(left) together with the rhinophyma associated with
sebaceous hypertrophy (right). Note the superficial
dilated blood vessels.
 BACTERIAL INFECTIONS

r?-J:::::~SE¢,;.L:7l:-----'7't-J stromal thinning

.llif:y--~<::::__.::_:::::::::1 su perficia I
'---~--""------"---"'"-'--~-'--""--L---~ vascu Ia rization

stromal infi ltrate

Fig. 4.49 A mild case of acne rosacea-associated keratoconjunctivitis shows fine superficial neovascularization of the limbus extending on
to the cornea (top). In a more severe case there is blepharoconjunctivitis, m arked corneal vascularization and scarring (middle). With active
disease the vessels are dilated and there is often a cellular infiltrate at their tips. Vascularization may be associated with thinning and, rarely,
perforation of the peripheral cornea (b ottom) .
 IONS OF THE OUTER EYE
BACTERIAL CONJUNCTIVITIS
Fig. 4.50 Bacterial conjunctivitis is characterized by its acute
onset, profuse thick purulent discharge and rapid response to
topical antibiotic therapy. Diagnosis depends on the demonstration
of causative organisms by standard bacteriological techniques.
Important causes include Staphylococcus, Pneumococcus, Moraxella
and Haemophilus bacteria.
LEPROSY
It has been only in recent years that leprosy has been recognized
as a major cause of world blindness. It affects around 15 million
people, of whom one million are blind. The ocular sequelae vary
widely between racial groups and geographical location, and are
related to the predominance of lepromatous leprosy, temperate
climate and lack of health care. Damage to the eye occurs from
Fig. 4.52 The zygomatic branch of the seventh nerve is often
selectively involved because it is relatively superficial, cooler and
therefore predisposed to bacterial invasion. Partial seventh nerve
palsies are common, leading to gross corneal exposure.
By courtesy of Mr T J ffytche.
Fig. 4.51 Ophthalmia neonatorum can be due to Chlamydiae
(see Fig. 4.35), but is more commonly a result of bacterial
infection acquired during birth or from cross-infection in the
neonatal period. Staphylococcal infections are the most common
cause although gonococcal infection used to be a severe problem
producing a florid purulent conjunctivitis that led to blindness
from corneal involvement. In preantibiotic days, babies were
treated prophylactically with silver nitrate drops postdelivery to
prevent this complication. It is essential to visualize the cornea in
any baby with conjunctivitis to exclude corneal ulceration.
direct invasion of the eye by the bacilli in lepromatous leprosy,
and from loss of corneal sensation and defective lid closure from
a seventh nerve palsy compounded by facial and hand
deformities. Vision is lost from corneal exposure and infection, or
from chronic iritis, miosis and cataract.
Fig. 4.53 The anterior chamber has a lower temperature than
body temperature and the anterior segment is vulnerable to direct
invasion by bacilli. Corneal anaesthesia results from involvement of
the corneal nerves and is exacerbated by the problems of exposure.
A low-grade chronic iritis is common; it destroys iris tissue and
may cause cataract. Sympathetic nerves are selectively affected in
the iris as they are small and nonmyelinated and this produces
characteristic severe chronic miosis that enhances the effects of
lens opacities.
By courtesy of Mr T J ffytche.
 PARASITIC DISEASE AND INFESTATIONS

Fig. 4.54 The physical deformities of leprosy with loss of the nose and fingers add to the
therapeutic problems.
By courtesy of Mr T J ffytche.

ANTHRAX

Anthrax is seen in developing countries; it results from close forms spores. The spores will survive for years and can transmit
contact with infected animals or rarely in developed countries the disease through infected material that has originated
from contact with infected animal products such as bones or thousands of miles away.
hides. The disease is caused by a Gram-positive rod that readily

Fig. 4.55 Cutaneous lesions are characteristic. This Libyan

woman has the typical coal-black eschar of resolving anthrax
infection on the right upper lid. The disease starts as a pimple with
oedema and no pus surrounded by purplish vesicles. The eschar
forms rapidly in a few days and eventually sloughs, with scarring of
the lid and corneal exposure.
By courtesy of Mr ]Winstanley.

PARASITIC DISEASE AND INFESTATIONS

PEDICULOSIS

Lice on the eyebrows or eyelashes are an unusual cause of body shape. The pubic hair must be treated as well as the lashes.
blepharoconjunctivitis. They are pubic lice rather than head lice, Adult lice live for about 1 month; transmission is through close
as the wider spacing of the lashes is more suitable to their broader body contact or clothing.
112 INFECTIONS OF THE OUTER EYE

Fig. 4.56 'Nits' are the empty egg cases on the eyelashes.

Fig. 4.57 Lice are almost transparent unless they contain blood,
and are easily missed on examination.

hair
nit

Fig. 4.58 A pubic louse clinging to a pubic hair. An egg case is

attached.

LOA LOA

This is endemic in west and central Africa. Microfilariae are subcutaneous tissues and may sometimes be seen under the
spread from human to human by bites from the chrysops conjunctiva.
horsefly. The worms mature over a year and may live for up to Transient allergic lumps known as Calabar swellings occur on
15 years. They are up to 7 em long; they migrate through the the body. Patients may have an eosinophilia.

Fig. 4.60 This worm was seen in the patient's conjunctiva by his girlfriend 2 days previously. It then migrated to the subcutaneous tissue
of the upper eyelid. Surgical removal can be effected by a skin incision under local anaesthesia.
ONCHOCERCIASIS (RIVER BLINDNESS)
This disease is caused by the microfilaria Onchocerca volvulus and
is endemic in central Africa and in central and southern America,
where it was probably introduced through slavery. The vector is
the blackfly species Simulium which feeds in rapidly flowing
water. The adult transmits larva to the human host. The larvae
spread subcutaneously and mature to adult worms forming
rubbery nodules that contain both male and female worms. The
worms can be up to 50 em in length and may live for 10 years.
The female produces millions of microfilaria which migrate
subcutaneously throughout the body. These can survive for up to
18 months to reinfect the blackfly and repeat the cycle. About
PARASITIC DISEASE AND INFESTATIONS
worm
Fig. 4.59 If the worm is seen under the conjunctiva it should be
paralysed by topical anaesthesia as they move quite rapidly and can
escape easily.
By courtesy of Mr T J ffytche.
8- 10 million people are infected; one million of these are blind.
In highly infected areas 100 per cent of the population are
affected and 50 per cent are blind.
The effects of the infestation are confined to the skin and the
eye and are produced by the low-grade inflammatory reaction
that is incited by dying microfilaria. Vision is lost from sclerosing
keratitis, chronic anterior uveitis, chorioretinitis or optic neuritis.
Visual loss may be exacerbated by treatment that kills the
microfilaria thus producing further inflammation. Ivermectin,
which prevents the microfilaria from leaving the adult female is
the principal microfilaricidal agent.
Fig. 4.61 The presence of dead microfilaria produces an
intensively itchy rash, particularly on the lower body. There is
hyperpigmentation and atrophy of the skin which heals badly.
Trophic ulcers may develop.
14 INFECTIONS OF THE OUTER EYE

Fig. 4.62 Adult worms form nodules throughout the body, but
particularly subcutaneously over bony prominences. If the nodules
are on the head they are particularly dangerous, as the microfilaria
easily spread to the eye. Nodules can be excised surgically.

live microfiliariae
in cornea

Fig. 4.63 Microfilaria can be seen in the cornea, aqueous and vitreous as mobile, small, slender structures about 0.3 mm in length. They
enter the eye from the surrounding subcutaneous tissue which is why it is particularly important to remove adult worm nodules from the
head.

snowflake opacities

Fig. 4.64 Dead microfilaria produce fluffy 'snowflake' opacities in the anterior corneal stroma.
By courtesy of Mr I Murdoch.
------------~-------

PARASITIC DISEASE AND INFESTATIONS 11

Fig. 4.65 More advanced cases show a blinding sclerosing keratitis with pigmentary migration on to the cornea.
By courtesy of Mr I Murdoch.

diffuse pigment
epithelial changes optic atrophy attenuated arteries
focal pigment
epithelial atrophy
optic atrophy
chorioretinal
atrophy
L __ _~~~~--~

Fig. 4.66 Chorioretinal atrophy and optic neuritis are produced
by a low-grade chorioretinitis. The early changes are seen temporal
to the macula as atrophy of the retinal pigment epithelium. They
probably arise from invasion of the choroid along the posterior
ciliary arteries by microfilaria which are frequently produced in
nodules on the temples.
By courtesy of Professor A Bird.
Fig. 4.67 More advanced changes are seen in this eye. The
macula is often spared until late in the disease. Optic nerve disease
and visual field loss may occur in the absence of retinal disease.
Diethylcarbamazine (DEC) destroys the microfilaria but may
precipitate further visual loss from the reaction to dead microfilaria
in the optic nerve and retina.
By courtesy of Mr I Murdoch.
Allergic Eye Diseases,
Episcleritis and Scleritis
Frank Larkin, Paul Hunter

Allergic Eye Disease

Oculocutaneous Cicatricial Disorders
Ocular Surface Disorders
Diseases of the Sclera and Episclera
118 AllERGIC EYE DISEASES, EPISClERITIS AND SCLERITIS
ALLERGIC EYE DISEASE
Allergic eye disease in its various forms is a common cause of
ocular morbidity in both primary care and specialist practice.
The external eye is under constant immunological challenge
from a wide variety of substances; this may lead to the
development of one of many conditions that can be loosely
grouped as 'allergic eye disease'. The chief factors determining
the outcome of such challenges are the severity and duration of
the antigenic load and the immunological status of the
individual. Local or systemic immune mechanisms may be
involved to produce immediate hypersensitivity, complement-
mediated or delayed hypersensitivity reactions. The spectrum of
allergic conjunctivitis (Table 5.1) ranges from mild self-limiting
"Se'a'S\\ll'l.a\ conjunctivitis to atopic keratoconjunctivis in which
vision is threatened by corneal vascularization, herpetic epithelial
Table 5.1 Differential diagnosis of allergic conjunctivitis
Without keratopathy With keratopathy
Seasonal allergic (hay fever) conjunctivitis Vernal keratoconjunctivitis
Perenn ial allergic conjunctivitis Atopic keratoconjuncti vitis
Atopic blepharoconjunctivitis
Giant papillary conjunctivitis
IMMEDIATE HYPERSENSITIVITY REACTIONS
Fig. 5.1 Acute periorbital oedema is a common manifestation of
immediate hypersensitivity and appears within minutes of
exposure. It may follow the systemic administration of antigen in a
sensitized individual such as the ingestion of foods or drugs. The
reaction is frequently associated with high titres of circulating IgE
antibody, being mediated by the release of histamine and other
pharmacologically active substances from mast cells in the skin and
mucosal tissues. It usually produces symmetrical bilateral lid
oedema which may also be accompanied by conjunctival chemosis
and urticarial skin rashes. The onset is rapid but the signs usually
improve within a few hours. Acute unilateral signs may result from
local inoculation and histamine release in the skin, as in this
patient where the reaction followed an insect bite.
infection and the long-term complications of topical
corticosteroid therapy. Although patients complain of red, sore
and discharging eyes, itchiness is the characteristic symptom of
allergic eye disease. Patients also have an increased risk of
keratoconus and atopic cataract. Increased levels of IgE and
eosinophils are found in the conjunctiva and a wide range of
inflammatory mediators have been shown to be involved in the
pathogenesis.
Treatment involves identification and avoidance of the
offending antigen and the administration of antihistamines, mast
cell stabilizers or steroids. Mild disease responds to topical
antihistamine or mast cell-stabilizing agents alone but corneal
involvement requires topical steroids, often over prolonged
periods with surveillance for steroid side-effects.
Fig. 5.2 Acute conjunctival chemosis may occur in the absence
of lid swelling as an immediate hypersensitivity response to local
inoculation of antigenic substances (frequently pollens) directly on
to the conjunctiva of a sensitized individual. The level of response
depends on the degree of previous sensitization and the dose of
antigen. In this patient, although both conjunctiva are chemotic
and slightly hyperaemic, the signs are more pronounced in the left
eye.
 ALLERGIC EYE DISEASE 11!

Fig. 5.3 Phlyctens are inflammatory nodules usually seen on the

nasal limbus with an associated hyperaemia. They are bilateral and
are usually seen in children and young adults. Phlyctens represent
a lymphocyte cell-mediated response in a previously sensitized
individual. They are associated with a variety of antigens;
staphlococci are now the commonest cause, but in the past the
main cause was tuberculosis.

ALLERGIC CONJUNCTIVITIS

Fig. 5.4 Atopic blepharoconjunctivitis is typified by thickening of eyelid and periocular skin. Conjunctival inflammation is moderate and
keratopathy is absent.

corneal
vascularization

stringy mucus

tarsal scarring

Fig. 5.5 Atopic keratoconjunctivitis is uncommon and is usually seen in young men with atopic dermatitis and a history of childhood
eczema. The ocular changes are seen in early adult life; they are bilateral, symmetrical and persistent for many years. The conjunctival
changes carry a significant risk of sight-threatening complications which include corneal vascularization, herpes simplex viral keratitis and
steroid-induced glaucoma. Cicatrizing conjunctivitis and fornix shortening results from progressive subepithelial scarring.

/
 --------- ------- ---·--·~------

120 ALLERGIC EYE DISEASES, EPISCLERITIS AND SCLERITIS

VERNAL KERATOCONJUNCTIVITIS

Vernal keratoconjunctivitis (VKC) is an ocular manifestation of
atopy. There is frequently a history of eczema, hayfever and
asthma which characteristically starts early in life. The disease is
bilateral and chronic with seasonal exacerbations and remissions
and predominates in young males. It is common in the hot dry
climate of the Middle East. Patients are usually allergic to
multiple antigens and have seasonal exacerbations, often
improving around puberty. Itching and ocular discomfort with
mucoid discharge are the predominant symptoms.
The aim of treatment during acute exacerbations is to control
symptoms by reducing conjunctival inflammation. In less severe
forms of the disease single agents may be successful in controlling
the disease but in severe cases intensive topical steroids are
usually needed. Mucolytic preparations such as acetylcysteine
drops can be useful in removing excess mucus. It is important to
reduce topical steroids as soon as possible to avoid ocular
complications such as glaucoma and this may be facilitated by
the additional use of a mast cell-stabilizing drop for its steroid-
sparing effect.

Fig. 5.6 This boy, who suffers from VKC, shows a typical
eczematous rash on his forehead and cheeks. There is an associated
slight bilateral ptosis reflecting the chronic inflammation on the
upper tarsal conjunctiva.

giant papillae

mucus

Fig. 5.7 Giant papillae on the upper tarsus, typically described as having a 'cobblestone' appearance, are the hallmark ofVKC. Although
these papillae persist during quiescent phases they become swollen and infiltrated by oedema and inflammatory cells with abundant
abnormal mucus both on the surface and in the crevices between the papillae when the disease becomes active, as in this example.

(
... ALLERGIC EYE DISEASE

flat quiescent
papillae

Fig. 5.8 This eye shows less conjunctival swelling and mucus
discharge, indicating inactive VKC.

tubules and cysts

Fig. 5.9 A histological section ofVKC shows typical papillae with epithelial downgrowth to form tubules and cysts. The papillae have a
loose stroma in which inflammatory cells are seen. Eosinophils and basophils are present in large numbers during the active phase of the
disease.

Trantas' dot

Fig. 5.10 Limbal follicles may occur in VKC and are seen more commonly in black patients in the absence of marked tarsal papillae. This
is sometimes known as the 'limbal' form of the disease. These limballesions are heavily infiltrated with inflammatory cells and appear as
greyish, gelatinous swellings, especially around the superior limbus. The blood vessels are not unduly prominent and no mucus is visible.

(
\
;;cecnoac c I L OIJLAJL3, EFI5CLEKI1 15 AND SCLERIIIS

<:1) p··· .··· :)J\11 /r ·

r---
----,;1,.-,\ ,~>'
Tranta's dot 1-- -
0 0
~ '" /

limbal pall isades

,-J~.. · ·····.~~~g~·· of Vogt
"" \

Fig. 5.11 Trantas' dots are a feature ofVKC. They are small, white, elevated, epithelial lesions seen on the limballesions at the superior
limbus and contain eosinophils. In this example they are associated with a greyish corneal infiltrate.
By courtesy of Professor R J Buckley.

Fig. 5.12 This patient illustrates the early corneal changes seen
in vernal disease. There is a fine punctate epithelial keratopathy
consisting of fine grey dots which has become confluent in some
areas. Eosinophilic major basic protein from disrupted eosinophils
is cytotoxic and thought to play a major role in vernal keratopathy.
By courtesy of Professor R J Buckley.

Fig. 5.13 A vernal ulcer characteristically develops in the upper half of the cornea during active phases of tarsal disease and is shown
here stained with fluorescein. The edge of the ulcer is surrounded by whitish, heaped-up epithelium. The base is composed of abnormal
mucus that is deposited with fibrin and other serum constituents as a grey plaque. When established, this plaque prevents healing from
occurring. An area of superficial corneal infiltration can be seen nearer the limbus on the nasal side of the cornea.
By courtesy of Professor R J Buckley.
 ALLERGIC EYE DISEASE 1

....;;;\,--'-~-~.., 1 dry surface

of plaque

conjunctival rolled
hyperaem ia -..A.~;..J.._---"'?'-<::'1 epitheliaI edge

Fig. 5.14 This is a more severe example of a vernal ulcer showing a large area of central ulceration with established plaque formation .
This image illustrates the non wetting properties of the plaque and the raised epithelial edge, which is indicative of poor healing in the
presence of plaque. Peripheral to the ulcer, the cornea is relatively clear although corneal vascularization from the limbus has commenced.
The conjunctiva is hyperaemic and a strand of typically 'stringy' mucus lies on the surface of the eye.

GIANT PAPILLARY CONJUNCTIVITIS

Fig. 5.15 Giant papillary conjunctivitis is a chronic condition affecting the upper tarsal conjunctiva; it is caused by mechanical irritation.
The condition is seen, for example, in patients wearing contact lenses, ocular prostheses or in association with protruding nylon suture ends
following corneal or cataract surgery. Patients complain of itching, ocular discomfort and a stringy discharge. The aetiology appears to be
mast cell degranulation initiated by mechanical trauma. In this example, a hard contact lens has produced giant papillae at the m edial end
of the upper border of the tarsus with a fine papillary reaction elsewhere. The condition is clinically distinguishable from vernal
conjunctivitis by the lack of changes elsewhere in the conjunctiva, absence of an atopic history, and the presence of an associated foreign
body. The conjunctival changes resolve with removal of the irritating stimulus.
124 ALLERGIC EYE DISEASES, EPISCLERITIS AND SCLERITIS
OCULOCUTANEOUS CICATRICIAL DISORDERS
This is a heterogenous group of conditions in which the skin,
eye and mucous membranes are damaged through immune
reactions giving rise to, amongst other effects, a cicatrizing
conjunctivitis. Included in this group are cicatricial
pemphigoid, erythema multiforme or Stevens- Johnson
syndrome, linear IgA disease, dermatitis herpetiformis and
OCULAR CICATRICIAL PEMPHIGOID
This autoimmune disorder is caused by autoantibodies to
mucosal basement membrane. About 70 per cent of patients
presenting with cutaneous pemphigoid have ocular changes,
whereas in those presenting with ocular disease about 20 per cent
have cutaneous disease. The condition usually presents to the
ophthalmologist in elderly women as bilateral chronic
conjunctival inflammation; the presentation is acute in a
minority, and in some follows conjunctival or lid surgery. The
clinical diagnosis of pemphigoid is suggested by the presence of
one or more of the other features of the disease, which include
scalp lesions and oesophageal, buccal and genital ulceration. Not
all features may be present, nor are they necessarily all active
simultaneously, but it may be possible to find scarring as
evidence of earlier activity.
hyperaemia
loss of caru ncl e
Fig. 5.16 Ulceration of the conjunctiva in active mucous membrane pemphigoid is clearly delineated in this case following instillation of
fluorescein .
some drug-induced disorders. The diagnosis, which involves the
cooperation of ophthalmologist and dermatologist, may depend
on tissue biopsy and immunohistochemistry. Bulbar
conjunctival biopsies can be taken without risking disease
exacerbation and biopsy of skin or other mucosal lesions may
also 'be useful to support a diagnosis .
The clinical course is of progressive conjunctival shrinkage
with acute inflammatory exacerbations. Patients need to be
assessed for the degree of conjunctival fibrosis and the amount of
active inflammation. In the early stages there is symblepharon
formation in the lower fornix, with loss of the caruncle. With
active disease, areas of conjunctival ulceration stain with
fluorescein and resolve with further scarring. Progressive
conjunctival scarring leads to increasing symblepharon
formation, entropion and tear film instability, which in turn
causes corneal opacification. In mild, slowly progressive disease,
therapy may not be justified. First-line treatment is with dapsone
or sulfapyridine, but severe progressive disease may require more
potent systemic immunosuppressive drugs.
 OCULOCUTANEOUS CICATRICIAL DISORDERS 1~

Fig. 5.17 Extensive palatal ulceration is visible in this edentulous

patient (left). The painful mouth ulcers had been erroneously
palatal ulceration attributed by the patient to poorly fitting dentures. Buccal mucous
membrane pemphigoid (right) is also characterized by tongue
involvement, as in this patient in whom blisters are seen alongside
sloughing ulcers, which indicate the site of a previous blister.
By courtesy of Dr F M Tatnall.

early
..,-------1 symb lepharon

loss of
fornix

Fig. 5.18 In early pemphigoid, conjunctival cicatrization usually obliterates the caruncle (top left), producing progressive loss of the fornices
and symblepharon formation. This example (top right) shows symblepharon formation in early disease which has been arrested by therapy.
Inexorable progression to late disease is associated with scarring that almost obliterates the inferior fornix (bottom left).
 Fig. 5.19 This example illustrates a late stage of ocular cicatricial
pemphigoid with gross symblepharon formation, corneal scarring
and vascularization resulting from corneal drying. This is
associated with loss of tears and mucus-producing cells in the
conjunctiva. The lashes have been removed during the course of
the disease to prevent further corneal trauma from trichiasis and
cicatricial entropion.

linear
immunofluorescence
""'1"5~:i:ii':J at conjunctival
basement membrane

Fig. 5.20 Histological examination of the conjunctiva in mucous

membrane pemphigoid.

ERYTHEMA MULTIFORME

Erythema multiforme is an immunologically mediated vasculitis

that produces focal lesions in the skin and, in its variant known
as Stevens-Johnson syndrome, in the mucous membranes. The
condition frequently follows the administration of drugs, such as
sulfonamides or phenobarbitone, or bacterial and viral
infections, such as herpes simplex. The disease is characterized
by its acute onset and lasts 2- 3 weeks, during which time
complete resolution occurs. In some cases, serious complications Fig. 5.21 The rash
(e.g. renal failure) may develop. of erythema
multiforme starts on
the extensor surfaces
of the arms and legs,
and spreads to
involve the trunk.
The skin lesions
consist of an area of
erythema
surrounding a paler
centre, which may
ulcerate to give a
'target' appearance.
The lesions heal
without scarring.
 OCULOCUTANEOUS CICATRICIAL DISORDERS 1

Fig. 5.2~ In its more severe form, with mucous membrane

involvement, erythema multiforme is known as Stevens- Johnson
syndrome. This patient shows extensive oral ulceration involving
the upper and lower lips. Patients are acutely ill, losing serum and
protein through their skin; they are unable to eat and at grave risk
of secondary infection. Systemic steroids, fluid replacement and
prophylactic antibiotics are the basis of treatment.

Fig. 5.23 Stevens- Johnson syndrome produces focal ulcerative changes in the conjunctiva where a severe pseudomembranous
conjunctivitis may also occur in the acute stages. In the resolving phase healing is accompanied by scar formation which is typically focal, as
seen here on the lower tarsus. The ocular surface is affected as a secondary phenomenon due to tear film changes.

Fig. 5.24 Symblepharon formation is a frequent result of conjunctival involvement in erythema multiforme. In this example a fibrous
band is seen at the medial canthus, stretching from the lower punctum across to the bulbar conjunctiva. These symblephara are narrow, in
contrast to the broad bands of ocular pemphigoid.
28 ALLERGIC EYE DISEASES, EPISCLERITIS AND SCLERITIS

thickened
epithelium

Fig. 5.25 Histological changes in end-stage erythema multiforme may be similar to those seen in mucous membrane pemphigoid. Patchy
epidermidalization of the conjunctiva has taken place as evidenced by rete ridge formation, thickened epithelium with a prickle cell layer,
and keratin formation giving the histological appearance of skin without hair follicles or other appendages. The underlying stroma shows
marked fibrosis . In the acute phase of the disorder a mononuclear cell infiltrate in the stroma would be characteristic.

GRAFT VERSUS HOST DISEASE

Chronic graft versus host (GVH) disease occurs following bone mucous membranes including the mouth, oesophagus and
marrow transplantation for conditions such as acute myeloid conjunctiva that progress to cicatrization. Patients usually present
leukaemia and may cause inflammatory lesions of various with dry eye symptoms.

subepithelial
fibrosis

Fig. 5.26 This patient developed GVH disease that was treated successfully by immunosuppressive therapy 12 months after bone marrow
transplantation. The scarring on the upper tarsus shown in this picture has persisted unchanged for 10 years, puncta! occlusion and
intensive artificial tear supplements were required to maintain the corneal surface.

EPIDERMOLYSIS BULLOSA
This is a group of rare, recessively inherited disorders in which
basement membrane defects in the skin and mucous membranes
OCUlAR SURFACE DISORDERS
A healthy ocular surface is an essential requirement for precise
corneal refraction and transparency and for the protection of the
globe from disease. It is maintained by the total environment
provided by the eyelids, conjunctiva and adnexal secretory
glands; the malfunction of any element can lead to secondary
ocular surface disease. The tear film consists of an inner film of
mucus secreted by the goblet cells, a middle layer of watery tears
secreted by accessory lacrimal glands in the conjunctiva and an
oily superficial layer secreted by the meibomian glands along the
lid margin. Recent studies have shown that the mucous layer is
the major constituent. It maintains even wetting of the ocular
OCULAR SURFACE DISORDERS 1
are associated with severe scarring m relationship to minor
trauma.
Fig. 5.27 Scarring of the hands is severe in children with
epidermolysis bullosa. They also develop oral, oesophageal and
anal strictures. Great care is required during both examination and
anaesthesia to prevent further skin damage from minor trauma.
~'<'<--".=-~""=.,....---1 lateral upper lid
symblepharon
Fig. 5.28 Children develop symblepharon, particularly at the
medial and lateral canthi. Recurrent corneal erosions are common
and are associated with a fine subepithelial scarring.
surface; the watery layer provides oxygen and nutrition to the
conjunctiva and corneal epithelium and the oily film retards
evaporation and maintains the optical integrity.
The examination of patients with ocular surface disease
includes an assessment of dynamic lid function-lagophthalmos
(defective lid closure), eyelid blinking or abnormal lid
architecture-and an inspection of the whole conjunctival and
corneal surface should be carried out. Frothy tears indicate
excessive meibomian gland secretion, which may destabilize the
tear film.
130 AllERGIC EYE DISEASES, EPISClERITIS AND SClERITIS

~---Aqueous

~----'---M u cin

Fig. 5.29 The adequacy of the precorneal tear film may be

judged qualitatively by the presence of excess debris or mucus, a
decrease in the marginal tear meniscus and a shortened break-up
time of the fluorescein-stained tear film.

Fig. 5.30 Schirmer's test is useful in documenting tear

production, although the results cannot always be correlated to
symptoms. In the absence of local anaesthesia, a normal value is
greater than 6 mm at 5 min.

Fig. 5.31 Dessicated

epithelium stains with
Bengal Rose dye; the
degree of staining can
be used to grade the
severity of epithelial
disturbance on the
medial and lateral
conjunctiva and
cornea.
Adapted from A J Bran,
Doyne Lecture.
Reflections on the tears.
1997; 11:583- 602.
 OCULAR SURFACE DISORDERS 131

KERATOCONJUNCTIVITIS SICCA

Tear film deficiency is a balance between the relationship of
deficient secretion and evaporation. Keratoconjunctivitis sicca is
a common cause of chronically irritable sore eyes that usually
occurs in late middle-aged and elderly women owing to a gradual
reduction in lacrimal secretion. Similar symptomatology and
findings may be present in other conditions in which other
components of the normal tear film, such as mucus and
meibomian lipid, are reduced or absent. Dry eyes have a deficient
or unstable tear film which contains mucus and debris and has a
poor or absent meniscus at the lid margins. In severe cases,
filaments of mucus can be seen attached to the cornea; these
exacerbate the symptoms. Apart from idiopathic
keratoconjunctivitis sicca, similar changes are seen with
rheumatoid arthritis, Sjogren's syndrome, sarcoidosis and
localized conjunctival disease caused by trauma, infection or
drugs. A particular feature of dry eye disease is the disparity
between the severity of symptoms and the apparent lack of
abnormal 'signs.

conjunctival
hyperaem ia

Fig. 5.32 The clinical picture of keratoconjunctivitis sicca shows diffuse punctate epithelial erosions over the lower one-third of the
corneal epithelium that stain as red spots with Bengal Rose. The staining usually extends on to the lower bulbar conjunctiva in the exposure
area. In this patient there is some associated conjunctival hyperaemia.

Fig. 5.33 In severe keratoconjunctivitis sicca, threads of dried mucus and epithelial cell debris become attached to the corneal
epithelium. This condition is known as filamentary keratitis. Bengal rose stains mucus and devitalized cells; in this example it is seen
staining the filaments more avidly than fluorescein, which has also been instilled. Filamentary keratitis produces severe discomfort and
photophobia. Treatment lies in tear film augmentation and topical mucolytic agents.
By courtesy of Professor R J Buckley.
ALLERGIC EYE DISEASES, EPISCLERITIS AND SCLERITIS
SJOGREN'S SYNDROME
Sjogren's syndrome is typically seen in elderly women and is characterized by a combination of dry eyes, dry mouth and, frequently,
rheumatoid arthritis. Patients should also have a serum autoantibody screen which is positive for the extractable nuclear antigens SS-A
and SS-B.
Fig. 5.35 This patient illustrates the typical changes of dry eyes
and mouth associated with Sjogren's syndrome. Patients also have
a small but statistically significant risk of developing a lymphoma.
Mild cases respond to treatment with wetting agents. Occlusion of
the lacrimal puncta by plugs or cautery alleviates symptoms in the
more severe cases.
SUPERIOR LIMBIC KERATOCONJUNCTIVITIS
Superior limbic keratoconjunctivitis is an ocular surface disorder
in which the predominant changes occur in the superior limbus
and tarsal conjunctiva. Most cases are associated with a history of
dysthyroid eye disease although the precise pathogenesis remains
uncertain as some patients have no other associated pathology. It
is possible that changes in intraorbital pressure or defective
Fig. 5.34 The commonest association of keratoconjunctivitis
sicca is rheumatoid arthritis. Among sufferers of the disease, 15 per
cent may be expected to develop dry eyes, although usually not
severely. This example shows the changes associated with advanced
rheumatoid arthritis of the hands including the swollen
metacarpophalangeal joints, ulnar deviation, swan-neck deformities
of the fingers and the skin changes associated with vasculitis and
steroid therapy.
chronic
inflammatory h~~~.
cell infiltrate
Fig. 5.36 A biopsy of the lip mucosa confirms the diagnosis of
Sjogren's syndrome by demonstrating a chronic inflammatory
infiltration of the labial accessory salivary glands.
By courtesy of Dr PH McKee.
blinking due, for example, to upper lid retraction produce a
mechanical alteration in the normal lid-globe interaction leading
to surface cell damage of the conjunctiva and upper cornea that
is best demonstrated by staining with Bengal Rose. The
symptoms of ocular discomfort can usually be relieved by wetting
agents.
 OCULAR SURFACE DISORDERS

Fig. 5.37 This patient, who had previously been treated for
thyrotoxicosis, presented with a history of sore eyes for many
months. There is some lid oedema and lid retraction.
Fig. 5.38 Rose bengal drops have been instilled into both eyes,
which demonstrate the characteristic upper limbal staining from
the 10 o'clock to the 2 o'clock positions in each eye. Typically,
there is bilateral involvement which is best seen in the position of
downgaze. The changes are more marked in the left eye, where a
diffuse limbal infiltration extends on to the cornea and upwards on
to the bulbar conjunctiva.

Fig. 5.39 This patient demonstrates a less severe example in

which the changes are limited to scattered punctate staining of the
limbus associated with mild hyperaemia. Examination of the
superior tarsal conjunctiva shows mild hyperaemia and some
papillae.

NEUROTROPHIC KERATITIS

Fig. 5.40 Neurotrophic keratitis results from partial or complete corneal denervation. Soon after denervation the surface epithelial cells
of the cornea and conjunctiva lose their microvillae which hold the mucin layer of the tear film. The tear film becomes unstable because of
the nonwetting surface and the eye is very vulnerable to infection and minor trauma. In this example there is a shallow ulcer due to loss of
epithelium and the surrounding epithelium is grey and unstable. Botulin toxin-induced ptosis, a gold weight in the upper lid or a
permanent tarsorrhaphy may prove necessary for corneal protection.
ACCERGIC E t E DISEASES, EPISCLERIIIS AND SUE RillS

loss of brow wrink les

gold we ight in lid

l~ 0'J
-I --+t-----1 loss of fa ci al w ri nkles
( ~

\~

Fig. 5.41 Neurotrophic keratitis is a particularly severe problem when sensory V

nerve lesions are combined with the motor deficit from a lower motor neurone VII
palsy. A common cause is a cerebellar pontine angle tumour such as an acoustic
neuroma.

SOLAR AND CLIMATIC EXPOSURE

Excessive exposure to outdoor conditions, and especially and localized inflammation. Translucent deposits can be seen in
ultraviolet radiation, is associated with degenerative conjunctival the corneal stroma. (See also Fig. 6.44.)
changes that produce an irritable eye from tear film disturbance

Fig. 5.42 Pingueculae are raised yellowish patches that enlarge gradually until they abut the cornea but do not encroach upon it.
Histologically they are formed by elastotic degeneration of collagen within the substantia propria.
 OCULAR SURFACE DISORDERS

Fig. 5.43 A pterygium is a raised triangular area of bulbar conjunctiva that grows over the superficial cornea and produces visual
symptoms either from direct encroachment on the pupil or from irregular astigmatism. Pterygia normally occur on the nasal bulbar
conjunctiva. This is thought to be caused by the cornea focusing on lateral light from the temporal side on the nasal limbus damaging the
nasallimbal stem cells. In temperate climates pterygia progress only very slowly and rarely cause visual symptoms but in sunny, hot, dusty
regions of the world they can represent a serious threat to vision. Examination of the leading edge and body of the lesion shows whether
the pterygium is active by the degree of vascular engorgement in the bulk of the lesion. These pterygia are quiescent: the eye is white, they
are not inflamed and the vessels in the lesion are not engorged. Surgical removal is indicated if visual impairment is threatened or if the
lesion causes discomfort but the recurrence rate is high, particularly if solar exposure continues. Postoperative recurrence can be reduced
by using a conjunctival graft.

Fig. 5.44 Histological examination shows that the pterygium

consists of hyalinized subepithelial collagen with elastotic
degeneration. At the apex of the pterygium on the cornea there is
fragmentation and destruction of Bowman's layer. Similar, but less
vascular, changes are seen in a pinguecula (which probably
represents the initial stage of the disease).
136 ALLERGIC EYE DISEASES, EPISCLERITIS AND SCLERITIS

NUTRITIONAL XEROPHTHALMIA

Nutritional xerophthalmia is one of the two main clinical
manifestations of vitamin A deficiency. Vitamin A is a fat-soluble
vitamin found in eggs, heart and liver which in humans can also
be synthesized from the carotenoids found in yellow and green
vegetables. Night blindness is the first sign of deficiency. About
five million children suffer from xerophthalmia due to vitamin A
deficiency annually with 250 000 becoming blind. Ironically, this
condition is common in areas where vegetables containing
carotenoids are plentiful but not eaten for social or economic
reasons. It usually affects children below 4 years of age who have
stopped breastfeeding. Protein and caloric deficiency and
secondary systemic and ocular infections compound the vitamin
deficiency leading to a high mortality rate from bowel and
respiratory infections.

Fig. 5.45 In the vitamin A-deficient eye there is a drying and wrinkling of the conjunctiva associated with the development of Bitot's
spots. These spots are small, white, cheese-like patches which may have a foamy appearance and do not wet easily. At this stage a punctate
keratopathy may also appear.

epithelial border

Fig. 5.46 This photograph shows a late stage in the development of vitamin A deficiency in which the corneal epithelium is lost over the
lower nasal part of the exposed eye. Note the dry, wrinkled conjunctiva.
 OCULAR SURFACE D

---'--il--4__::,..,...~ conjunctival
keratinization

Fig. 5.47 In advanced keratomalacia the whole cornea becomes softened and opaque. At this stage, the clinical picture is often
complicated by secondary infection; in this case, secondary infection has resulted in perforation of the globe and endophthalmitis.
By courtesy of D r A S ommer.

thickened . ~.· - · ·• '"~" ): '_,( './ '0·....) ._;·:

epithelium .. , '"'' ~ .!> .~z-~. ~·~~!.,·a;.;'-0.;.._- . ..,-=~ basal epithelium

~~~~¢! . . . - ~ . ~ ,- ~o.. . _r ·
(;" .... -......:-.:.-
- - 4 - ;_ . ~;-:---::--. :: :!(i
stroma
a....:.o\. .---- -.->, " . . ~.

Fig. 5.48 The histological appearance of the conjunctiva in advanced keratomalacia shows thickened keratinized epithelium. Goblet cells
are lost
By courtesy of Dr A Sommer.
 DISEASES OF THE SCLERA AND EPISCLERA

The most common and important forms of scleral disease are the
inflammatory disorders of scleritis and episcleritis. The sclera is
composed of collagen and elastic fibres, and is subject to the
range of disease processes that affect connective tissue elsewhere
in the body- hence its association with chronic inflammatory
joint disease and the vasculitides such as rheumatoid arthritis,
Wegener's granuloma, SLE, polyarteritis nodosa and
polychonditis. The episclera (Tenon's capsule) acts analogous to
a synovial membrane for smooth movement of the eye. It has a
fibroelastic connective tissue structure covering the sclera and
carries a vascular network that consists of a deep and a superficial
plexus. Scleritis is always accompanied by overlying episcleritis.

Posterior
conjunctival
Superficial marginal artery
plexu s Superficial
Cornea episcleral plexus

Deep
episcleral plexus Fig. 5.49 The vascular supply of the anterior episclera and sclera
Anterior ciliary are best examined at the slit lamp. The importance of
artery understanding the vascular anatomy lies in the clues that it
-:;;;;;;;::::=~==~~ Tenon's
Parietal layer of
capsu le
provides in differentiating the clinical patterns of inflammation
with episcleritis and scleritis. Three layers of vessels are visible. The
Muscle conjunctival plexus is the most superficial layer and can be
distinguished clinically by its ability to be moved over the
Visceral layer of
Tenon's capsule underlying structures. The superficial episcleral plexus is a radially
arranged series of vessels within Tenon's capsule that anastomose
at the limbus with the conjunctival vessels and the underlying deep
episcleral plexus that is closely applied to the sclera. The vessels in
this layer are arranged in an irregular, reticular, nonradial fashion
and, unlike the conjunctival and superficial layers, are not blanched
by a drop of 1 : 1000 epinephrine.

EPISCLERITIS

Episcleritis is a benign self-limiting inflammation that occurs in
young adults. It may be bilateral. The presenting features are
acute redness and mild discomfort with occasional watering.
Severe pain and photophobia are not characteristic features and,
if present, suggest scleritis. Episcleritis is transient, recurrent and
nondestructive. Most patients have no associated systemic
disease but episcleritis may be associated with allergic, infectious
or drug-related diseases sometimes with seronegative
arthropathies and vasculitic diseases. Episcleritis may be diffuse
or nodular, the latter form tends to be more symptomatic.
Treatment with topical steroids or nonsteroidal agents is effective
in shortening the duration of the condition.

Fig. 5.50 Diffuse episcleritis may affect a sector or the whole

anterior segment of the globe. In this example the radial superficial
episcleral vessels are dilated and, although there is some associated
engorgement of the conjunctival and deep episcleral plexus, there
is no scleral swelling or oedema.
 DISEASES OF THE SCLERA AND EPISCLERA 13

nodu le surro un ded

""'-,-------,6+-------+-"t&--1 by f oca l vascular
eng orgement

Fig. 5.51 In nodular episcleritis the oedema and infiltration of the episclera are localized to one or more sites with engorgement of
episcleral vessels around a central pale nodule. The nodules are mobile over the underlying sclera, they are not really tender and there is no
scleral oedema. Resolution of nodular episcleritis tends to occur more slowly than in diffuse episcleritis and topical steroids or nonsteroidal
anti-inflammatory drugs may help.

scle ral oedema

Fig. 5.52 The conjunctival vessels and superficial episcleral vessels can be blanched by a drop of 10% phenylnephrine or 1 : 1000
epinephrine, which is useful in differentiating scleritis from episcleritis as the deep episcleral plexus and the scleral oedema are seen more
easily. The superficial episcleral plexus has a radial distribution; this is helpful in distinguishing the vascular changes of episcleritis from the
more net-like deep episcleral plexus.
AtttHUIC E t E DISEASES, EPISCLERIIIS AND SCLERI I IS

SCLERITIS

Scleritis, unlike episcleritis in which resolution takes place

without damage, is a potentially destructive disease. Four clinical
types are recognized: diffuse anterior, nodular anterior,
necrotizing anterior with or without inflammation (scleromalacia
perforans), and posterior scleritis. Scleritis causes redness,
watering and photophobia but is distinguished from episcleritis
by pain which may be severe. There is dilatation and
engorgement of the deep episcleral plexus which is displaced
forwards by scleral oedema. The lesions are tender to touch and
usually have a purplish tinge because of venous engorgement.
Deep episcleral biopsies (which are not without risk) show
scleritis to be an immune-mediated vasculitis; necrotizing
vasculitis is the result of fibrinoid necrosis of the vessel wall,
thrombotic vascular occlusion and chronic inflammation. All
scleritic lesions need to be examined for areas of capillary closure
which is the earliest sign of necrosis. The majority of patients
with necrotizing scleritis have an underlying identifiable
causative systemic factor as do one-third of patients with the
diffuse form of the disease. Necrotizing scleritis is associated with
such diseases as rheumatoid arthritis, systemic lupus
erythematosus, Wegener's granuloma, polyarteritis nodosa,
relapsing polychronditis and Crohn's disease.
Diffuse and nodular anterior scleritis usually responds to
systemic therapy with nonsteroidal anti-inflammatory agents
such as flurbiprofen, although systemic steroids may be required
for severe cases. Topical steroids may provide symptomatic relief
but do not affect the underlying disease process. After resolution, Fig. 5.53 Diffuse anterior scleritis is the commonest and least
increased transparency of the sclera and thinning of the collagen severe form of scleritis accounting for up to 50 per cent of cases. It
network can be seen. can be widespread or confined to one quadrant.

corneal ulceration

Fig. 5.54 A small number of patients may progress to necrotizing changes with repeated attacks. This patient with rheumatoid arthritis
shows active scleritis with scleral thinning. The eye is dry with mucus in the tear film and a small area of central corneal ulceration stained
with fluorescein .
 DISEASES OF THE SCLERA AND EPISCLERA 14

Fig. 5.55 Nodular anterior scleritis is the second most common

type of scleritis. It may appear to be similar to nodular episcleritis
on superficial examination but the nodules are tender, associated
with scleral swelling and cannot be moved over the tissues. Initial
attacks resolve with out scleral destruction but about 20 % of
patients progress to necrotizing disease with repeated attacks.

-'-',ZZ.------1 granulomatou s nodule

in equatorial sc lera

Fig. 5.56 Histological examination of an enucleated eye showing

a granulomatous nodule in the equatorial sclera.
 E E DISEASES, EPISCLERITIS AND SCLERITIS

.,:.--..c.;-----,:- --1 necrotizing scleritis

,.-..-~"""' :,:.. ·. / ·:

Fig. 5.57 Necrotizing anterior scleritis is the most serious form of scleritis and is usually very painfuL The first indication of necrotizing
change is vasa-occlusion or venular shutdown in areas of scleral inflammation. These areas are pale, even though the eye still appears
congested. Vascular closure is followed by scleral thinning and bluish changes or scleral infarction when the affected area becomes white
and sloughs. Unless the scleritis is adequately and promptly treated the condition will progress with increasing tissue destruction and
potential loss of the eye. The management of these patients is difficult as they are often ill from systemic disease and the side-effects of
treatment. High-dose oral or intravenous steroids are needed and cyclosporin, methotrexate or cyclophosphamide can be effective in
recalcitrant cases. This patient shows an area of vascular closure that progressed to necrosis and ulceration 10 days later.

peripheral
co rneal gutter

white eye

Fig. 5.58 Necrotizing anterior scleritis without inflammation, also known as scleromalacia perforans, is characterized by painless
progressive thinning of the sclera in the absence of symptoms and with minimal inflammatory signs as a result of arteriolar occlusion of the
deep episcleral vascular network. Pathologically there is infarction and sequestration of the affected area. It is nearly always associated with
severe long-standing seropositive rheumatoid arthritis. In this example, the scleritis has resulted in conjunctival ulceration and guttering of
the adjacent cornea, possibly as a dellen.
 DISEASES OF THE SCLERA AND EPISCLER

Fig. 5.59 Patients with scleromalacia perforans usually have severe long-standing
rheumatoid arthrits. This patient (the same one as in Fig. 5.58) has a left 12th nerve palsy
from cervical arthritis.

Fig. 5.60 After resolution of an anterior diffuse necrotizing

scleritis in a patient with Wegener's granulomatosis, the eye shows
scleral thinning. On slit-lamp examination, rearrangement of the
remaining collagen bundles can be seen with changes in the
vascular pattern over the lesion and at the limbus.

Fig. 5.61 Scleral thinning allows the dark choroidal pigmentation

to be seen. Staphylomas usually result from raised intraocular
pressure in the presence of scleral thinning. Perforation of the
globe is rare in the absence of trauma.
144 ALLERGIC EYE DISEASES, EPISCLERITIS AND SCLERITIS

epithelia l edge

stroma l melting
underlying f-T-----'--¥~~­
epithelial defect

Fig. 5.62 In this patient keratitis involves the whole

circumference of the peripheral cornea (top left). Corneal stromal
melting can be seen on lateral gaze (top right). With resolution of
inflammation following systemic immunosuppression, an
epithelialized peripheral corneal gutter persists (left).
 DISEASES OF THE SCLERA AND EPISCLERA 145

scleritis mainly at the

limbus- a common
reason for the
development of sclerokeratitis
secondary glaucoma

Fig. 5.63 Sclerokeratitis may complicate an anterior scleritis when a diffuse peripheral opacity can be seen in the adjoining corneal
stroma. In active disease, the whole thickness of the corneal stroma adjacent to a patch of scleritis may melt and ulcerate. Impending
perforation may require a tectonic peripheral corneal transplant. This type of active limbitis is often accompanied by an acute rise in
intraocular pressure and KP on the adjacent corneal endothelium.

macular folds

Fig. 5.64 The diagnosis of posterior scleritis is frequently overlooked. The patient presents with ocular pain and visual loss from
exudative retinal detachment, macular oedema or disc swelling. Although some patients have anterior involvement, inflammatory signs may
be minimal and apparent only if the posterior sclera is examined by getting the patient to look in extreme gaze. With severe inflammation,
there may also be proptosis and extraocular muscle involvement and the differentiation from orbital myositis or pseudo-tumour becomes
difficult and perhaps academic. Fundus examination of a relatively mild case here shows slight optic disc swelling and subretinal fluid
producing macular folds.
AllERGIC EYE DISEASES, EPISCLERITIS AND SCLERITIS

=~---l iens

th ickened sclera
oedema in episcleral space

Fig. 5.65 B-scan ultrason ography is the most effective way of

diagnosing the condition by demonstrating thickening of the sclera
and separation of the episclera as a result of the inflammation .
Exudative retinal detachment can also be detected by this method.
The Cornea
Stephen Tuft

The Normal Cornea

Congenital Corneal Anomalies
Corneal Dystrophies
Corneal Ectasia
The lridocorneal Endothelial Syndrome
Corneal Epithelial Stem Cell Failure
Corneal Post-inflammatory Changes and Degenerations
Corneal Trauma
Microbial Keratitis
Corneal Thinning and Melting Disorders
Corneal Changes from Metabolic Disorders and Medications
Refractive Surgery
Corneal Transplantation and Rejection
148 THE CORNEA

THE NORMAL CORNEA

The cornea has three primary functions. These are:
• the refraction of light- the main refractive interface being
between air and the precorneal tear film
• transmission of light with a minimum of distortion, scatter
and absorption
• the structural support and protection of the globe without
compromising the optical performance.
To achieve these functions the cornea has evolved as an avascular
structure with metabolic requirements supplied by diffusion. The
main supply of oxygen to the epithelium and stroma is provided
by atmospheric oxygen dissolved in the tear film with a small
contribution from the limbal vessels peripherally; the endothelium
obtains oxygen primarily from the aqueous. Glucose is similarly
supplied from the tear film and aqueous. Aerobic metabolism
produces carbon dioxide, which either diffuses away through cell
membranes or is converted to bicarbonate and pumped into the
aqueous by a carbonic anhydrase-dependent pump at the
endothelial cell surface. Lactic acid, produced by anaerobic
metabolism, cannot easily diffuse through the epithelial cell
barrier and most diffuses posteriorly into the aqueous; corneal
hypoxia leads to an accumulation of lactic acid and metabolic
acidosis which contributes to corneal oedema.
The corneal epithelium is derived from surface ectoderm but
the other corneal structures are formed from neural crest. After
invagination of the lens vesicle, a layer of loose collagen fibrils
between the ectoderm and the lens represents the corneal
stroma. Mesenchymal cells from the perilimbic cell mass begin to
form endothelium, and the stroma is invaded by perilimbic
fibroblasts (future keratocytes) at about 6 weeks of gestation. At
birth the cornea is relatively large compared to the rest of the
globe and adult size is attained by about 2 years of age.
The cornea has a horizontal diameter of 11 - 12 mm that is
reduced to 9- 11 mm vertically by encroachment of the limbus.
The central corneal thickness is 0.52 mm (normal range
0.49- 0.56 mm) increasing to 0.7 mm peripherally. The central
cornea has an anterior radius of curvature of 7.8 mm (43.5d)
(normal range 7.0-8.5 mm, 39.5- 48d) and a posterior radius of
curvature of 6.8 mm (49.5d). The posterior surface faces the
aqueous, which has a lower refractive index (1.336) so that the
refractive power of this surface is about -6D. The average
refractive index of the cornea is 1.376 and the axial refractive
power is approximately 43D, which is about 74 per cent of the
total dioptric power of the human eye.

epithelium {;~~epithelial
' ·- ' .• · ".
· ·· · ·· · · · ·
i -X basement membrane
Bowman' s layer

stroma

· ··z Descemet's membrane

:6:::6::======~
· .;:.
·=
·· endothelium

Fig. 6.1 The cornea has five distinct histological layers. The epithelium supports
the precorneal tear film and consists of a stratified squamous cellular layer attached
to an underlying basement membrane. Bowman's layer is an acellular condensation of
superficial stroma approximately 10-20 ~-tm thick that lies immediately beneath the
epithelial basement membrane. The stroma forms over 90 per cent of the corneal
thickness and consists of regularly spaced collagen lamellae (layers) in a proteoglycan
matrix interspersed with keratocytes. Descemet's membrane is composed of a lattice
of collagen fibrils that is 3~-tm thick at birth and increases in thickness with age. The
endothelium is a monolayer of hexagonal cells.
By courtesy of Professor J Marshall.
 THE NORMAL CORNEA

Fig. 6.2 The precorneal tear film must be smooth and stable for
regular refraction. The epithelial surface is thrown into multiple
folds (microvilli and microplicae) which produce a glycocalyx (a
branching mucoprotein layer) that renders the surface hydrophilic.
The precorneal tear film is about 40 J.lm thick and is composed of
mucus derived from the conjunctival epithelial cells, conjunctival
goblet cells and the lacrimal glands. The aqueous component is
secreted by the lacrimal glands and the superficial lipid layer from
the meibomian glands. Atmospheric oxygen, metabolites and
antimicrobial agents (e.g. IgA, lysosyme, lactoferrin) are dissolved
in the tear film.
By courtesy of Professor J Marshall.

basement membrane

Fig. 6.3 The epithelium is about five cells thick and separated
from Bowman's layer by the epithelial basement membrane. The
morphology of the basal cells changes as they migrate anteriorly to
become intermediate wing cells and then elongated superficial cells
with flattened nuclei that finally desquamate from the surface into
the tear film. Macrophages (dendritic cells) are found in the
epithelium having migrated from the limbus although they may be
absent in the central zone . These have an antigen-presenting
function. The epithelium has zonula occludens junctions between
cells which make the healthy epithelium a virtually impermeable
barrier.
By courtesy of Professor J Marshall.

Fig 6.4 Cells from the corneal limbus continuously replace cells
lost from the corneal epithelium. A population of stem cells is
thought to be located in the basal epithelial cells of the folds of the
palisades of Vogt. The stem cells divide to form 'transient
amplifying cells' that move toward the centre of the cornea.
Postmitotic daughter cells then migrate anteriorly from the basal
layer to become terminally differentiated cells that are eventually
lost from the anterior surface of the epithelium into the tear film.
 Fig. 6.5 The mechanical strength of the
cornea is provided by the stroma, which is
formed predominantly of collagen fibrils
(mainly type 1) maintained in a pro teo glycan
matrix. The stromal fibrils are continuous from
limbus to limbus and are arranged into about
200 layers or 'lamellae' with a small degree of
interdigitation. The superficial Bowman's layer
is acellular and the collagen fibrils are finer and
more densely packed. Transmission oflight
depends on the collagen fibrils regular size and
spacing with small changes of refractive index.
A relative dehydration of the stromal
proteoglycans is required which is achieved
because the epithelium is impermeable and by
the endothelial pump which removes water
from the stroma. Light transmission is
maximal at 700nm (98 per cent) and decreases
to 80 per cent at 400 nm. Ultraviolet light with
a wavelength below 310 nm is strongly
absorbed by the stroma. By contrast, the
cornea transmits infrared radiation up to 2400
nm.
By courtesy of Professor K M eek.

Fig. 6.6 Using in vivo confocal microscopy high-resolution

images can be obtained in real-time at different depths within the
intact living cornea without the need for staining or processing,
giving a direct view of living cells. Shown here is the cellular
morphology of a normal human cornea. Each image represents an
optical volume with approximately 450 x 340 x 9 1-lm. a, Superficial
epithelial cells; b, wing epithelial cells; c, basal epithelial cells;
d, subepithelial nerves (on Bowman's layer); e, first layer of
keratocyte nuclei; f, nerve branch and keratocytes in the mid- ·
stroma; g, keratocytes in front of Descemet's membrane; h,
endothelial cells.
By courtesy of Dr T Moller-Pedersen.
 THE NORMAL CORNEA 15

child 1:.•. ~
=?"7·"'<';: : :)~:;-"::--,.7!.)-: :,=~,-----:--,-
C)
?
.. -..
_ ",~=""~
:-,--:_;:--_--j endothelium
Descemet 's membrane

?.
b• :

F
~ ;d ;;1;~::::'"'"'
t hickec De<cemet''

' '"" u =

Fig. 6. 7 Descemet's membrane, which consists of type IV collagen, is secreted by the endothelium. It is composed of a lattice of collagen
fibrils that is 311-m thick at birth (top), when the entire layer appears striated or 'banded'. A posterior 'nonbanded' layer is continuously laid
down throughout life so that Descemet's membrane increases in thickness with age to reach 30- 40 11-m in the elderly (bottom). Notice the
decrease in endothelial cell population.
By courtesy of Professor J Marshall.

Fig. 6.8 The endothelium can be examined by specular or

confocal microscopy. The endothelium does not replicate after
birth and cell counts reduce from 3500- 4000/mm 2 at birth to
approximately 2000- 2500/mm 2 in the adult cornea. Corneal
decompensation is likely with cell counts of less than 500/mm 2 •
Cell density is a good guide to function, which can be
complemented by other parameters such as variation in cell size
and morphology (polymegathism and polymorphism). These
specular photographs show the endothelium of an 18-month-old
infant (top) and a normal 74-year-old man (middle) . Notice the
decreasing cell count and larger cell size with age . Larger cells with
variation in morphology are seen in the endothelium of a patient
after traumatic cataract surgery (bottom).
52 THE CORNEA

NORMALCORNEALTOPOGRAPHY
The central 4 mm of the corneal surface is spherical but
progressively flattens towards the periphery (prolate curvature).
Keratometry measures the average curvature of the central 3 mm
along its two principal meridians. Topography, which can be
performed by reflection, projection or interference based
systems, measures the shape (curvature, power or elevation) of
the whole cornea.

Fig. 6.9 With topography (see Ch. 1) a series of concentric rings

is projected on to the surface of the corneal tear film . A difference
in the relative distances between these rings compared to a
calibrated spherical surface allows the corneal curvature to be
measured from the visual axis to the periphery; this is then
converted to dioptric power and displayed as a colour-coded
topographical map in which colours towards the red end of the
spectrum represent increasingly steep dioptric powers. A small
range of dioptric powers can be seen on this normal cornea with
flattening toward the periphery.

Corneal Statistics 75
SRI: -o.O Sill: O.li 60
PUll: 20/15 - 20/20
Sill I(; ii.l M IU / i1.3 M 21 +5
11in K: i1.3 x 20

I
'120
75 l05

Fig. 6.10 Astigmatism is seen on topography as distortion of the circular projections into oval reflections. Topography of regular
astigmatism appears as a 'bow tie' due to progressive peripheral flattening with axes at 90° to each other with mirror image symmetry
between the two eyes. Irregular astigmatism, as in keratoconus, appears as steepening below the visual axis (see Fig. 6.33) .
 THE NORMAL CORNEA 15:

AGE-RELATED DEGENERATION

Involutional changes as a result of ageing must be distinguished from pathological changes.

Fig. 6.11 The white limbal girdle ofVogt is a common ageing

change at the interpalpebral limbus which appears as a semilunar
opacity with a clear zone of separation from the limbus; it is best
seen by sclerotic scatter. The nasal cornea is affected nearly twice
as often as the temporal side. There may be clear patches in the
opacity, which may then resemble a mild form of band
keratopathy. Histological examination shows subepithelial hyaline
degeneration at the level of Bowman's layer.

Fig. 6.12 Anterior crocodile shagreen is a pattern of polygonal

opacities with intervening clear zones at the level of Bowman's
layer. It is best seen by wide-slit oblique illumination. Histological
examination shows folding of Bowman's layer. Although the
superficial variant is an ageing change, a pre-Descemet's form may
be familial and related to the central cloudy corneal dystrophy (of
Fran~Yois). Neither produces visual symptoms.

Fig. 6.13 Corneal arcus is due to the deposition of cholesterol

and other lipids in the peripheral cornea, particularly adjacent to
Bowman's layer and Descemet's membrane. It is a common ageing
phenomenon and is almost universal by the eighth decade. A sharp
clear zone lies between the limbus and the hazy inner border of the
arcus. The condition is usually of no significance unless seen in
patients under 40 years of age in whom it may be familial (arcus
juvenilis); these patients require investigation for hyperlipidaemia.
A lucent subepithelial zone with mild thinning may appear within
the arcus in elderly people (senile furrow degeneration).
 CONGENITAL CORNEAL ANOMALIES
Congenital abnormalities of corneal diameter that are not
associated with abnormality of thickness are rare and usually
inherited. A small-diameter cornea (microcornea) may be
associated with a small anterior segment of a small eye
(nanophthalmos). A large-diameter cornea (megalocornea) is
normally X -linked and must be distinguished from buphthalmos.
Associated ocular and systemic abnormalities are common.
Anterior segment dysgenesis produces a spectrum of
anomalies. The current clinical classification does not reflect the
underlying genetic defect. Both the Axenfeld- Rieger and Peter's
anomalies can be caused by abnormalities of at least four
different genes. Posterior embryotoxon, the mildest expression,
represents a centrally displaced Schwalbe ring. It is commonly a
normal variant and not associated with glaucoma. The
Axenfeld- Rieger syndrome (see Ch. 8) consists of posterior
embryotoxon with anterior iris adhesions, corectopia and iris
hypoplasia, probably due to arrest of neural crest development.
Peter's anomaly does not usually have posterior embryotoxon or
peripheral anterior iris adhesions but there is a central iris to
cornea adhesion with a defect of the endothelium and posterior
stroma. The significance of the Axenfeld- Rieger syndrome and
Peter's anomaly lies in their association with childhood
glaucoma, buphthalmos, corneal oedema and blindness. They
may also be associated with systemic defects such as dental and
cranial anomalies and malformations of the upper limbs and
spine. Posterior keratoconus causes thinning of the posterior
stroma with overlying haze and may be congenital; it has
therefore been classified as a dysgenesis although many cases are
thought to result from trauma. Congenital absence of the limbus
is often associated with flattening of the cornea, as is seen in
sclerocornea and cornea plana.
Fig. 6.14 Peter's anomaly is characterized by a central corneal
opacity with defects in the posterior stroma, Descemet's membrane
and endothelium and adhesions of the iris collarette to the
posterior cornea, making it difficult to see the lens. There may be
an anterior cataract or adhesions between the lens and cornea.
Secondary glaucoma is common. Associated cardiac defects, cleft
palate, craniofacial dysplasia and skeletal abnormalities may also
occur (Peter's-plus syndrome) . The defects can be explained by
abnormal separation of lens vesicle from surface ectoderm, and the
heterogeneity by organs being affected that differentiate at same
gestational age. The condition is usually bilateral with a sporadic
incidence (80 per cent), although inherited cases occur.
By courtesy of Professor P Khaw.
Fig. 6.15 Sclerocornea is a congenital nonprogressive
scleralization of the cornea. Either the peripheral cornea or the
entire cornea may be involved; the limbus cannot be identified and
the radius of curvature is flattened . There is overgrowth of
conjunctival and episcleral vessels on to the cornea. Opacification
of the cornea is due to a similar organization of the corneal stromal
collagen fibrils to those of normal sclera. The condition is usually
bilateral with an equal sex incidence and is usually sporadic,
although dominantly and recessively inherited forms have been
described. Cornea plana is an inherited abnormality most
commonly described in Finnish populations; the cornea is flat with
a radius of curvature similar to that of the sclera. The cornea is not
opaque unless associated with sclerocornea. Extreme hyperopia,
abnormalities of the angle and secondary glaucoma are common.
 CORNEAL DYSTROPHIES

CORNEAL DYSTROPHIES

The corneal dystrophies are inherited corneal diseases that
exhibit a remarkable degree of phenotypic and genetic
heterogeneity (Table 6.1). Molecular biology has given new
insights into the pathogenesis of these diseases. While at
present they are classified clinically or histopathologically,
their future classification is likely to be genotypic. It is evident,
however, that the distinction between some dystrophies is not
as clear as had been thought as apparently different clinical
appearances can be caused by mutations in the same gene.
Conversely, clinically similar dystrophies can result from
different genes on separate chromosomes determining
different protein products.
Many dystrophies are extremely rare and only the more
common types are illustrated here. Dystrophies that involve the
epithelium and anterior stroma may present with painful
recurrent epithelial erosions and reduced vision from scarring;
those involving the deeper cornea present only with loss of acuity.
Endothelial dystrophies may progress to cause corneal oedema.
Early or subclinical cases are sometimes found on routine
examination or by examining family members.

Table 6.1 Inheritance of corneal dystrophies

Condition Mode of inheritance Chromosomea Protein
Meesman corneal dystrophy AD 17q12 Keratin 12
Meesman corneal dystrophy AD 12q13 Keratin 3
Reis- Blickler's (COB 1) AD
Granular corneal dystrophy (CDGG 1)
Avellino corneal dystrophy (ACD)
5q31 (f3ig-h3) Keratoepith elin
Lattice corneal dystrophy type I (LCD1) AD
Lattice corneal dystrophy type Ill (LCD) AR
Lattice corneal dystrophy type II (Meretoja) AD 9q32-34 (GSN) Gelsolin
Thiel-Behnke (honeycomb) (CDTB) AD 10q24 Unknown
Macular corneal dystrophy (MCDC1) AR 16q22 CHST6
Gelatinous drop-like dystrophy (GOLD) AR 1p32-q12 M1S1
Schnyder crystalline corneal dystrophy (SCCD) AD 1p34.1-36.1 Unknown
Bietti crystalline corneoretinal dystrophy (BCD) AR 4q35 Unknown
Fuchs' corneal dystrophy (early onset) AD 1p32-34.3 Col 8A2
Peter's anomaly AD,AR 2p22-21 Unknown
Aniridia (AN 1) Peter's anomaly AD, AR 11 p13 (PAX6) PAX6 homeoprotein
Cornea plana (CNA 1, CNA2) AD,AR 12q21 Keratocan
Microphthalmia with sclerocornea AD,AR 14q32 Unknown
Keratoconus AD,AR 16q22.3-23.1 Unknown

' Genes are given in parentheses. AD , autosomal dominant; AR, autosomal recessive.

LINKAGES OF COMMON CORNEAL DYSTROPHIES

The linkages of some of the commonest corneal diseases such as
astigmatism and late-onset Fuchs' corneal endothelial dystrophy
have yet to be determined. Five stromal dystrophies have
mutations in the keratoepithelin gene. They di~lay marked
phenotypic heterogeneity to the extent that the same mutation
has been described as Avellino corneal dystrophy (ACD) or
granular corneal dystrophy (CDGG 1) in different families.
Conversely CDB 1 and CDB2 are phenotypically very similar but
have been shown to map to two different loci. Similarly
Meesman's corneal dystrophy was thought to be a single gene
defect but it is now known that mutations in either of the keratin
genes, KJ and K12, are responsible. Macular corneal dystrophy
is classified as type I if sulfated keratan sulfate (KS) is absent in
either serum or cornea, or type II if sulfated KS is present in both
cornea and serum. However, mutations or gene rearrangements
within CHST6 have been shown to be responsible for both types.
Recently, it has been shown that mutations in Col8A2 underlie an
early-onset Fuchs' dystrophy phenotype as well as posterior
polymorphous dystrophy. The homeobox PAX6 gene appears to
have a central role in ocular development with mutations
responsible for conditions such as Peter's anomaly, aniridia and
microcornea.
THE CORNEA

EPITHELIAL DYSTROPHIES

subepithelial haze

Fig. 6.16 The commonest corneal dystrophy is epithelial basement membrane dystrophy. This is bilateral, more frequent in women and
its severity increases toward middle age. The clinical signs are variable and there may be grey subepithelial patches (top), dots or microcysts
(middle), and concentric fine whorls of fingerprint lines best seen with retroillumination or broad-beam oblique illumination (bottom). The
term Cogan's dystrophy can be used if large grey dots are the prominent feature. Visual symptoms are uncommon but intensely painful
recurrent erosions may occur following minor trauma. Symptoms are especially common on waking and can be relieved by using artificial
tears during the day and lubricating ointment just before sleep. Severe cases may be helped by debridement of the epithelium, puncture of
Bowman's membrane with a needle or a bandage contact lens. Epithelial debridement followed by superficial excimer laser keratectomy can
be useful in recurrent disease.
 CORNEAL DYSTROPHIES 1

epith elial cyst

"
It
• 4
II- f •
~~... , , . If.';;.
• <1/1' ..
lfl., ~ , "' Fig. 6.17 Histological examination shows thickening and
1";, f II reduplication of the basement membrane and cyst formation .

Fig. 6.18 Meesman's dystrophy is characterized by epithelial

cysts spreading from limbus to limbus. These contain
mucopolysaccharide.

Fig. 6.19 Type I Bowman's

membrane dystrophy (Reis- Buckler's)
predominantly affects Bowman's layer
and the superficial stroma (left). It is
dominantly inherited and has been
linked to the same region of
chromosome 5q31 as granular, lattice,
and Avellino dystrophies. Patients
usually present during the first or
second decade of life with painful
recurrent erosions; subsequent scarring
and surface irregularity blur vision.
Disease is bilateral and symmetrical
with grey reticular opacities seen
mainly in the central cornea.(Right)
Type II Bowman's membrane
dystrophy (Thiel- Benhke dystrophy), a
honeycomb
pattern 1-----+-'n;,+L-~~•
histologically distinct subgroup with a
of anterior honeycomb pattern, has been linked to
opacity in stromal chromosome 10q24. Excimer laser
anterior 1--+------1
opacity superficial keratectomy or lamellar
stroma
keratectomy is the initial treatment of
choice but the disease usually recurs
with time. Penetrating keratoplasty is
rarely indicated.
STROMAL DYSTROPHIES

latti ce lines

margin of
previous 1-H-------'-+-+4!
penetrating
keratoplasty

latti ce

Fig. 6.20 Lattice dystrophy is a common, dominantly inherited, bilateral dystrophy with a varied appearance usually presenting in the
first to second decade of life with blurred vision and recurrent epithelial erosions. The anterior stroma of the central cornea has a pattern of
interlacing, clear, refractile lines and dots (top). Diffuse stromal haze is common in advanced disease. A bandage contact lens or laser
phototherapeutic keratectomy can be used to manage symptoms of recurrent erosion, which are due to accumulated subepithelial amyloid
impairing stromal- epithelial adhesion. Keratoplasty may be necessary by the fourth decade; lamellar keratoplasty is preferable to
penetrating keratoplasty as disease commonly recurs in the transplant so that repeat keratoplasty may .be needed (bottom) . Changes similar
to lattice dystrophy are seen in the corneal degeneration of climatic keratopathy.

Fig. 6.21 Amyloid is deposited in the

anterior stroma and beneath the
epithelium. The lesions stain with
Congo Red and exhibit dichroism and
birefringence when viewed with crossed
polarizing filters. The condition is
amyloid considered a form of localized amyloid
deposits in deposition but the gene defect (5q31 ) is
anterior different from that identified with
stroma systemic forms of amyloidosis. In
Meretoja syndrome (type II lattice
dystrophy) a defect of gelsolin
production (9q34) is associated with
systemic and mild corneal amyloidosis.
 CORNEAL D

Fig. 6.22 Granular dystrophy is dominantly inherited. Different clinical subtypes have been described, although these are identical
ultrastructurally. The condition presents in the first decade of life with white-grey breadcrumb-like or ring patterns in the central anterior
stroma that become more widespread and posterior over time . The intervening stroma is usually clear and the lesions d o n ot involve the
peripheral cornea. Epithelial erosion is uncommon and symptoms are usually limited to glare from light scatter. Symptoms of erosion can
be managed with either a bandage contact lens or laser superficial keratectomy. Rarely, either lamellar or penetrating keratoplasty is
required for visual loss although disease can recur in the donor tissue .

r - - - -- - -- - - - -- - - -_, epit helium

Fig. 6.23 Histologically these amorphous hyaline lesions stain red with Masson trichrome stain. The origin of this material is uncertain.
Patients with Avellino corneal dystrophy demonstrate clinical and pathological changes of both lattice and granular dystrophy.

Fig. 6.24 Macular stromal dystrophy is uncommon and has an autosomal recessive inheritance. Poorly defined grey lesions appear in the
superficial central corneal stroma during the first decade of life; these gradually spread deeper into the stroma and peripherally to the
limbus. The intervening stroma becomes diffusely cloudy with whitish round lesions (macular spots) developing later in the deep stroma.
There is associated corneal thinning. Vision is impaired early and recurrent corneal erosions may occur. Keratoplasty is often required
although the condition may recur in the transplant.
By courtesy of M r M G Falcon.
Fig. 6.25 An abnormal keratan sulphate accumulates intracellularly in keratocytes and extracellularly between stromal lamellae; these
stain Prussian blue with colloidal iron.

corneal arcus

Fig. 6.26 Schnyder's crystalline dystrophy is rare. It is dominantly inherited, bilateral, and often associated with a prominent arcus, as in
this example. Central deposition of crystalline cholesterol esters occurs in the anterior corneal stroma and the condition appears to be a
localized disorder of corneal lipid metabolism associated with hyperlipidaemia. Most cases can be treated by laser superficial keratectomy.
By courtesy of Mr J Kwartz.
 CORNEAL DYSTROPHIES 1

ENDOTHELIAL DYSTROPHIES

stroma oedema

Fig. 6.27 Fuchs' corneal endothelial dystrophy is common. It ranges from a few asymptomatic cornea guttata, which are localized
excrescences of Descemet's membrane in the central cornea best seen by retroillumination (top left), to confluent guttata associated with a
reduced endothelial cell count and corneal oedema. The condition is more frequent and severe in women, and is usually inherited in an
autosomal dominant manner. Its aetiology is unknown. Signs are rarely seen before the age of 50 years (top right). As the disease
progresses, patients notice that vision is blurred on waking but clears during the day. In advanced disease there is pigment granule
deposition on the endothelium, permanent stromal oedema, and epithelial microcysts and bullae. When cysts or bullae rupture they cause
pain, watering and photophobia. Eventually subepithelial fibrosis develops and the eye may become more comfortable (bottom left).
Penetrating keratoplasty may be indicated for pain or reduced vision . Cataract is a common association and the trauma of cataract surgery
can precipitate permanent corneal decompensation. Combined keratoplasty and cataract extraction may be required.
62 THE CORNEA

Fig. 6.29 Histological appearance of a keratoplasty specimen

shows a thickened Descemet's membrane with guttata formation
and loss of endothelial cells.
guttata seen
in relief mode

enla rged
endothelia l cel ls

Fig. 6.28 Specular microscopy of the endothelium from a patient

with m oderately advanced disease shows numerous guttata that
appear as dark areas due to loss of the specular reflection from the
endothelial m osaic over the raised surface of each guttata (compare
with Fig. 6.8).

linear posterior
polymorphous 1---+--+-'..,.-,:;:...:::c.....
dystrophy lesion

Fig. 6.30 Posterior polym orphous dystrophy develops early in life and the changes may be overlooked or noted only coincidentally. There
are geographic 'vesicular' or linear lesions with grey scalloped edges at the level of Descemet's membrane . These changes are only very
slowly progressive and corneal oedema is rare . Filmy peripheral anterior synechiae may be present and secondary glaucoma may develop in
gross cases. Specular microscopy shows decreased endothelial cell density and apparent splits in Descemet's membrane.

CORNEAL ECTASIA
Keratoconus is characterized by thinning and ectasia of the
central cornea. It usually presents during the second or third
decade with slow progression of myopia and irregular
astigmatism. It is bilateral in 95 per cent of cases, often markedly
asymmetrical, and more common in males. Clinical signs include
a characteristic swirling reflex on retinoscopy, distorted mires on
keratometry and inferior steepening of the cornea on topography.
Atopy is the commonest systemic association and the condition
is common in Down's syndrome. Eye rubbing may also have a
role in the pathogenesis. If spectacles do not provide adequate
Fig. 6.32 The abnormally steep corneal apex of keratoconus can be seen on lateral view and may indent the lower lid on downgaze
(Munsen's sign).
By courtesy of Mr K Pullen.
CORNEAL ECTASIA
Fig. 6.31 Transmission electron microscopy shows multilayered
corneal endothelium with the production of epithelial-like cells.
vision the majority of patients can be managed with hard contact
lenses to correct the irregular astigmatism. Only a minority
(10- 20 per cent) with advanced ectasia, an unstable lens fit or
apical scarring require keratoplasty.
Pellucid marginal degeneration is probably a variant of
keratoconus in which the thinning is predominantly in a crescent
adjacent to the inferior limbus. Some patients exhibit thinning
that extends from the centre of the cornea to the inferior limbus,
and thus have features of both conditions. In keratoglobus there
is thinning and ectasia of the whole cornea.
THE CORNEA

I • • • . I SRI: 0. 43 SA!: 1. 67
20 60 PVA: 20/lO - 20; 25
f5 Sim K: 46. 4 x S6 1 43.8 x 176
Min K: 43.7 x !52

Press r1 Key
for HELP

Fig. 6.33 The detection of early keratoconus is vital in patients considering corneal refractive surgery. In the absence of other clinical
signs, pachymetry may show thinning below the visual axis and corneal topography demonstrates steepening below and temporal to the
visual axis. Family members of patients with keratoconus may have subclinical disease detectable only by these methods.

+___,"-+----1 apica I
folds fine verticle
apex of cone
Fleischer f-'---+-'' -" (Vogt's) lines
ring

iron deposit
in epithelium

Fig. 6.34 Fine vertical folds in Descemet's membrane occur near

the apex of the cone (Vogt lines). Iron may be deposited in the
deep epithelium at the base of the cone, best seen using the cobalt
blue filter. This is known as a Fleischer ring; it delineates the area
of corneal ectasia and may be a useful aid when planning surgery.
Histological examination shows iron deposition in the epithelium,
seen as Prussian blue with Perls' stain.
 CORNEAL ECTASIA

Fig. 6.35 Patients with keratoconus can suddenly develop

blurred vision from an acute split in Descemet's membrane results
in a rapid influx of aqueous into the stroma (corneal hydrops) . The
condition is painful but resolves spontaneously over a few months
as endothelial cells cover the defect. Although good vision may
return, scarring often reduces visual acuity.

Fig. 6.36 Pellucid marginal degeneration (left) and keratoglobus (right) are rare variants of corneal ectasia. In pellucid marginal
degeneration there is a zone of maximal thinning adjacent to the inferior limbus. In keratoglobus the entire cornea is ectatic. Management
is more difficult than for keratoconus because of the very irregular shape. If corneal lenses fail, scleral contact lenses or lamellar graft
surgery should be considered.
By courtesy of Mr K Pullen.
THE CORNEA
THE IRIDOCORNEAL ENDOTHELIAL SYNDROME
The iridocorneal endothelial (ICE) syndrome is characterized by
abnormal endothelial cells that appear able to proliferate and
migrate from the posterior corneal surface across the angle and
on to the anterior surface of the iris. Characteristic changes of the
corneal endothelium may be seen with specular microscopy;
these may be focal or diffuse. The syndrome is more common in
women and almost always unilateral. Iris atrophy, ectropion
uveae, pseudo-nodules on the iris and broad-based peripheral
anterior synechiae are common associated changes.
Combinations of these changes have been named as three
variants: essential iris atrophy, the Cogan-Reese syndrome and
Chandler's syndrome (see Ch. 8) although the underlying disease
process is probably the same. Corneal oedema from endoth~lial
failure or secondary glaucoma from outflow obstruction can
cause visual loss. The aetiology is uncertain although herpes
simplex antigen has been identified in the endothelium in some
cases.
ectropion
uveae
Fig. 6.37 This eye has peripheral anterior synechiae superiorly, a
distorted pupil and ectropion uveae caused by the abnormal
endothelial cells proliferating across the angle and producing
traction of the iris.
Fig. 6.38 Endothelial specular photograph from a patient with
subtotal ICE syndrome. The abnormal cells are seen on the right.

CORNEAL EPITHELIAL STEM CELL FAILURE
The corneal epithelium is continuously replaced from a
population of stem cells located at the limbus (see Fig. 6.4).
These cells divide to form daughter cells that move centrally to
replace cells that are lost from the epithelium into the tear film.
If these limbal cells are absent or destroyed the corneal
epithelium is replaced by cells derived from conjunctiva. This
may be accompanied by neovascularization, goblet cells in the
epithelium, blurred vision and an unstable and irregular
CORNEAL EPITHELIAL STEM CELL FAILURE 11
epithelial surface. Congenitally absent limbal stem cells are
thought to underlie the keratopathy of aniridia. Acquired stem
cell failure may follow alkali injury (see Ch. 3), Stevens- Johnson
syndrome or chronic exposure to some contact lens care
products, particularly thiomersal. In severe disease, limbal tissue
can be transplanted either from the fellow eye or a donor eye to
restore a stable corneal surface.
non-wetting
keratinized
epithelium
stromal
neovascu larization
Fig. 6.39 Clinical stem cell failure is seen most frequently after
Stevens-Johnson syndrome, alkali injury and, more rarely, after
surgical excision of the limbus or chronic chemical injury.
Pterygium is thought to be partly the result of focal stem cell
failure following exposure to ultraviolet radiation . This eye shows
an area of conjunctivalization with keratinization of the inferior
cornea in Stevens-Johnson syndrome.
Fig. 6.40 Such eyes can be treated by removal of the abnormal
epithelium and an allograft from the unaffected limbus of the same
or fellow eye to restore normal corneal epithelium.
168 THE CORNEA

Fig. 6.41 This patient had a severe alkali burn with corneal
vascularization and a persistent epithelial defect (top left).
Following a limbal allograft from the fellow eye, the epithelial
defect healed with residual corneal defect (top right). The patient
went on to have a successful penetrating keratoplasty.
By courtesy of Professor Ed Holland.

CORNEAL POST-INFLAMMATORY CHANGES AND DEGENERATIONS

The cornea is susceptible to several degenerative conditions

distinct from age-related degeneration. There may be no
identifiable cause, although chronic inflammation, uveitis and
exposure to ultraviolet radiation may have roles. Most of these
changes are seen in the interpalpebral zone.

Fig. 6.42 In Salzmann's nodular degeneration, elevated lesions

resulting from the replacement of Bowman's layer by hyaline
material are typically distributed circumferentially around the mid
peripheral cornea. The condition is more common in elderly
women and is associated with chronic ocular surface diseases such
as trachoma or severe blepharitis. Focal disease may occur over old
scars. In symptomatic patients the nodules can be removed by
surgical or phototherapeutic keratectomy.
 CORNEAL POST-INFLAMMATORY CHANGES AND DEGENERATIONS 169

Fig. 6.43 Most cases of band keratopathy are idiopathic but the condition may be seen with chronic uveitis, especially in children (see
Ch. 10), following the use of silicone oil for retinal detachment or in phthisis bulbi. A few cases are associated with hypercalcaemia or
hyperphosphataemia with renal failure. Changes begin in the peripheral interpalpebral zone of the cornea as white deposits of calcium at
the level of Bowman's layer with a clear zone separating them' from the limbus. Clear round holes can often be seen in the band
representing the passage of nerves through the deposit. Large aggregated deposits may cause painful epithelial erosions. Treatment by
surgical or laser keratectomy is indicated for patients with pain or impaired acuity.

++--~-__, lipid
~h.L.--t------1 neovascularization

Fig. 6.44 Lipid keratopathy is due to yellow deposition of lipid

and lipoproteins leaking from new vessels in the cornea. It is seen
most commonly following chronic inflammation and
vascularization, such as with herpes zoster keratitis (see Ch. 4) .

Fig. 6.45 Climatic droplet keratopathy (spheroidal degeneration,

Labrador keratopathy) is characterized by translucent spheroidal
deposits appearing in the superficial stroma. The deposits usually
begin at the periphery in the interpalpebral zone. Lesions may
appear adjacent to sites of chronic inflammation but more
commonly they are the result of chronic exposure to sunlight.
70 THE CORNEA
CORNEAL TRAUMA
The corneal epithelium is very susceptible to mechanical injury.
Epithelial abrasions from blunt injury usually rapidly repair,
although a delay in forming permanent hemidesmosome
attachments to the underling stroma can lead to recurrent
epithelial erosion. Epithelial necrosis can also follow hypoxia, or
be secondary to the use of topical drugs, soft contact lens wear
or exposure to ultraviolet radiation (arc eye). The corneal stroma
is resistant to blunt physical trauma but can be penetrated by
sharp objects. The endothelium can be damaged by concussion
injury, intraocular surgery or corneal perforation. Chemical
injuries, particularly with alkali can cause massive and
permanent injury to all layers.
Fig. 6.46 An impacted metallic corneal foreign body is a
common injury associated with drilling or grinding steel without
protective goggles. These particles normally have insufficient
energy to pass through the cornea and so lodge superficially. They
become surrounded by a ring of rust within a few days; this should
be lifted off with a sharp needle or dental burr under topical
anaesthesia to prevent delayed healing.
Fig. 6.47 Corneal blood staining is associated with large
hyphemas, high intraocular pressure and endothelial injury. A dark
brown discoloration from haemoglobin and haemosiderin develops
in the posterior stroma that progresses to involve the full stromal
thickness but leaves the peripheral cornea clear. Blood staining
clears from the periphery and may take years to resolve completely.
It can also occur following intrastromal bleeding from
neovascularization. In this example, the overlying central stroma
has also become necrotic.
By courtesy of Mr M G Falcon.
Fig. 6.48 Striae can be seen following repair of a previous
Descemet's membrane rupture. A common cause is forceps injury
from birth trauma.
 MICROBIAL KERATITIS 1

MICROBIAL KERATITIS

Microbial keratitis presents with pain, photophobia and blurred
vision. It is an ophthalmic emergency as delay in appropriate
treatment can lead to permanent visual impairment or loss of the
eye from corneal perforation or endophthalmitis. Factors that
predispose to corneal infection include contact lens wear,
trauma, surgery or chronic ocular surface disease. An epithelial
defect, stromal infiltration and secondary uveitis or hypopyon
suggest an infectious aetiology.
An accurate bacteriological diagnosis is the key to successful
treatment. Before antibiotic treatment is started the cornea
should be anaesthetized with topical unpreserved anaesthetic
drops and samples are taken for culture (particularly from the
base and edge of the affected cornea) with a scalpel blade or
disposable needle. These samples should be smeared on to a
clean, dry, microscope slide for Gram staining and further
samples placed directly on to blood agar and nutrient broths for
bacterial culture and on Sabouraud's agar for fungal culture. A
history of contact lens wear requires that lenses, their containers
and bottles of care solutions to also be cultured to help identify
the causative organism. An anterior chamber tap is not indicated.
Topical intensive broad-spectrum antibiotic therapy should be
started immediately after cultures have been taken and treatment
modified in due course according to Gram stain, culture and
antibiotic sensitivity findings .
Intensive topical antibiotic treatment is as effective at
delivering therapeutic concentrations of antibiotic as
subcontunctival injection, and oral treatment is indicated only
when there is threatened or actual corneal perforation. Topical
atropine helps to reduce painful miosis. Topical steroids may be
required to suppress inflammation after the infection has been
controlled. Corneal biopsy for histological examination and
culture is sometimes helpful in culture-negative patients not
responding to treatment.
The majority of corneal infections in temperate regions are
the result of bacterial infection. Infections due to fungi or
acanthamoeba are rare in temperate regions but much more
frequent in tropical countries. Most fungi will grow on blood
agar but samples should be plated specifically on to Sabouraud
agar if fungal infection is suspected. Samples for suspected
acanthamoeba infection should be plated on to non-nutrient agar
seeded secondarily with killed Escherichia coli. Viral keratitis is
covered in Chapter 4.

hyperaem ia

st romal infiltrat e

..
'. .. .,. ,-. -..
. .. . ....
I '

..
. .. ' .-
.,__ .. , .. .
. .. Gram-pos itive

·.. ;.c ..
•• •! •• cellular debris
cocci

. ..
-l .
# •

.
-
.·.... ' ...... .lol.\ .. .

Fig. 6.49 Even small corneal infiltrates must be managed aggressively because they can typically progress. Lid and conjunctival
commensals may act as pathogens if the natural defences of the cornea are breached. Gram-positive cocci (blue-black), as seen in this
scrape, are therefore a common cause of microbial keratitis.
 IRE CORNEA

Gram-negative
rods

Fig. 6.50 Soft contact lenses (especially extended wear lenses) predispose the eye to Gram-negative microbial keratitis. Epithelial hypoxia
or other trauma may enable Pseudomonas species to attach to and penetrate the corneal epithelium, rapidly destroy the corneal stroma, and
cause perforation. Gram-negative rods (red) are seen in this corneal scrape.
By courtesy of M Matheson.

Fig. 6.51 Crystalline keratopathy is characteristic of a partially

treated streptococcal keratitis in a patient whose inflammatory
response has been suppressed by steroids. In this case the infection
affects the margin of a corneal graft. The 'crystals' are proliferating
bacteria in natural cleavage planes between stromal lamellae. It is
important not to confuse the filamentary appearance with fungal
keratitis (the filaments are much too large to be fungal hyphae).
By courtesy of Mr M G Falcon.
 MICROBIAL KERATITIS 173

Fig. 6.52 Fungal keratitis is rare in temperate countries but important in tropical countries, often being caused by agricultural ocular
injury. Fungal keratitis may also occur as a secondary infection in chronic ocular surface disease. Many different types of fungi have been
reported to cause ocular infection; the most common are filamentous moulds such as Aspergillus and Fusarium or yeasts such as Candida .
Treatment is with topical antifungal agents; severe infection may require oral treatment. Treatment is often ineffective owing to poor
penetration and progressive disease may require wide surgical excision and keratoplasty. This patient has a pigmented stellate lesion (from
Curvularia species) occurring on a grossly compromised cornea from exposure associated with proptosis from an orbital tumour.

Fig. 6.53 This eye shows secondary infection of a stromal herpes simplex lesion with Fusarium. The satellite lesions .superiorly are
characteristic of fungal infection.
 Fig. 6.54 Histology of the removed corneal button from another eye shows the
filamentary hyphae of Fusarium throughout all levels with destruction of the stromal
lamellae. The hyphae of filamentary fungi have a predilection to spread just anterior to
Descemet's membrane and may be missed at biopsy.

Fig. 6.55 Acanthamoebae are free-living organisms found in tap water; they can encyst when conditions are adverse. They are a rare
cause of microbial keratitis which is usually associated with soft contact lens wear, although in tropical countries it is also commonly caused
by agricultural injury. Early contact lens-associated disease may be limited to the epithelium and is readily curable. Neglected cases with
stromal invasion may develop a ring-shaped abscess around the infected central stroma and hypopyon; amoebae can secrete powerful
collagenases. Eradication is difficult as the amoebae form cysts that are resistant to treatment.
 MICROBIAL KERATITIS

infiltrated nerves
stromal oedema
and infiltrate

fig. 6.56 Disproportionate pain is often a feature, and perineural infiltrates are probably pathognomonic (left) . In vivo confocal
microscopy can provide a quick and definite diagnosis in cases of suspected acanthamoebic keratitis (right). This is the anterior stroma of a
contact lens wearer with a 3-week history of keratitis unresponsive to antibiotic treatment. Note the highly reflective, double-walled, ovoid
structures (1 5- 25 f.Lm) consistent with acanthamoeba cysts (arrows).
By courtesy of Dr T M0ller-Pedersen.

Fig. 6.57 Diagnosis is made by culturing the free-living form

(trophozoites) on E. coli-seeded blood agar medium or by
identifying the organism or its cyst by immunohistochemistry on
an epithelial or stromal biopsy. This photograph demonstrates
acanthamoebic cysts in a biopsy specimen.
176 THE CORNEA

stroma l scarring

'ghost' vessels
//)}~-----1 at level of
endothelium

Fig. 6.58 Interstitial keratitis is believed to result from an immunological response to infectious organisms, and is usually thought of in
the context of congenital syphilis. The active phase of corneal inflammation which is rarely seen in modern ophthalmology presents during
the first two decades of life, with intense photophobia, deep peripheral vascularization (salmon patch) and an anterior uveitis. Treatment
with intensive topical steroids should be started and serological investigation performed. Untreated, the cornea thickens and opacifies,
resolving over several months to leave stromal scarring with the characteristic empty, deep, stromal 'ghost' vessels anterior to Descemet's
membrane.

Fig. 6.59 Patients may have other signs of congenital syphilis

such as neural deafness, Hutchinson's teeth, a collapsed nasal
bridge or intellectual impairment. Patients may also have a
pigmentary retinopathy (see Ch. 10) .
Fig. 6.60 Cogan's syndrome is an autoimmune interstitial
keratitis associated with vertigo and neural deafness that develops
in young adults. It has no relationship to syphilis and the aetiology
is unknown.
 CORNEAL THINNING AND MELTING DISORDERS

--trlc--------1 no stromal haze

Fig. 6.61 Thygeson's superficial punctate keratitis is an uncommon, noncontagious and usually bilateral disease with episodes of
discomfort recurring over several years. The aetiology is unknown, but the rapid response to steroids suggests an immunological basis.
Attempts to identify a viral agent have been unsuccessful. Discrete elevated grey opacities occur in the epithelium without stromal
involvement. There is no associated conjunctival reaction or corneal neovascularization which helps to distinguish this condition from
similar lesions from adenoviral infection or staphylococcal hypersensitivity. Discomfort is usually helped by a short course of topical
steroids although it has been suggested that topical steroids may prolong the course of the disease.

CORNEAL THINNING AND MELTING DISORDERS

Corneal thinning results from uncontrolled lysis of the corneal

release of matrix metalloproteinases (MMPs) and their
stromal matrix. This is usually, but not always, associated with
inhibitors (tissue inhibitors of metalloproteinases; TIMPs) may
inflammation. The precise mechanism of stromal thinning is
lead to lysis of collagen and the proteoglycan ground substance.
uncertain but it has been proposed that imbalance between the
Corneal thinning is also a feature of acne rosacea (see Ch. 4).

Fig. 6.62 Mooren's ulcer is a progressive, painful, idiopathic

ulceration of the peripheral corneal epithelium and stroma of
uncertain aetiology. Recent studies suggest that autoimmunity
against an antigen in corneal stroma is probably triggered by
trauma in genetically susceptible individuals. In tropical regions a
host-parasite interaction may incite autoimmunity. The disease
may be unilateral or bilateral. Bilateral Mooren's ulcer, irrespective
of race or age of onset, is more aggressive; it is rapidly progressive
and responds poorly to treatment. Its onset is heralded by pain,
photophobia and blurred vision as a result of induced astigmatism
and corneal oedema. A peripheral superficial stromal infiltrate
progresses to epithelial ulceration that enlarges centrally and
circumferentially with an undermined edge. Healing leaves an
opaque, vascularized and thinned cornea but perforation, cataract
and glaucoma may also occur. A variety of treatments has been
used including topical and systemic immunosuppression or
excision of the adjacent conjunctiva.
8 THE CORNEA

Fig. 6.63 Peripheral corneal ulceration is often associated with

adjacent scleritis, most commonly due to seropositive rheumatoid
arthritis but also other collagen vascular diseases such as systemic
lupus erythematosus, polyarteritis nodosa, scleroderma, Wegener's
granulomatosis and relapsing polychondritis. Peripheral corneal
melting with minimal overt inflammation may also occur and
progress to perforation. The perforation can be sealed temporarily
with tissue glue and covered with a soft bandage contact lens.
Treatment of any associated systemic disease is essential. An oval
tectonic graft can be performed electively (see also Ch. 5) .

Fig. 6.64 Severe dry eye (keratoconjunctivitis sicca) is a feature

of a minority of patients with rheumatoid arthritis. Such patients
are often severely ill from their systemic disease. Epithelial
breakdown may be followed by a central corneal melt (keratolysis)
and descemetocele formation, with a risk of perforation. The
possibility of coexisting infection must be excluded. The corneal
disease is best managed medically if possible, using punctual
occlusion, intensive lubrication and a soft bandage contact lens.
Tissue glue may be used to close a small perforation. A lamellar
corneal graft may be performed if required, once the epithelial
surface has been stabilized.

~~A=r-----,tFF{'Sirt\:~~~~~~ lipi d deposition

vascularized 1-
periphera l gutter
perforation with
iris prolapse

Fig. 6.65 Terrien's marginal degeneration is seen in either sex and is usually bilateral, although often asymmetrical. It usually begins in
the upper cornea as a faint peripheral stromal opacity with minimal superficial vascularization and slowly progresses to stromal thinning in
an arcuate fashion. The thinned area, which may become ectatic, has a steeper central edge marked by lipid accumulation. Pain is unusual,
although inflammatory episodes may occur. Vision may be affected by induced against the rule astigmatism from vertical flattening of the
cornea in the affected area. Spontaneous perforation may occur, as in this patient, or may be induced by minor trauma . The aetiology is
unknown .

CORNEAL CHANGES FROM METABOLIC DISORDERS AND MEDICATIONS
There are a number of rare metabolic diseases that result in
corneal infiltration with abnormal products. Deposition can
occur in the epithelium, stroma or endothelium. Examples of
these products include mucopolysaccharide (Hurler-Sheie
syndrome), lipoprotein (arcus juvenilis), cholesterol (LCAT
CORNEAL CHANGES FROM METABOLIC DISORDERS AND MEDICATIONS
deficiency), sphingolipid (Fabry's disease), mucolipid, amino
acid (cystinosis), proteins (amyloidosis) and minerals (calcium,
copper). Several drugs that are used to treat systemic conditions
(e.g. amiodarone, chloroquine) are also deposited in the cornea,
usually in the epithelium.
Fig. 6.66 Corneal verticillata are whorled epithelial deposits that
delineate the pattern of epithelial cell migration . They are
commonly seen in patients on treatment with amiodarone or
chloroquine which are deposited in the epithelium. The deposits
are asymptomatic and not an indication to stop therapy. Similar
changes also occur in Fabry's disease, an X-linked sphingolipidosis
caused by a deficiency of the enzyme a-galactosidase associated
with angiokeratomas in the skin.
Fig. 6.67 The mucopolysaccharidoses are lysosomal storage
disorders that are all recessively inherited (except Hunter's
syndrome, which is X-linked). A defect in degrading
mucopolysaccharides (heparan, dermatan or keratan sulfate) leads
to their accumulation and eventual excretion in urine. There are
seven subtypes; corneal clouding is a feature of all except for the
Hunter and Sanfilippo types. Pigmentary retinopathy and optic
atrophy are other features. Corneal clouding is most marked in the
Hurler-Sheie type. The example here is of Scheie syndrome in
which the enzyme a-L-iduronidase is deficient (absence causes the
more severe Hurler's syndrome). Corneal clouding is usually
present at birth and progresses slowly. Keratoplasty may be helpful
if retinal and neurological function has been preserved but,
unfortunately, the clouding tends to recur in the graft. Other
features are claw hands with stiff joints and a characteristic facies,
but the severe neurological and cardiological features of Hurler's
syndrome are absent. Corneal clouding reduces in some patients
after successful bone marrow transplantation.
180 THE CORNEA

stromal haze

Fig. 6.68 Lecithin- cholesterol acyltransferase (LCAT) deficiency, Tangier disease and fish eye disease are autosomal recessive disorders
of lipid metabolism (dyslipoproteinaemias). LCAT deficiency presents with early onset of a marked arcus and diffuse fine grey dots
throughout the stroma that progress centrally from the periphery. Vision is usually preserved. This patient had acuity of 20/20 with the left
eye; the right eye had been grafted 10 years previously and remained clear.

Fig. 6.69 Crystalline corneal deposits seen as grey or golden dots

in the central cornea occur in cystinosis, oxalosis, gout and gold
therapy for rheumatoid arthritis, as well as in Schnyder's and
Bietti's dystrophies.
By courtesy of Mr M G Falcon.
Fig. 6.70 Deposition of copper in Descemet's membrane (Kayser-Fleischer ring) occurs in Wilson's disease (hepatolenticular
degeneration) from a deficiency of the transport protein caeruloplasmin in the blood with defective excretion of copper by the liver
lysosomes. Patients develop liver failure and later neurological problems from deposition of copper in the basal ganglia . The
Kayser- Fleischer ring is a peripheral orange, brown or green-brown discoloration at the level of Descemet's membrane adjacent to the
limbus. It is often better visualized with gonioscopy and is present in virtually all patients with neurological manifestations ofWilson's
disease, but may be absent in early cases.
By courtesy of Mr J Jagger.

Fig. 6.71 Crystalline deposits are seen rarely in some patients

with monoclonal gammopathy associated with multiple myeloma
or lymphoma. The deposits can occur at any level in the stroma
and may be intracellular or extracellular.
182 THE CORNEA

REFRACTIVE SURGERY

Refractive corneal surgery alters the radius of curvature and
hence the dioptric power of the anterior corneal surface, the
most powerful refracting element of the eye. This can be achieved
by an ever-increasing range of sophisticated techniques which
include excimer laser ablation, relaxing incisions (radial
keratotomy, limbal astigmatic keratotomy), tissue shrinkage
(thermokeratoplasty) and corneal inlays. Indications are primary
refractive errors or surgically induced errors following cataract
surgery or keratoplasty. Excimer lasers contain a mixture of
argon and fluorine gases and emit ultraviolet light at a
wavelength of 193 nm . This radiation has very low penetration in
water but each photon has sufficient energy to break the
hydrocarbon bonds of the corneal stroma. By controlling the
distribution of energy it is possible to remove very precisely small
amounts of tissue to alter the radius of curvature of the corneal
surface, thereby correcting myopia, astigmatism, hyperopia and
higher-order optical aberrations (irregular astigmatism) . The
degree of laser refractive correction is limited by the amount of
tissue that can be ablated; a residual corneal bed of less than 250
!liD risks eventual corneal ectasia. The present limitations for safe
treatment are generally considered to be less than 8- 1Od myopia,
Sd ·hyperopia and 4d astigmatism. Treatment of the anterior
corneal surface after debridement of the epithelium is known as
photorefractive keratectomy (PRK.); the same treatment when
placed under a flap of corneal stroma cut with a m icrokeratome
is called laser-assisted intrastromal keratomileusis (LASIK) and
removal and replacement of the epithelium following ablation is
known as LASEK. The precise indications for each technique are
still a matter of discussion. A superficial keratectomy performed
with the laser to remove diseased tissue is known as
phototherapeutic keratectomy (PTK).

Fig. 6.72 Radial keratotomy relies on relaxing incisions that produce

peripheral corneal ectasia to flatten the optical zone. Overall short-term results
are good but there is a small risk of perforation or microbial keratitis following
the procedure. Long-term complications include fluctuating myopia, haloes
from incisions lying in the optical zone, a gradual hyperopic shift over several
years, and increased risk of rupture from trauma from a weaker cornea. The
procedure has generally been replaced by laser surgery.
By courtesy of Mr W Jory.

90 90
12 0
• • • • • 60 120
• • !i • • 60

•
• • •
• • •
150
• • 30
• 30
• • •
• • •
• • •
0 180 0
180
• ••
• • •
• • •
2 10 • •330 •330
• • •
• • •
• • • •300 •300
2 40
• • •
Fig. 6.73 Topography performed before and after laser refractive
surgery for the correction of myopia and with the rule astigmatism
47.50 46.50 45.50 44.50 43.50 42.50 41.50 40.50 39.50 38.50 3 7 .50
shows that the radius of the anterior surface of the cornea has been
flattened centrally and the astigmatism removed to leave a
spherical anterior cornea surface.

folds in flap
after LASIK
Fig. 6.75 Stromal scarring is not a feature after LASIK.
Complications are due to incorrect positioning or calibration of the
laser; flap-related problems (buttonholes, partial, free or irregular
flaps) can result from defective microkeratomes or poor technique .
Wrinkles or folds can sometimes be seen after the flap has been
replaced; these may be visually significant.
Fig. 6.74 Following photorefractive keratectomy (PRK) there is a
risk of superficial stromal scarring that is seen as a central anterior
stromal reticulated opacity on slit-lamp examination; this usually
resolves over several months. Regression of myopia can occur
following epithelial healing and regeneration. In general with PRK,
the greater the refractive correction the greater the risk of stromal
haze and the less predictable the refractive outcome.
Fig. 6.76 A diffuse lamellar keratitis at the interface can be
sometimes seen within days to weeks after treatment and is caused
by debris from instruments or bacterial toxins. Treatment is with
topical steroids; sometimes the flap requires lifting for irrigation
and mechanical debridement.
Fig. 6.77 Complications are rare but can be very serious. In this
instance a small infiltrate has developed under the flap 3 days after
surgery. Fusarium was subsequently isolated.
CORNEAL TRANSPLANTATION AND REJECTION
Corneal transplantation may be indicated for visual, therapeutic
or tectonic reasons (i.e. repair of perforation or ectasia). Visual
indications include the correction of the irregular astigmatism of
keratoconus or the removal of corneal opacity from scarring.
Therapeutic indications include the relief of pain from bullous
corneal oedema or the removal of infected tissue in fungal
keratitis. A tectonic transplant may be required to restore the
integrity of the eye when there is a large corneal perforation. A
Fig. 6.78 Epithelial cells may be implanted under the flap or
grow under the edge. These can cause astigmatism or even flap
melting. Progressive ingrowth requires removal by relifting the flap.
transplant may be either full thickness (penetrating keratoplasty)
or partial thickness (lamellar keratoplasty) in which the
endothelium and posterior stroma are preserved . As the
endothelium is the primary target for autograft rejection which
can lead to transplant failure, a lamellar transplant is potentially
advantageous as rejection episodes are less severe and do not lead
to transplant failure. However, the visual results are not usually
so good as a result of interface irregularity.
epithelial
~------1 rejection line
margin of graft
~-l-~--L------~~
Fig. 6.79 Epithelial rejection appears as a line of raised epithelial
and inflammatory cells that often originate from a focus of
inflammation such as a loose suture. It is readily reversed with
topical steroids and has no long-term effects.
 REFRACTIVE SURGERY

Fig. 6.80 Stromal rejection appears as diffuse dots in the

superficial stroma. This can resemble infectious (especially
adenovirus) keratitis. It is limited to the donor button.

stromal rejection line

oedema
graft sutures

stromal oedema

Fig. 6.81 Endothelial rejection is seen as a discrete line of

lymphocytes (Khodadoust line) on the corneal endothelium
radiating out from the interface between transplant and host. In
the affected area there is localized corneal oedema and KP's on the
endothelial surface.
Primary Glaucoma
David Garway-Heath, Paul Foster, Roger Hitchings

Classification of Glaucoma
Intraocular Pressure
Aqueous Humour Formation and Outflow
Primary Open Angle Glaucoma
Primary Angle Closure
Primary Angle Closure Glaucoma
Congenital and Developmental Glaucoma
8 PRIMARY GLAUCOMA

CLASSIFICATION OF GLAUCOMA

Glaucoma is a term used to describe a group of conditions that
share a chronic progressive optic neuropathy. Glaucomatous
optic neuropathy is characterized by structural changes in the
optic nerve head in which the neural rim is thinned and the cup
enlarged; there is usually corresponding visual field loss and
raised intraocular pressure (lOP).
Glaucoma may be classified as primary when the cause of the
disease is unknown, or secondary when an increase in lOP occurs
secondary to another ocular disease. Primary glaucomas may be
further subdivided, as shown in Table 7 .1.
The term 'ocular hypertension' describes an eye that has an
lOP above the normal range with a normal visual field, optic disc
and retinal nerve fibre layer; normal pressure (or low tension)
glaucoma describes an eye with primary glaucoma and open
angles but with an lOP in the normal range. Primary open angle
glaucoma (POAG) is considered in most detail as it is the most
prevalent form of glaucoma. Much of the information, however,
is relevant to all three groups.

Table 7.1 Primary glaucomas

Primary open angle glaucomas
Primary open angle glaucoma
Normal pressure glaucoma
Primary juvenile glaucoma
Primary angle closure glaucomas
Acute angle closu re glaucoma
Intermittent angle closure glaucoma
Chronic angle closure glaucoma
Primary congenital glaucomas
Primary congenital glaucoma
Primary infantile glaucoma
Glaucoma associated with congenital anomal ies

INTRAOCULAR PRESSURE

The concept of ' normal' lOP is based on a population survey in
Europe where readings were assumed to be normally distributed
and two standard deviations above the mean gave a normal upper
limit of 21 mmHg, implying that only 2.5% of normal people
would be expected to have 'increased' lOP. However, 'normal'
lOP is not normally distributed but skewed to the right and as a
result a greater proportion of the normal population has an lOP
exceeding 21 mm Hg than was predicted initially. This right skew
increases with age and varies by race; for example, mean lOP in
Japan is 11.6 mm Hg but that in Barbados is 18.1 mm Hg. lOP
tends to be higher in older people. Measurement of lOP by
methods that applanate the cornea (see Ch. 1) is affected by
central corneal thickness which varies between people. The
Goldmann applanation tonometer assumes a central corneal
thickness of 520 11m; applanation underestimates lOP with
thinner corneas and overestimates lOP with thicker corneas. As
a rule increased corneal thickness of 10 11m artefactually
increases the lOP by 1 mm and similarly underestimates lOP in
thin corneas. This is of considerable importance after laser
corneal refractive surgery. The factors that regulate lOP are those
that alter the rate of aqueous production or outflow resistance.

Ocular hypertension b:J

100 Normal pressure glaucoma D
Glaucoma D

~
<1l
v
"'en 10
0
;::::;.
"'
'-
Q)
..0 Fig. 7 .1 In a population survey of 2000 Caucasian males aged
E over 40 years, the normal mean lOP was found to be 16.0mmHg
:::>
z with a standard deviation of 2.5 mm Hg. Two standard deviations
from the mean is 21 mm Hg, which is usually regarded as the
(statistical) upper limit for normal lOP; however, the distribution is
skewed with a longer tail to the right, and most of these people
0 +--.--.--,--.-~--,--,---,--,--,--,--,~
7 9 11 13 15 17 19 21 23 25 27 29 31 33
have ocular hypertension. Glaucoma patients with an lOP lower
than 2 1 mm Hg are regarded as having normal pressure glaucoma;
Pressure (mm Hg)
above this level they have either ocular hypertension or glaucoma.
 AQUEOUS HUMOUR FORMATION AND OUTFLOW

25
- Sitting - Supine

20

Fig. 7.2 Diurnal pressure curves show that

o, 15
I lOP is dependent on posture and time of
E day. lOP is always higher when supine in
5 comparison to an erect posture. This graph
Q.

Q 10 shows that during the day lOP is always

lower when erect than when supine. (Night
time measurements of lOP were only taken
in the supine position) . lOP tends to be
higher in the mornings than later in the day.
Light I Wake Dark Light I Wake lOP also varies seasonally, being slightly
0 +---,----,----,---,----,----,----,----,---,----,----,---4 higher in winter. Whatever the mechanisms
15.30 17.30 19.30 21.30 23.30 01.30 03.30 05.30 07.30 09.30 11.30 13.30 regulating lOP the end result is that the two
Time of day I night eyes of an individual usually have a similar
lOP.

55
o,
I
E
45
5
~
~
OJ 35
a.
~
Fig. 7.3 Variation in lOP during the day is often exaggerated in
"' patients with POAG, clearly illustrated by the 2-hourly pressure
::l
u
0
25 readings of the right eye of this patient. Note the 'normal' levels
~ from 17.00 to 19.00 hours and the rapid pressure rise between
+'
!: 19.00 and 21.00 hours. It is obviously necessary to have frequent
15
lOP measurements to manage patients with disease progression
5 7 9 11 13 15 17 19 21 23
despite 'controlled' lOP. Glaucoma surgery significantly dampens
am Time (hours) pm
diurnal curves.

AQUEOUS HUMOUR FORMATION AND OUTFLOW

Aqueous humour forms at a rate of 2-3~-tllmin during the day,
the fluid volume of the anterior chamber being exchanged every
lOOmin. At night aqueous flow is approximately halved. Aqueous
is formed by a combination of active and passive processes
(diffusion and ultrafiltration). About 70 per cent of aqueous is
actively secreted by the nonpigmented ciliary epithelium; sodium
transport is crucial for this process. Although the ciliary
epithelium itself does not have a neuronal supply blood vessels in
the ciliary body are well endowed with sympathetic fibres
through which drugs such as the sympathomimetics and
P-blockers probably act. The mechanisms controlling aqueous
secretion remain incompletely understood. There is no evidence,
however, that the rate of aqueous production is increased in
patients with POAG.
There are two routes of aqueous outflow: trabecular
meshwork (conventional) and uveoscleral (nonconventional). Up
to 90 per cent of aqueous outflow is through the trabecular
meshwork and into Schlemm's canal and the aqueous veins and
is dependent on pressure. Increased resistance to outflow,
because of age or disease, requires a higher 'head' of pressure to
maintain the same throughput of fluid out of the eye resulting in
a higher lOP. At least 50 per cent of resistance to outflow is
located in the juxta canalicular region of the trabecular meshwork
and in POAG resistance to outflow in this region is thought to be
abnormally high. Approximately 10 per cent of aqueous outflow
is through the uveoscleral pathway although recent studies have
suggested that outflow here may actually be much higher in the
young. Aqueous flows through the interstitial spaces of the ciliary
muscle into the supraciliary and suprachoroidal spaces and
finally through the sclera or into the vortex veins. Uveoscleral
flow is independent of pressure and decreases with age.
PRIMARY GLAUcoMA

Lens
Cornea - - - - - - - - ,
Trabecular meshwork --------..
Cana l of Schlem m - - - - ,
Fig. 7.4 Aqueous is secreted by the ciliary epithelium and flows
past the equator of the lens through the posterior chamber and the
Collecting c h a n nels ------.-~~ /A--:::;~ pupil to reach the anterior chamber. Aqueous !; aves the anterior
Iris - - - --7"-'----f.f.;=::... chamber and enters the canal of Schlemm by the trabecular
Ciliary body -----7L__----.fr.?L--~ meshwork. It then passes into collector channels and aqueous veins
to reach the episcleral veins. Resistance to flow is greatest at the
Sci era - --t'----
trabecular meshwork. A proportion of aqueous also leaves the eye
Suprachoroidal space --,'-------,t"'l by draining into the suprachoroidal space and is known as the
uveoscleral or nonconventional outflow pathway.

li mbus

Fig. 7.5 Aqueous humour passes through the canal of Schlemm

to drain into collector channels (in the sclera) which empty into
the conjunctival veins . This anastomosis can be seen as 'aqueous'
veins in the conjunctiva.

Schlemm's canal --+'-+-o-A.----__/

Fig. 7.6 The trabecular meshwork has an inner lamella ted and
Scleral spur -t'+f+->L..f-H'-,--1/.
an outer nonlamellated cribriform (juxtacanalicular) region. The
lamellated meshwork is further divided into a uveal portion
(between scleral spur and iris root) and a corneoscleral portion
(between cornea and scleral spur). The lamellated region is made
up of connective tissue plates with a core of elastic and collagen
fibres covered by trabecular cells. The juxtacanalicular region has
Ciliary muscle Uveal TM Iris no collagen beams and consists of an elastic network and layers of
cells (cribriform cells) within an extracellular matrix. The ciliary
Ci liary process
muscle tendon inserts into the inner meshwork and scleral spur.
 Fig. 7.7 The corresponding angle anatomy can be seen in this
histological section.

Table 7.2 lists the factors that potentially cause an increase in Table 7.3 shows factors that may cause a decrease in lOP:
lOP; these include increased ciliary epithelial production of decreased aqueous production, structural alterations in the
aqueous, an altered blood- retinal barrier and, more commonly, conventional outflow channels, and an increase in outflow by
increased resistance of the conventional outflow channels. nonconventional routes.

Factors that may cause an increase in lOP

Increased fluid load Pretrabecular block Trabecular block Post-trabecular block

Increased blood flow to ciliary body Peripheral anterior synechiae Mechanical (e .g. silting of Caroticocavernous fistula
Adrenergic (~/~ 2 ) agon ists (e.g. salbutamol) Rubeotic membrane meshwork with debris or causing raised episcleral
Dopamine (D 1) agonists (e.g. ipopamine) pigment) venous pressure
Prostaglandins (e.g. Posner-Schlossmann Pharmacological (e.g.
syndrome, postoperative pressure rise) corticosteroid response)
Nitric oxide (e.g . uveitis)

Factors that may cause a decrease in lOP

Decreased aqueous formation Decreased resistance to conventional outflow Increased nonconventional outflow
Reduced blood flow to ci liary body Drugs: cx2 agonists
Dehydration Pilocarpine Prostaglandin and prostamide analogues
Destruction of cil iary body (disease ~ 2 agonists Deep sclerectomy or viscocanalostomy
or therapeu tic) ex, agonists Ciliary effusion
Drugs: Prostamide analogues Rhegmatogenous retinal detachment
~ 2 blockers Mechanical:
a,fa2 agon ists Laser trabeculoplasty
Carbonic anhydrase inhibitors Trabeculectomy
Cardiac glycosides Deep sclerectomy or viscocanalostomy
92 PRIMARY GLAUCOMA
PRIMARY OPEN ANGLE GLAUCOMA
PREVALENCE
POAG, or chronic simple glaucoma, is the most common form
of glaucoma in the West. The median age-adjusted prevalence in
people aged over 40 years taken from a number of population
surveys is 1.6 per cent in Caucasians and 4.6 per cent in black
people. Approximately 4 per cent of white people and 8 per cent
of black people with glaucoma are bilaterally blind. Typically the
onset is insidious and central visual acuity is not lost until the late
stages of the disease. Most referrals follow opportumsnc
screening of the asymptomatic patient; alternatively patients
present when both eyes become affected or coincidentally when
the patient accidentally covers the 'good' eye and becomes aware
of severe visual loss in the affected eye.
Considerable emphasis has been placed on screening the
asymptomatic population as there is evidence that early
treatment of the disease carries a better prognosis. The low
overall prevalence of the disease means, however, that mass
population screening is uneconomic and screening has to be
restricted to higher risk groups. The major risk factors for
glaucoma are raised lOP, older age and ethnic origin. Other risk
factors include a positive family history, myopia, vascular
disorders (systemic hypertension, nocturnal hypotension and
vasospasm) and possibly diabetes. There is a continuous,
exponential relationship between the level of lOP and risk of
glaucoma. The prevalence of POAG also increases exponentially
with age. Around 1 per cent of Caucasians aged 50 years have
POAG, rising to 4 per cent in those aged 80 years. For black
people, the respective values are 3 and 13 per cent.
Familial and genetic factors have been implicated in
susceptibility to glaucoma but the mechanisms that lead to the
development of glaucoma are not yet known. In some families
Fig. 7.8 (Left) Scanning electron micrograph showing an en face view of the normal meshwork from the anterior chamber.
(Right) Transmission electron micrograph showing details of the meshwork bordering Schlemm's canal (SC)in a normal eye. Aqueous
enters the canal as a result of the formation of giant vacuoles (GV) that rupture into the canal.
Reproduced with permission from Johnson J Glaucoma 2001) pp 55-67.
the pattern of inheritance is autosomal dominant with reduced
penetrance. The role of genes is complex; susceptibility is
probably under multigenic influence and disease may not
manifest without the presence of other risk faci:ors. At present
identified glaucoma genes account for fewer than 5 per cent of
cases of primary glaucoma. The first glaucoma gene to be
identified was the MYOCITIGR gene which codes for the protein
myocillin found in the trabecular meshwork and also in the
ciliary body, retina and optic nerve head. Steroids induce the
expression of myocilin in the trabecular meshwork. Other gene
mutations and polymorphisms have been reported. For example,
OPTN, which codes for a protein thought to be involved in the
tumour necrosis factor (TNF) signalling pathway and OPAl,
which codes for a dynamin guanosine triphosphatase involved in
forming and maintaining the mitochondrial network have been
implicated in normal-pressure glaucoma; GSTMJ, which codes
for glutathione S-transferase, may be associated with POAG.
PATHOGENESIS OF GLAUCOMA
Trabecular meshwork
In POAG with elevated lOP there is increased outflow resistance
and reduced outflow facility. Factors that may contribute to this
include an abnormal amount or composition of extracellular
matrix, plaque-like deposits in the juxtacanalicular meshwork,
changes in trabecular meshwork endothelial cells and in the
cytoskeleton of trabecular cells, accelerated trabecular cell death
and collapse of trabecular beams.

Optic nerve damage
Loss of visual function in glaucoma results from retinal ganglion
cell damage and death. There is some evidence that larger
ganglion cell axons may be more susceptible to injury than small
axons, although this is controversial. Ganglion cells with larger
fibres subserve the functions of movement detection and contrast
sensitivity (magnocellular pathway) and blue- yellow colour
vision (koniocellular pathway). Those with small diameter fibres
are responsible for acuity and red- green colour sense
(parvocellular pathway). Tests that detect loss of contrast
sensitivity, movement thresholds and blue- yellow colour vision
are promising tools for earlier diagnosis.
The mechanisms underlying neuronal damage are still not
fully elucidated and include mechanical deformation, vascular
insufficiency and neurotoxic injury. These processes are not
mutually exclusive and the final common pathway is thought to
be ganglion cell apoptosis (cell death without inflammation).
Mechanical damage from raised lOP may be mediated in a
number of ways. High pressure will distort the plates of the
lamina cribrosa, compressing ganglion cell axons and blocking
retrograde flow of neurotrophic factors to the ganglion cell body.
Distortion of lamina plates may also disrupt capillaries that lie
within the plates. Astrocytes, which provide physiological and
peripapillary
crib rosa
Fig. 7.9 Histological sections of normal disc (left) and cupped disc (right).
PRI
structural support to ganglion cell axons and maintain the
trabecular beams of the lamina cribrosa, may become
dysfunctional resulting in disrupted axoplasmic transport, direct
neurotoxicity (e.g. from nitric oxide orTNFa), and disruption of
the extracellular matrix and cribosal plate architecture. The
trabeculae of the lamina cribrosa are at the site of maximum
mechanical stress in the eye. This is greater when the sclera is
thinner, when the optic disc is larger (e.g. in highly myopic eyes),
and at the vertical poles of the disc. Theoretically collagen or
elastin may be structurally abnormal in some eyes making them
more susceptible to lOP damage than others.
A vascular mechanism may have several components relating
to systemic blood pressure (BP), local vascular damage and
autoregulation. The concept of 'perfusion pressure' (mean BP
minus lOP) is important in describing the potential effect of
either raised lOP or low BP, particularly in the nocturnal
hypotension that affects some patients. A primary vessel defect or
poor autoregulation involving the short posterior ciliary arteries
and the circle of Zinn-Haller that supply the laminar region (see
Ch. 17) could cause local vascular insufficiency. Vascular
insufficiency may directly damage neurones through ischaemia,
hypoxia, or indirectly by activation of astrocytes.
 larger pores

Fig. 7.10 A coronal digest preparation demonstrates the pores in the lamina
cribrosa through which the retinal axons pass. The pores have a larger diameter with
less supporting collagenous tissue superiorly and inferiorly; this is the area in which
glaucomatous visual field damage initially occurs.
Reproduced from Arch Ophthalmol1990; 108:51- 143.

cribriform plate

neuroretinal rim
cribriform plate
superficial pores

central retinal
diplaced posteriorly
blood vessel

Fig. 7.11 Laminar digests illustrating posterior displacement of the lamina cribrosa with glaucomatous damage: (top left) normal adult;
(bottom left) moderately severe glaucoma; (bottom right) end stage glaucoma.
Reproduced with permission of the Editor, Arch Ophthalmol.
 PRIMARY OPEN ANGLE GLAUCOMA 15

ASSESSMENT OF THE EYE WITH PRIMARY OPEN ANGLE GLAUCOMA

Key components for assessment of the glaucomatous eye are: techniques of lOP measurement and gonioscopy are covered in
lOP measurement, gonioscopy, examination of the optic disc and Ch. 1.
retinal nerve fibre layer and visual field examination. The

Gonioscopy

In addition to the 'openness' of the angle, the profile of the iris
approach to the angle should be noted, the amount and
distribution of pigment in the angle and, if present, the extent of
peripheral anterior synechiae. Spaeth's grading describes the iris
profile as steep, regular or concave, or as having a plateau
configuration (anterior chamber deep centrally but shallow
peripherally with a prominent peripheral roll of iris seen on
indentation gonioscopy). In heavily pigmented eyes the
peripheral iris may be particularly bulky and a cause of angle
crowding and closure.
Table 7.4 describes angle grading, derived from Scheie and
Shaffer.

Table 7.4 Angle grading (derived from Scheie and Shaffer)

Angle grade Angl e width Descript ion
4 35-45° Wide open
3 20-35° Open
2 20° Apex of ang le not visi ble, scl era l spu r visible
1 1QO Posterior half of meshwork not visib le, spur not visible, Schwalbe's line visible
0 oo No ang le structures seen

Normal Angle closure

Trabecular Schwalbe's Angle Collecting

meshwork line Cornea closure channels

Fig. 7.12 Different systems of grading 'openness' of the angle

have been suggested. In clinical practice it is necessary to know
whether: (i) the angle is open and incapable of closure; (ii) the
angle is open, but could potentially close (i.e. is narrow); (iii) the
angle is closed; and (iv) if peripheral anterior synechiae (PAS) are
present in part or throughout. This composite diagram correlates
the gonioscopic and microscopic appearances of the angle of the
anterior chamber when both 'open' and 'closed' and shows the
relationship of the trabecular meshwork to the surrounding cornea,
Ciliary band Lens Canal of Sch lemm
ciliary body and canal of Schlemm

Schwalbe's line

mid-trabecular
ci liary band pigmentary
(iris root) band

Fig. 7.13 A goniophotograph of the angle of the anterior chamber in a patient with pigmentary glaucoma shows extensive pigment
deposition at the trabecular meshwork so that the angle details are more clearly visible. The trabecular meshwork extends from the anterior
pigment deposition (uppermost in this picture) to the ciliary band (anterior iris root). There is a sharply defined midtrabecular band of
pigment.
 PRIMARY GlAUCOMA
Optic disc
The recognition of glaucomatous cupping is fundamental to a
diagnosis of POAG. The normal appearance of the optic disc is
governed by the size and shape of the optic nerve and by the
angle it makes with the eye (disc tilt). Larger discs have larger
physiological cups and the cup is more elliptical in elliptical discs .
The optic disc is best examined by stereo-ophthalmoscopy with
small central cu p
a high-power biconvex lens. Red-free photographs show retinal
nerve fibre detail more clearly. As with any chronic disease
producing gradual change, a transition phase occurs between the
optic disc appearing merely ' suspicious' to 'typically
glaucomatous'.
Fig. 7.14 Both optic discs of this patient are normal, being
symmetrical in appearance with similar overall dimensions, shape,
colour and contour and having a clearly visible and full retinal
nerve fibre layer. A small physiological cup of about 0.2 vertical
ratio is present in each optic disc.
norm al neuro ret ina l
rim
pores in
large central cup cribrifo rm pl at e
Fig. 7.15 The physiological cup varies in size from patient to
patient and is dependent on the overall dimensions of the scleral
canal; eyes with large scleral canals tend to have larger discs and
larger cups. In this patient, the optic discs and cups are large but
normal and the physiological shape of the rim is maintained. The
two eyes of this individual are symmetrical (cup : disc ratio
difference < 0.2), the neuroretinal rim is pink and the retinal nerve
fibre layer is intact.
 PRIMARY OPEN ANGLE GLAUCOMA 197

superotemporally

scle ral crescent

Fig. 7.16 When the disc is tilted, the neuroretinal rim is broader and slopes gently in the direction of tilt and is thinner and more sharply
defined opposite this. The most common direction of tilt is in the inferotemporal direction. (Left) A gentle superotemporal tilt; (centre) a
temporal tilt with the gentle slope temporally and a temporal 'scleral crescent' that is typical in myopic eyes; and (right) a nasal tilt in which
the rim appears thinner and more sharply defined throughout the circumference of the disc. These are all normal variants.

striations in
--,'-,'-,-..,.--1 retinal nerve
f ibre layer

pale and thin

neuroretinal rim
pink
neu roretinal rim defect in
retinal nerve
'------":.L..__ ...L.l_ _j "-.L.L.<'----..l..'tl~'-.lc-'-"-_J fibre layer

Fig. 7.17 Although the right optic disc of this patient is normal, the left shows evidence of glaucomatous change. A comparison of the
two discs reveals that the optic cup in the left eye is vertically elongated; there is loss of the neuroretinal rim at the 5 o'clock position; and
pallor of the rim in the inferotemporal quadrant. Visibilty of the retinal nerve fibre layer is less clear adjacent to the deficient neuroretinal
rim and here the retina is darker. Unless the disc is tilted, or has an unusual shape, the neuroretinal rim is usually thickest in the
Inferotemporal part of the disc, followed by the Superotemporal, then the Nasal and then the Temporal part (the 'ISNT rule'). Acquired
change secondary to chronic glaucoma is suggested by asymmetry between the two optic discs and thinning of the neuroretinal rim so that
the physiological shape of the rim is lost.
PRIMARY GLAUCOMA

Fig. 7.18 Thinning of the neuroretinal rim is defined by contour, not by colour. The thinning may be diffuse, focal or a combination of
the two. The remaining neuroretinal rim usually maintains its colour. (Left) The inferotemporal rim is thinner than the nasal rim so that the
physiological shape (IS NT rule) of the rim is lost. (Middle) Focal thinning of the rim has caused a 'notch'. (Right) Diffuse thinning of the
rim and focal thinning at the inferior pole is associated with a retinal nerve fibre layer defect. Small optic discs with very shallow cups
develop 'saucerized cupping' when neuroretinal tissue is lost: the central depression maintains its colour and damage is easily missed unless
the contour of the disc is examined stereoscopically. Peripapillary atrophy is associated with glaucomatous optic neuropathy and may
enlarge as the disease progresses.

neuroretin al rim
edge of cup r---~~;;.:.:.:::::...p:.H-~F

Fig. 7.19 Advanced glaucomatous cupping in the right eye.

There is a marked enlargement of the cup, together with extreme
attenuation of the neuroretinal rim and undermining of its margin.
The cribriform plate is exposed and bowed posteriorly. The
cup : disc ratio is almost 100 per cent.
 PRIMARY OPEN ANGLE GLAUCOMA 199

zone ~ parapapilllary !=_:_~

atrophy
zone a parapapilllary
atrophy

Fig. 7.20 This disc shows an unusually large superotemporal

splinter haemorrhage. The inferotemporal quadrant of the
neuroretinal rim is the most frequent site of sphincter
haemorrhage. Disc haemorrhages are more common in patients
with normal tension glaucoma. Recurrent haemorrhages are not
uncommon and may be followed by field defects.

Fig. 7.21 Red-free photography demonstrates the retinal nerve fibre layer more clearly than conventional colour photography (top) . An
intact nerve fibre is seen in. With glaucoma, nerve fibre loss may be diffuse (the nerve fibre layer becomes less visible), focal (wedge-shaped
defects) or combined. Nerve fibre loss is best seen adjacent to the poles of the optic disc where nerve fibre striations are usually most
prominent. In this patient focal wedge-shaped defects extend to the optic disc margin.

Imaging technologies

Several instruments utilizing different optical principles have
been introduced over the past 15 years to record anatomical
changes in the nerve fibre layer and optic disc for objective
diagnosis and to monitor progression; the role of these in clinical
practice has still to be established. The devices include digital
stereoscopic cameras and scanning devices, scanning laser
tomography, scanning laser polarimetry, optical coherence
tomography and retinal thickness analysis. Measurements can be
compared with normal ranges although the overlap between
normal and glaucomatous values makes diagnosis on this basis
difficult, and the devices may be more useful for detecting
progressive structural change in an individual eye.
PRIMARY GLAUCOMA

Sept 1992 Jan 1994 June 1995 June 1998

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J.. J.'- ::::::::::: :::::::::::::::~::r:-:~::r:~.::f'i:~~::~::::7=:!! :~~~4 ~:::r:::: "l ·~lljf

~
~ ::::::::::: ::::::::::: : :: :~ :: ~ ::: :::::: :::i:::: :f:::: :F: :::::::::::::::: :::::: ::: ::: ::::: :~ ::::::
-I I 0 t I 0 0 I 0

1.~ I:T- · .'OC 1:99 · .(( ·::I

Fig. 7.22 The right eye of a 62-year-old man with ocular hypertension who was followed for 7 years. Optic disc photography shows
subtle thinning of the superior rim and changes in the kink of the inferior temporal vein over this time period indicating minor tissue loss
in these areas. Images taken with the Heidelberg scanning laser ophthalmoscope illustrate the change in the rim area (green and blue
shading) over this time. Surface height changes are shown in the third row (red indicates significant depression, green elevation) and the
visual field changes are shown in the fourth row. These show subtle visual loss 6 years later. Numerical values for rim area are plotted
against time. Note that optic disc changes are visible before visual field loss.
Visual function several fields over many months is normally required before
progression can be diagnosed with certainty. Because test-retest
An accurate assessment of the visual field is essential for the variability is high in glaucomatous fields, confirmatory tests are
diagnosis and monitoring of glaucoma. Difficulty in obtaining often required to verify true progression.
quantifiable results with kinetic perimetry has led to automated Early glaucomatous defects tend to occur as scotomata in the
static perimetry of the central 24-30° becoming the norm for arcuate areas (10- 15° from fixation), particularly superiorly. A
glaucoma work as it is uncommon for glaucomatous field defects nasal step may occur. With time the defects coalesce, central
to occur elsewhere in the visual field in the absence of a defect in fixation being spared until late in the disease. Because standard
this area . Computerized field tests require cooperation and perimetry is not sensitive to very early glaucomatous defects new
concentration from the patient so faster test strategies are of psychophysical tests have been developed that may be more
particular benefit. Each test is a subjective assessment of visual sensitive to the purported selectivity of ganglion cell damage,
function and the results depend on the patient's attention, although none has yet entered routine clinical practice.
mental ability and general health as well as physiological
parameters such as pupil diameter and lens opacity. A pupil
diameter of less than 2 mm may produce a generalized reduction
SINGLE FIELD ANALYSIS Eye: LEFT
in sensitivity, as can lens opacity. Encouragement and practice Centtal24- 2 10:
can improve the reliability of results. Recently a new test Slimulus: Ill, WHITE Background: 31.5 as-b Test Date: 22 Jun 2000 ... 54
algorithm for the Humphrey perimeter, the Swedish Interactive B.li.nd Spot Check Size: Fixation Target: CENTRAL Test Time; 11:47:15 AM
R.XUsed: OODS DC x • Pupil Diameter: 5.0 mm VA: 20/20
Thresholding Algorithm (SITA), has been introduced that Strategy: FUU..

shortens the test time without compromising test quality.

Fixation Losses: 0122
Visual field testing techniques in chronic glaucoma may be f alse Pos Errors: 0120
24 24 25 26
25 20 17 27 24 22
divided into those for diagnosis and screening and those for False NegElrors: 2/12
Test Duration: 14:06 26 28 22 22 27 26 19 18
monitoring. The former requires a level of accuracy sufficient for f ovea: 36 dB 27 <0 22 26 2 17 23 22 21
30"
identifying disease, whereas the latter requires the most sensitive 26 2 ~ JJ JJ B u u n
and reliable method available that is compatible with the 26 29 26 28 31 30 28 26
v 29 29 28 TJ '!]
patient's skill and concentration taking into account the duration
28 24 23 22
of the test, cost and availability of ancillary staff. True
progression of disease must be distinguished statistically from -2 -2 -1 0
-6 -1 -7 -1 -1 -3 -5
normal fluctuations in the visual field with time. A sequence of ·2 -8 -1 1 -2 -4
-2 -1 -7 -8 -4 -5 -10 -10 -1 0 -6 -1 -2 -3 -9 -8
-2 -9 -6 -31 -14 -7 -6 -5 -I -1 -5 -30 -13 -6 -5 -4
-2 I I -3 -3 -1 -5 ·2 -1 2 2 -2 -2 0 -3 GlaucomaHernifit:ldTest:
-3 -1 -5-3 0 -1 -2 -2 -2 0 ·4 -2 I 0 -1 -1 IWNLI BljONL l
·;;+-'"' -3 -1 -1 -2 -3 -2 -2 0 0 -1 -2 -1
OutsideNorma!Lirruts
·;:; -1 -5-6 -6 0 -4 -5 -5
'Vi
c MD· -461 dB P<l'Y•
Q) Patum
V\
T01al
PSD: 62ldB P<OS'Y.
Deviation Deviation
Iii Sf: 2.03 dB
c
·;:; CPSD: S 83 dB P < 0.5%
~

. ..
..... m . .. ;;::
0
V\
00 • ;;:; .. :.;; ' Ill ••

0 ~- ~ .. !li • • • ~

=~
Q)
> Probability Symbols
0 : : P<5%
Nasal Fovea Temporal ~ P <l%
tQ P < 1%
• P < O.S%
Humphrey lnsttwnents
ADivisionofCar!Zelss,lnc.
SFW version AS. !
CopyrightC 1994-99

Fig. 7.24 A single test result from the Humphrey computer

assisted perimeter showing an upper arcuate defect in the left eye
on the 24-2 grid with its 'stat pac' analysis. The print out gives
V\

0 details of age and optical correction used and indicates patient

11)
reliability (fixation losses, false-positive and false-negative
u
0
u,_
responses). Absolute values of retinal sensitivity at each point
(upper numerical grid in decibels) are compared wit11 age-matched
Nasal Fovea Temporal normal values ('total deviation') for each point in the grid. Pattern
deviation is a measure of focal loss corrected for generalised loss of
Fig. 7.23 Computerized perimetry measures the retinal sensitivity and is therefore a more specific indicator of
sensitivity at selected points within the island of vision. Common glaucomatous damage. These are expressed both numerically and
statistical indices calculated are for overall loss of retinal sensitivity as probability maps, with the 'global indices' MD and PSD
(mean deviation; MD) and focal loss of sensitivity (pattern reflecting total and pattern deviation respectively. The 'Glaucoma
standard deviation; PSD) relative to age-matched normal values. Hemifield Test' is an analysis of the symmetry between upper and
The indices simplify the sequential interpretation of visual field lower hemifields, reported as within normal limits, borderline or
changes. outside normal limits (see Ch. 1) .
PRIIVIARY GLAUCOMA

Sep 1994

. :,. .

Mar 2000 Apr 2001

.. .. ...
.... ........
. ....
.
,, , '

Fig. 7. 25 A sequence of Humphrey grey-scale printouts from a 65-year-old woman with glaucoma in the right eye followed from
September 1994 to April 2001. Fluctuation makes it difficult to determine whether the field is stable or progressing without statistical
analysis.

Fig. 7.26 The change in retinal sensitivity at each point over

time can be compared using linear regression analysis for each of
the 76 test locations in the 24-2 test using software known as
'Progressor'. The series of bars denotes each test in sequence from
left to right. The longer the bar, the greater the sensitivity loss, with
the probability that change is significant indicated by colour; red
and white bars denote the highest probability. In the same patient
as Fig. 7 .28, several locations in the arcuate and nasal regions show
significant change.
 PRIMARY OPEN ANGLE GLAUCOMA ~

TREATMENT

Fig. 7.27 The goal of glaucoma management is to slow the

~
I progression of the disease in order to prevent visual loss that
Higher
Short
I impairs the patient's quality of life. At present the only modifiable
target
lOP I High I factor proven to slow disease progression is lOP reduction and this
~ Early
I i can be targetted at a level ranging from the low teens to the mid
twenties. Deciding on a 'target lOP' involves estimating such

$
Initial pressure
I expectancy
Life I at which damage factors as the rate of disease progression, life expectancy and the
occurred risk of vision loss in each patient and needs to be updated in the
Lower ~ Advanced
I ~ light of clinical findings. Some patients with ocular hypertension
target
lOP
? I
I
Low
I
are given 'prophylactic' treatment if the lOP is considered
sufficiently high that there is a risk of glaucomatous damage or
~ Long
I I central retinal vein occlusion.
By courtesy of the European Glaucoma Society.

Laser trabeculoplasty

Precisely focused argon laser burns on the trabecular meshwork
produce a significant reduction in outflow resistance and a fall in
lOP of 6-9 mm Hg in some patients. This treatment forms a
useful adjunct to medical treatment. It is most successful in the
elderly patient with POAG who has a pigmented trabecular
meshwork and for whom only a moderate pressure reduction is
required. Unfortunately, even in these favourable cases the
beneficial effects may lessen with time with only 50 per cent of
patients in the successfully treated group maintaining this
response for 5 years.

INCORRECT CORRECT

Fig. 7.28 This diagram of the angle and trabecular meshwork

shows the varying responses seen following laser treatment. These
range from (on the left) malpositioned treatment, excess treatment
(large bubble formation and later synechia! adhesion of the iris) to
insufficient treatment. The right side shows the appearances seen
with adequate treatment (blanching of the meshwork).

Medical therapy

In the developed world medical therapy is usually the first line of when used in combination treatment, mechanism of action.
treatment provided the patient is able to comply. Choice of drug When combination therapy is needed patients are most likely to
is governed by the drop potency, ease of use (delivery and comply with the simplest regimen. Table 7.5 outlines the various
frequency), side-effect profile (topical and systemic), cost and regimens that may be used together with their adverse effects.
PRIMARY GLAUCOMA

Table 7.5 Medical treatment of glaucoma

Class of drug Generic Frequency Aqueous Trabecular Uveoscleral Ocular Systemic
name of use production outflow outflow side-effects side-effects
(per day)
Adrenergic agents Timolol Once (morni ng) H Dry eye, Bronchospasm,
(~blocker) or twice sting ing on bradycardia, systemic
insti llation hypotension, exercise
intolerance, impotence,
Levobunolol H depression
Masking hypoglycaemia
Carteolol H (in diabetics)
Betaxolol t

Adrenergic agents Brimonidine Two or th ree H (i) Allergy Dry mouth, lassitude,
(a agonist) times nightmares;
respiratory depression
(in children)
Apraclonidine H Tachyphylaxis, Dry mouth
(al lergy)

Prostaglandin analogues Latanoprost Once (evening) it Mild hyperaemia, (Bronchospasm-rare)

increased iris
pigmentation
(green/hazel
eyes), eyelash
growth, (cystoid
macula oedema
in aphakia-
rare, reversible)

Travoprost it Transient
hyperaemia,
(increased iris
pigmentation),
eyelash growth

Prostamide analogues Bimatoprost (i) i ii Transient hyper-

aemia, (increased
iris pigmentation),
eyelash growth

Carbonic anhydrase Dorzolamide Th ree times Burning, itching, Bitter taste

inhibitor (topical) reduced corneal
endothelia l cell
function

Brinzolamide Burning, itching,

reduced corneal
endothelial cell
function

Carbonic anhydrase Acetazolamide One to four times Ht Paraesthesia, fatigue,

inhibitor (systemic) depression, electrolyte
imba lance, renal ca lculi;
Stevens- Johnson
syndrome, blood
dyscrasia (rare)

Cholinergic agents Pilocarpine Four times (t) it (t) Miosis, Only in overdose
(agonist) accommodati ve (nausea, vomiting,
spasm, posterior cardiac)
synechiae

Dehydrating agents Mannitol Intravenous HH Electrolyte disturbance,

urinary retention

Laser cyclophotocoagulation
Transscleral diode laser cyclophotocoagulation has largely
replaced other forms of ciliary body destructive procedures for
lowering lOP such as Nd:YAG laser or cryogenic
cyclodestruction. Cyclodestruction is usually reserved for eyes
with end-stage glaucoma and a poor visual prognosis or blind
Fig. 7.29 The ciliary body position is identified by transillumination through the pupil and transscleral diode laser is applied in a
circumferential sequence.
By courtesy of Mr K Barton.
Surgery
Fistulizing surgery such as trabeculectomy without adjunctive
antiscarring therapy will lower lOP to the mid teens for at least
five years in 75 per cent of patients with POAG aged over 50
years. This success rate falls considerably in certain groups: those
susceptible to scarring (young, black or atopic patients, those
with previous conjunctival surgery, using chronic glaucoma
medication or blepharitis), and those with a damaged
blood-aqueous barrier (aphakia, uveitis, rubeosis, concurrent or
subsequent cataract surgery). The most favourable results are
seen in patients who have surgery early in the course of the
disease. Eyes at high risk of surgical failure or requiring a
postoperative lOP in the low teens may be helped by
peroperative antifibrotic agents such as ~ irradiation,
PRIMARY OPEN ANGLE GLAUCOMA 20
eyes that are symptomatic from increased lOP. It also has a role
in refractory glaucoma in which surgical procedures are high risk
or likely to fail such as neovascular and aphakic glaucoma, and
conjunctival cicatricial disease or those that have already failed
surgical treatment.
5-fluorouracil (5-FU) or mitomycin C. Nonpenetrating surgery
('deep sclerectomy' and 'viscocanalostomy') has been advocated
to avoid the complications of trabeculectomy, such as early
hypotony and subsequent cataract. The surgery is
'nonpenetrating' because a trabecular/corneal membrane is
preserved after the inner wall of Schlemm's canal and external
part of the trabecular meshwork have been peeled, through
which aqueous percolates. The way in which this surgery works
is controversial; filtering blebs are frequent, both uveoscleral and
transscleral filtration may be increased, and microperforations in
the trabecular meshwork may create a gentle trabeculectomy.
lOP reduction is less in comparison to trabeculectomy.
zone of increased
.----__:.,:.::..;:.;.;;4'-1 vascularity around
drainage bleb
Fig. 7.30 Following a trabeculectomy this patient developed a
limbal filtration bleb at the 12 o'clock position. Notice the
relatively avascular central area and surrounding blood vessels,
indicating a successfully established bleb. Vascularization of the
whole bleb is usually a sign of failure with loss of control of lOP.
06 PRIMARY GlAUCOMA

microcysts in
conJunctiva

Fig. 7.31 Microcyst formation in the conjunctiva over the bleb

(to the right of the beam) is a good indication that it is
functioning.

avascu lar bleb

Fig. 7.32 Antiscarring treatment, particularly with mitomycin C,

can produce a very thin translucent and avascular bleb. Such eyes
have a substantial risk of postoperative hypotony or late bleb
infection.

Fig. 7.33 A thin-walled bleb that has become infected and filled with pus causing endophthalmitis. Endophthalmitis is more frequent in
diabetics, after the use of adjunctive anti proliferative agents, in thin-walled or leaking blebs and with blebs in the interpalpebral fissure .
Trabeculectomies should be performed between the 11 and 1 o'clock positions and never inferiorly.
By courtesy of Mr TWells.

PRIMARY ANGLE CLOSURE
Primary angle closure (PAC) occurs when aqueous drainage is
prevented by contact between the peripheral iris and the
trabecular meshwork in the absence of other pathological
processes such as iris neovascularization. In most cases the
condition probably begins with intermittent and reversible
appositional contact, which, if prolonged or associated with
ocular inflammation, becomes synechia! and irreversible from
scar formation. In some cases prolonged apposition may
irreversibly impair trabecular function so that even reopening the
angle with pilocarpine, laser iridotomy or surgery does not
restore outflow. Long-term topical pilocarpine therapy probably
enhances the risk of synechia! angle closure.
PAC is a major cause of glaucoma blindness worldwide. It is
common among people of East Asian origin: the Inuit in Arctic
regions of Alaska, Canada and Greenland are most severely
affected and the Chinese are at higher risk than native South-
East Asian races (Indonesian, Malay, Thai and Vietnamese). The
risk of angle closure in India is lower than in China but higher
than in Europeans. The relative risk of angle closure in women is
two to three times higher than in men and risk increases after 30
years of age. An estimated 1. 7 million people in China are blind
Table 7.6 Current classification of primary angle closure
Type Description
PAC suspect Narrow drainage angle considered to be at risk of closure
PAC Significant angle closure and ra ised lOP due to iridotrabecula r con tact or PAS not attributable to other pathology. Optic
nerve considered to be unaffect ed by glaucoma
PACG Drainage angle closed or capable of closure accompanied by signs of glaucomatous optic neuropathy
PRIMARY ANGLE CLOSURE
Fig. 7.34 Tube and plate surgery increases the area for aqueous
absorption and bypasses increased resistance from postoperative
subconjunctival fibrosis. A silicone tube connected to a drainage
plate or sump device is introduced into the anterior chamber; the
massive increase in area for aqueous drainage provided by the
sump allows for lOP control in a number of problem glaucomas.
Several drainage implant designs have been marketed, although the
principle is the same in all.
from glaucoma; more than 90 per cent of these cases are
attributed to PAC.
Recent research has highlighted significant differences in the
clinical course of PAC between European and Asian people
leading to a radical rethink in the way the disease is classified. In
the Western world PAC has usually been recognized when the
condition is acute and symptomatic, so that it has traditionally
been classified by the presence or absence of symptoms: acute
with unremittingly florid pain and decreased vision; intermittent
with self-limiting symptoms; and chronic when asymptomatic
but usually with associated past symptomatic attacks of raised
lOP. However, this approach is flawed. In Asia, between 50 and
75 per cent of people with glaucomatous optic neuropathy from
angle closure do not suffer the classical symptoms familiar to
Western ophthalmologists. Furthermore classification by
symptoms does not reflect the severity of damage to ocular
tissues or visual loss and this classification does not help to guide
management in individual patients. It is now widely
acknowledged that the term glaucoma should be used only when
glaucomatous optic neuropathy is present. The term primary
angle closure (PAC) is recommended for significant angle closure
but with a normal optic nerve (Table 7.6).
S PRIMARY GLAUCOMA

synech iaI
closure

pigmented
midtrabecular
meshwork

Fig. 7.35 (Left) This goniophotograph shows an area of transition from an open angle with a moderately pigmented mid trabecular
meshwork to an area of broad synechia! closure; the synechia! adhesion has occurred at the level of the anterior trabecular meshwork.
(Right) The morphology of peripheral anterior synechiae (PAS) may vary in height and width. This figure shows areas of broad, low PAS
and of high, narrow PAS. Within the area of narrow PAS, iris stromal tissue can be seen stretched out under tension, which may break
during dynamic gonioscopy to leave a pigment blot on the trabecular meshwork.

pigm ent o n
meshwork

Fig. 7.36 Following treatment of angle closure the angle may be irreversibly damaged, even in the absence of PAS, from damage to the
trabeculocytes covering the trabecular plates. This view of an angle shows diffuse pigment deposition across the trabecular meshwork after
the angle was opened by laser peripheral iridotomy. This appearance has been likened to footprints in the sand and a high-water mark.
Despite the angle being open trabecular damage was sufficient to cause persistently increased lOP.
 PRIMARY ANGLE CLOSURE GLAUCOMA 20

peripheral anterior
synechia (PAS)

trabecular meshw ork

Fig. 7.37 A histological section demonstrating adhesion between

the peripheral iris and the trabecular meshwork extending past
Schwalbe's line on to the corneal endothelium. This constitutes a
very high PAS.

Fig. 7.38 The van Herick test has been

suggested for rapid assessment of limbal
anterior chamber depth (LCD) and therefore
risk of angle closure. A fine, bright slit-lamp
beam is shone on to the temporal limbus so
that it falls perpendicular to the surface of the
eye. The anterior chamber is then viewed at
an angle of 60° nasal to the illuminating
beam. Depth at the periphery is estimated
peripheral iris 1------+1 and expressed as a fraction of peripheral
corneal thickness. LCD of one-quarter or less
of corneal thickness constitutes a significant
risk of closure. This technique is not,
however, a substitute for gonioscopic
examination.

PRIMARY ANGLE CLOSURE GLAUCOMA

Symptomatic PAC is difficult to ignore: there is dramatically
reduced visual acuity, ciliary injection and pain sufficiently
intense to cause nausea and vomiting. Intermittent episodes of
PAC typically occur when an individual is at home engaged in
sedentary past times such as reading or sewing. Symptoms are
often precipitated by dim light, such as in the cinema. Impaired
vision is described as milky and hazy, and like 'looking through
smoke'; multicoloured haloes are sometimes seen. However, the
condition may be completely asymptomatic. Even with advanced
angle closure and lOP exceeding 70 mmHg, the cornea may
remain clear, and the eye white and quiet. Patients without
symptoms are most at risk of severe visual loss, as they often
present only when one eye is blind and the other severely
glaucomatous. In patients with dark brown irides, the anterior
chamber may not appear especially shallow, even if there is
significant angle closure and careful gonioscopy is needed to
confirm the diagnosis.

Trabecular
Iris stromal Corneal
damage and
atrophy, schisis and endothelial
peripheral anterior
muscle damage cell loss
synechiae
i
Pr imary
angle
closure

Glaukomflecken
1
Glaucomatous lschaemic optic
or lens nuclear
optic neuropathy neuropathy
sclerosis Fig. 7.39 Sequelae of primary angle closure.
PRIMARY GLAUCOMA

co ngested
co njunctiva
semi dilated
irregular pupil

Fig. 7.40 During an attack of angle-closure glaucoma the rise in

lOP is associated with infarction of the iris tissue and an associated
inflammatory response. There is circumlimbal injection and
corneal oedema which can be seen by the irregular light reflex on
the corneal surface.

Fig. 7.41 After an episode of symptomatic angle closure the iris may have suffered a sectorial infarction of the sphincter muscle causing
distortion and recognized clinically by its whorled appearance. If this is severe the eye is left with a poorly reactive ovoid pupil.

depigmentat ion
<tt"""c.,.,.,-"-"'~-'id-,.,_--l secondary to iris
at rop hy
spiral ling

Fig. 7.42 Iris stromal atrophy may also occur after an episode of
symptomatic angle closure. The distortion of the pupil contour
suggests damage to the iris musculature.
 PRIMARY ANGLE CLOSURE GLAUCOMA 211

Fig. 7.43 Lens damage following angle closure with elevated rise
in lOP is seen as a white granular anterior subcapsular opacity
with an irregular edge; this is called glaukomflecken. Over time
these opacities come to lie deeper in the lens as new cortical lens
fibres are laid down (see Ch. 11).

subcapsular
epithelial 1---.,J.'----*"
cel l nucleus

Fig. 7.44 Histological section of a lens with glaukomflecken

showing foci of lens epithelial cell necrosis.

optic atrophy

Fig. 7.45 Photographs of the optic discs of a patient 6 months

after an episode of symptomatic angle closure in the right eye .
Although lOP remained well controlled after the attack, the right
optic nerve is flat, pale and atrophic from vascular and neuronal
damage; by comparison the left optic nerve is healthy and normal.
Should the lOP remain raised after the attack the disc would
become cupped and indistinguishable from that seen with POAG.
Z12 PRIMARY GLAUCOMA
MECHANISM OF PRIMARY ANGLE CLOSURE
Identifying the mechanism responsible for angle closure is
essential for effective treatment. Pupil block is responsible for
80-90 per cent of all cases. Closure may occur first at the deepest
part of the angle recess (closure at the bottom of the angle) or
between the midperipheral iris and Schwalbe's line (closure at
Schwalbe's line). Differing patterns of pigment distribution on
the trabecular meshwork may be seen with these two types of
angle closure although their clinical course and prognosis
appears similar. The lens may be involved either as a primary
phenomenon, in which the lens is thicker and more anteriorly
positioned than normal, or as a secondary phenomenon in which
a hypermature lens swells and further shallows an already narrow
chamber angle .
Non-pupil-block angle closure is an umbrella term
encompassing plateau iris and peripheral iris crowding. Plateau
a b
Shal low
anterior
chambe r
with pupil
block
iris convexity
Closed angle Open angle
anterior
chamber
Fig. 7.47 Ultrasonographic biomicroscopy of the peripheral anterior chamber. On the left, the profile of the iris is anteriorly convex and
characteristic of pupil block, causing closure of the angle. On the right, after laser iridotomy, the iris profile has changed to become much •
flatter with a residual plateau configuration.
By courtesy Mr G Gazzard and Dr P Chew.
iris configuration describes the appearance of a peripheral iris
that rises from its insertion and then makes an abrupt angulation
away from the corneoscleral coat at its insertion and is seen to
some degree in 5-8 per cent of adults. The appearance of plateau
irides varies greatly, both in the level of the plateau relative to the
trabecular meshwork and in the width of the gap between iris and
trabecular meshwork; these influence the risk of closure. The
plateau iris syndrome describes an eye with plateau iris
configuration and a patent iridotomy or iridectomy that
subsequently suffers further angle closure. Peripheral iris
crowding describes angle closure without pupil block and is seen
on gonioscopy as a very bulky peripheral iris thrown into
circumferential folds in a shallow peripheral anterior chamber to
occlude the angle.
c
Fig. 7.46 The anterior chamber profile with a
normal angle, angle closure and following
peripheral iridectomy. Notice that in angle
closure the anterior chamber is shallower and
there is increased contact between the iris and
the lens, which causes a pressure gradient across
the pupil so that the peripheral iris billows
forwards to occlude the meshwork. Following
iridotomy the anterior chamber depth remains
unchanged but the iris falls back to open the
angle.
 Fig. 7.48 This line drawing illustrates the concept of relative
height of plateau iris in the development of significant angle
closure. (Left) With a low plateau apposition of the peripheral iris
to the meshwork will obstruct only the most inferior part of the
meshwork. (Right) With a high plateau apposition will cause
complete obstruction.

cornea

anterior chamber : .-/-·. ;~_..,...._------! w ide gutter

angulati on in
periphe ra l iri s
lens surface

closure at Schwalbe' s line

aqueou s f illed space

'---'-'"'T---...,---,.1 between peripheral iris
and trabecular meshwork

Fig. 7.49 This ultrasonographic biomicrograph shows plateau irides where the peripheral iris angulates abruptly prior to insertion in the
ciliary body. (Top) The gap between the iris periphery and trabecular meshwork on the left is wide (a wide gutter); (middle) there is a
narrow gutter; and (bottom) angle closure at Schwalbe's line . If closure occurs at the level of Schwalbe's line, pigment deposition may be
seen after treatment on gonioscopy as a wavy high-water mark. Alternatively, initial angle closure may be deep in the angle recess with
synechiae gradually creeping forward. 'Wide gutters' are a fairly common finding in East Asian people.
By courtesy of Mr G Gazz ard and Dr P Chew.

MANAGEMENT
The first priority in managing PAC, with or without optic nerve
damage, is to control lOP. This is most quickly achieved by either
medical or laser treatment. All classes of medical agents have a
role, particularly in treating symptomatic episodes, although
pilocarpine is unique in its ability to open some closed angles
mechanically. Definitive treatment is surgical with either laser or
conventional surgical techniques. Pure pupil-block angle closure
is managed successfully by laser iridotomy or surgical iridectomy.
Synechia! closure of more than 180° or glaucomatous optic
neuropathy usually requires a trabeculectomy. Lens related cases
of PAC are treated by lens extraction. Ciliolenticular block
'chink ' of angle YAG laser r---~(1
ot herwise iridotomy
optically closed
Fig. 7.51 Gonioscopic appearances before and after laser iridotomy show the angle has deepened and the meshwork can be seen.
disintegrat ing
l -1:.------:JI stromal su rface
Fig. 7.50 Iridoschisis is a rare condition seen in elderly patients
of unknown aetiology that can sometimes be associated with angle
closure. It is bilateral and usually starts in the inferior iris as a
fluffy separation of the anterior stroma.
('malignant glaucoma') following trabeculectomy is a risk in eyes
with very shallow anterior chambers for which combined lens
extraction and trabeculectomy may be safer (see Ch. 8).
Management of eyes with the plateau iris syndrome
(significant angle closure with a patent peripheral iridotomy) is
contentious. Topical pilocarpine, laser iridoplasty and lens
extraction may all be used, although the younger age of these
patients means that lens extraction and long-term pilocarpine
therapy may be inappropriate. Laser iridoplasty is potentially
useful for managing both pupil block and plateau iris PAC,
although its efficacy and safety remains to be proved.
open angle
(post-i ridectomy)

CONGENITAL AND DEVELOPMENTAL GLAUCOMA
The alternative term for congenital glaucoma, buphthalmos, is
derived from the Greek for 'ox eye' which refers to the acquired
megalocornea that develops in the child with congenital
glaucoma. Raised lOP in the first 18 months of life occurs at a
time when the corneal collagen (and scleral collagen) is still
plastic or 'stretchable'. In the UK congenital glaucomas are very
rare, but in countries where interrelated marriages are common
inheritance of recessive genes considerably increases the number
of cases.
Clinically congenital glaucoma presents as a group of rare
heterogeneous conditions which await further developments in
the understanding of genetics and development of the anterior
chamber angle for true classification. The trabecular meshwork is
derived from neural crest cells, and the congenital glaucomas
presumably arise from dysgenesis of these cells in utero. Primary
congenital glaucoma develops as a result of maldevelopment of
the outflow system of the eye although the angle appears normal
on gonioscopy and there are no other ocular abnormalities. It
occurs as an isolated ocular defect and there is often a degree of
asymmetry in the involvement of the two eyes. Idiopathic
buphthalmos is more common in male infants. Secondary
congenital glaucoma is associated with a wide range of other
ocular and systemic abnormalities such as anterior segment
dysgenesis and chromosomal abnormalities. Commonly
associated systemic syndromes are neurofibromatosis or the
Sturge-Weber syndrome, both of which involve neural crest cells.
Rarely buphthalmos may occur as a result of peripheral anterior
synechiae formation in the first 18 months of life, for example
from perforating corneal ulcers.
An alternative classification is descriptive, according to the
extent of the abnormality seen. There are three broad groups:
• Trabeculodysgenesis (primary congenital glaucoma, simple
buphthalmos)
• Iridotrabecular dysgenesis (e.g. Axenfeld-Reiger anomaly,
Rieger syndrome, aniridia)
• Iridocorneotrabeculodysgenesis (e.g. Peter's anomaly).
These anomalies do not inevitably produce glaucoma (the risk of
glaucoma with the Axenfeld-Reiger anomaly is 50 per cent).
CONGENITAL AND DEVELOPMENTAL GLAUCOMA 21.
SYMPTOMS AND SIGNS
It is a recurring tragedy that glaucoma in the neonate is easily
overlooked and the diagnosis delayed. In the established
condition there is megalocornea associated with intense
photophobia and lacrimation with a relatively white eye.
If the diagnosis is suspected examination under anaesthesia
should be carried out and the lOP measured as part of a
complete ocular assessment under an anaesthetic such as
ketamine which does not lower lOP. On examination the cornea
is enlarged from the normal 10- 11 mm up to 14- 15 mm in
diameter. Splits in Des~emet's membrane may be present. If the
corneal epithelium is opaque it must be removed by debridement
to examine the anterior chamber, the angle and iris structure and
the optic disc. Other important aspects of the continued
monitoring of the child include axial length, refractive error and
visual acuity measurement and treatment of amblyopia, as well as
the assessment of optic disc status (cupping can regress with
lowering ofiOP in children). Late complications in buphthalmic
eyes include corneal endothelial decompensation, giant retinal
tears and a recurrence of glaucoma in early adult life in eyes
previously considered cured.
TREATMENT
Treatment of congenital glaucoma is primarily surgical.
Goniotomy is the treatment of choice, although it is impossible
when the cornea has stromal haze. It works less well if the
horizontal corneal diameter exceeds 14 mm or if the child is
more than 3 years of age. Trabeculotomy is an alternative to
goniotomy, although the procedure violates the conjunctiva and
may prejudice future trabeculectomy surgery. It is suitable for
eyes with anterior segment dysgeneses or when the drainage
angle cannot be visualized. Trabeculectomy is indicated in eyes
with failed angle procedures and when a low target lOP needs to
be achieved. An antifibrotic agent, such as ~ irradiation or
mitomycin C, is usually required to combat the aggressive
healing response in children. For severely affected eyes,
cyclodestructive procedures or insertion of a silicone tube can be
considered. Buphthalmic eyes can have significant refractive
error, and accurate refraction and treatment of amblyopia play an
important part in the successful visual outcome.
Fig. 7.52 This 10-month-old boy has corneal enlargement and
oedema typical of buphthalmos. Lacrimation and intense
photophobia are the usual presenting symptoms. The child will
often bury its head in a pillow to avoid the light from a window.
6 PRIMARY GlAUCOMA

Fig. 7.53 A high-power view of the cornea demonstrates the appearance of 'splits' in Des<;emet's membrane which are probably caused
by tearing of the membrane associated with the enlargement of the cornea. Horizontal splits called Haab striae are characteristic of
buphthalmos. These usually develop in the first 18 months after birth and are a sign of uncontrolled lOP. They are sometimes associated
with transient stromal oedema, which invariably subsides with the reconstitution of Des<;emet's membrane. Similar 'splits' can be seen as a
result of birth trauma to the normal eye with a normal cornea (in which case they are often horizontal) or with posterior polymorphous
dystrophy (see Ch. 6).
By courtesy of Professor Peng Khaw.

anteriorly inserted iris

major arterial circle

Fig. 7.54 Examination of the angle may reveal maldevelopment

of the iris, abnormal adhesions between the peripheral iris and the
trabecular meshwork associated with maldevelopment of the angle,
and in some instances anomalies of the cornea and lens. This
histological appearance of the angle demonstrates the abnormal
anterior insertion of the iris together with poorly formed trabecular
structures.

IRIDOTRABECULAR AND IRIDOCORNEOTRABECULODYSGENESIS

(~osterior embryotox~ is the term given to an unusual
prominence of Schwalbe's. line that rotates outwards to be seen
as a white band inside the limbus. It occurs in about 1.5 per cent
of normal people and is considered to be hyperplasia of tissue on
f!le posterior cornea near the angle; it is of no pathological
~ignificance.
Iris strands to a prominent Schwalbe's line are known as
Axenfeld's anomaly; if glaucoma is present, the condition is
known as Axenfeld's syndrome. Rieger reported similar cases but
with additional ocular abnormalities such as microcornea,
corectopia (eccentric pupils) and polycoria (multiple pupils) .
Extended pedigrees show considerable variation in affected
family members and for this reason many authors group them
together as the Axenfeld- Rieger malformation although the
conditions are both genetically and phenotypically
heterogeneous. Defects in FOXCJ and PITX2 may give rise to
this spectrum of abnormality. The extent of abnormality may
vary between individuals with the same gene mutation and
different mutations can cause the same clinical appearance.
These ocular features together with systemic abnormalities, such
as abnormalities of the teeth and facial bones (hypertelorism),
are referred to as Rieger's syndrome. Peter's anomaly (see Ch. 6)
consists of adhesions from the iris collarette (and sometimes
lens) to the posterior corneal surface which has a central opacity
and stromal defect. It is usually bilateral (80% per cent) and
other defects of anterior segment development may be present.
Glaucoma occurs in a substantial number (50- 70 per cent) of
cases. The central corneal opacity often clears substantially with
control of the lOP.
Fig. 7.55 The anterior chamber angle in a patient with
Axenfeld's anomaly shows characteristic multiple abnormal iris
processes extending anteriorly to be inserted into Schwalbe's line.

iris strand to col larette

Fig. 7.56 Peter's anomaly is a developmental anomaly of the

anterior chamber in which adhesions exist between the iris and the
cornea. It is u sually associated with localized lens and corneal
opacification. This example shows a very mild example with a
localized corneal opacity connected by an iris strand to the
collarette.

ANIRIDIA
Aniridia is a bilateral developmental anomaly in which the iris
stub extends forwards from the iris root as a small cuff which
may form peripheral anterior synechiae and occlude the angle.
Glaucoma occurs in about 30 per cent of patients, usually in the
second decade of life . Corneal opacity and peripheral
vascularization is common and is thought to be due to an
abnormality of limbal stem cells. Lens opacities are common
findings, too, and most patients have nystagmus and macular
hypoplasia. Cases may · occur sporadically or be inherited as an
horizonal
:4"'8,_~~---1 displacement of
iris towa rds limbus
lens opacity
'featureless'
anterior
iris surface r--T<<t"'+~ZHI,~
Fig. 7.57 Rieger's anomaly is associated with iris hypoplasia,
posterior embryotoxon and angle anomalies. Glaucoma may
present in infancy but is more usual in the first to third decades of
life. Notice the grossly abnormal iris with hypoplasia of the
anterior iris surface and distortion of the pupil (iris pigment
epithelium may be seen at the temporal margin) .
Fig. 7.58 Associated defects (Reiger's syndrome) include
maxillary hypoplasia and dental deformities.
autosomal dominant trait associated with abnormalities of the
PAX6 homeobox gene. Sporadic cases show a high incidence of
nephroblastoma and all affected infants should be screened for
this with renal ultrasonography. Surgical treatment is difficult
because the lack of an iris diaphragm is associated with forward
movement of the lens in the postoperative period and a risk of
malignant glaucoma. Many of these operated eyes develop lens
opacities that require removal at an early age.
 CONGENITAL AND DEVELOPMENTAL GLAUCOMA u

Fig. 7.59 This eye of a 2-year-old girl seen at EUA shows a

normal-sized cornea. There is aniridia exposing the equator of the
lens and zonular fibres. lOP was normal at this stage.

peripheral
anterior f---+-'f
synechiae

Fig. 7.60 Goniophotograph of an eye with aniridia demonstrates

the formation of peripheral anterior synechiae which led to the
development of intractable glaucoma in early adult life .
Secondary Glaucoma
I<.eith Barton

Classification of Secondary Glaucoma

Pretrabecular Outflow Obstruction
Trabecular Outflow Obstruction: Secondary Open Angle Glaucoma
Post-trabecular Outflow Obstruction: Raised Episcleral Venous Pressure
 CLASSIFICATION OF SECONDARY GLAUCOMA

Secondary glaucomas occur when the intraocular pressure (lOP)
is raised as a result of another ocular condition or its treatment.
These conditions form a small proportion of all glaucoma but
they frequently produce the most difficult problems in diagnosis
and management. The diagnosis of secondary glaucoma is often
made before the development of glaucomatous cupping and field
loss as without treatment these will almost certainly develop with
time. Patients presenting with a high lOP secondary to, for
example, a traumatic hyphaema are considered to have
secondary glaucoma (although strictly speaking they will be
suffering from secondary ocular hypertension).
Increased lOP secondary to other conditions is almost always
due to a fall in outflow facility. Very rarely raised lOP can be seen
with haemodilution from haemodialysis or cardiopulmonary
bypass.

Table 8.1 causes of secondary glaucoma outflow obstruction

Pretrabecular Trabecular Post-trabecular
With pupil block Without pupil block Trabecular o bstruction/damage Raised episcleral venous pressure
Inflammation Posterior segment disease Pigmentary glaucoma Carotico-cavernous fistula
Lens/IOL related Malignant glaucoma Pseudoexfoliation of lens capsu le Sturge-Weber syndrome
Small eyes Lens induced
Cellular occlusion of ang le Silicone oil
Haemolytic
Siderosis
Tumours
Uveitis
Steroid induced

Treatment of the secondary glaucomas is directed first at the
cause of the condition: inflammation is suppressed, a swollen
lens is removed. This may not always control lOP successfully as
the trabecular meshwork may have been damaged extensively so
that even after removal of the cause long-term glaucoma therapy
is still required. Many secondary glaucomas present with an
extremely high lOP and require emergency treatment with
intravenous or oral carbonic anhydrase inhibitors or
hyperosmotic agents. The long-term strategy then depends on
the predicted natural history of the condition; the therapeutic
approach differs considerably with each individual type of
glaucoma. Topical beta-blockers, alpha-agonists and oral or
topical carbonic anhydrase inhibitors are very useful and
prostaglandin agonists may be effective, even in the presence of
angle closure . Pilocarpine may cause vasodilatation and
exacerbate blood- aqueous barrier breakdown and is best avoided
in patients with these conditions. Many secondary glaucomas
respond poorly to maximum tolerated medical treatment in the
long term and require trabeculectomy with antiproliferative
treatment, aqueous shunt devices or cyclophotocoagulation;
fortunately ocular involvement is often asymmetrical.

PRETRABECULAR OUTFLOW OBSTRUCTION

In this group of conditions iris or other tissue obstructs the angle
to prevent aqueous from reaching the trabecular meshwork. It is
important to ascertain whether pupil block is present as this will
affect treatment. On gonioscopy an angle that is closed by
apposition indicates pupil block and indentation gonioscopy will
help exclude synechia! closure. Posterior segment disease must
be excluded by fundus examination or, if the media is opaque, by
ultrasonography.
1 Posterior synechiae from inflammation in the anterior
segment
2 Occlusion of the pupil in pseudophakic and aphakic eyes by
the implant or vitreous gel
3 Forward lens movement or swelling of a cataractous lens.
Inflammation in the anterior segment

Inflammation of the anterior segment producing ring posterior

SECONDARY ANGLE CLOSURE WITH PUPIL BLOCK
Secondary pupil block occurs when the iris becomes adherent at
the pupillary margin to the lens and restricts aqueous flow
forwards. Iris bombe shallows the anterior chamber peripherally
although it remains relatively deep centrally. Raised lOP may
persist after an attack of pupil block from any cause if a large
proportion of the angle has been closed by peripheral anterior
synechiae (PAS) formed during the attack or if the trabecular
meshwork has become damaged.
Possible reasons for pupil block are:
synechiae to the lens implant or vitreous face, and occluding the
pupillary aperture is an important cause of secondary angle-
closure glaucoma with pupil block. Pupil block may develop
insidiously in low-grade iritis with gradual seclusion of the pupil
or suddenly in acute iritis. Treatment is aimed at preventing
seclusion of the pupil with topical steroids and mydriatics but for
the established condition laser or surgical iridectomy is necessary
to break the block. Before the advent of YAG laser iridotomy
peripheral iridectomy was performed routinely during most
intraocular surgical procedures to avoid potential pupil block
from postoperative inflammation.
 Fig. 8.1 In this patient with uveitis
posterior synechiae pupil block due to seclusion of the
pupil is evident from the forward
convexity of the iris resulting in a
shallow peripheral anterior chamber,
whereas the central chamber remains
deep. The deep central anterior
chamber distinguishes pupil block
from malignant glaucoma with
forward movement of the iris- lens
diaphragm secondary to posterior
segment pathology or pupil block
from intumescent cataract.

convex iris
iris no longer in
contact w ith
posterior synechiae
peripheral co rn ea

peripheral iris in
contact with corneal flattening of t he
endothelium iris profile

Fig. 8.2 These two slit-image photographs show the same patient (left) before and (right) after treatment. Pupil block and iris bombe are
present. A deepening of the peripheral part of the anterior chamber is clearly evident following laser iridotomy (right).

Pupil block in pseudophakic and aphakic eyes

Modern techniques of phacoemulsification cataract surgery with
posterior chamber lens implantation are sufficiently free from
postoperative inflammation not to require an iridotomy and
pupil block is rarely seen in these eyes. When pupil block does
occur it may be due to pupil capture of the implant or from
occlusion of the pupil by posterior synechiae to the implant or
lens capsule remnants. Intracapsular cataract surgery used to
cause pupil block as an acute event although sometimes this did
not become apparent until weeks later. Similar findings may be
seen with aphakia when posterior synechiae can form between
the iris and anterior hyaloid face . Pupil block is suggested by a
combination of raised lOP and peripheral shallowing of the
anterior chamber. Although extensive prolapse of gel through the
pupil sometimes occurs there is usually little vitreous prolapse
and the central anterior chamber is of normal depth with
peripheral shallowing.
The established condition is treated by laser iridotomy and,
when successful, there is immediate deepening of the peripheral
anterior chamber. Laser iridotomies, however, are small and may
become occluded with fibrin or vitreous gel. A surgical
iridectomy can therefore be required or, sometimes, a vitrectomy
is necessary performed to re-establish aqueous flow. Eyes
containing silicone oil should have a surgical iridectomy
performed inferiorly as the oil floats up to occlude a superior
iridotomy. Pseudophakic pupil block can occur in eyes with an
anterior chamber lens without iridectomy or if an iridotomy is
nonfunctioning from blockage by vitreous or capsular remnants.
A rigid anterior chamber lens may maintain axial anterior
chamber depth with iris ballooning around the edges of the lens
making the periphery of the anterior chamber more shallow and
occluding the angle.
 NDARY GLAUCOMA

iris pigment epithelium

adherent to the .anterior
hyaloid face, stretched by 1-f'--------T'-'-'"S~ aphakic eye
attempted pupillary
dillation

shallow anterior
chamber~~~'----~
and iris bombe

Fig. 8.3 In this patient there is pupil block from posterior synechiae to the
vitreous face in an aphakic eye. The slit-lamp image shows peripheral shallowing
of the anterior chamber. The extent to which the gel prolapses into the anterior
chamber determines the central depth.

Fig. 8.4 Anterior chamber intraocular lens implantation without peripheral iridectomy is likely to cause pupil block. In this case the iris
can be seen bulging forwards around the implant. Although the angle can often be reopened by a laser iridotomy this readily reoccludes
with vitreous and so does not reliably prevent recurrence . Surgical iridectomy is definitive but difficult to achieve through a corneal
phacoemulsification wound unless it is placed temporally. Temporal iridectomies may cause glare or monocular diplopia, however, and so
surgical entry by a separate superior corneal incision is preferable.
 Fig. 8.5 Silicone oil floats on aqueous humour. Eyes with
posterior segment silicone oil retinal tamponade require an inferior
iridectomy to prevent pupil block.

rward movement of the anterior lens surface

of the lens, anterior dislocation or age-related eyes require lens removal or iridotomy. Angle closure may still
changes in the lens can all produce pupil block and angle occur after iridotomy as a result of progressive increase in antero-
by forward movement of the anterior lens surface. These posterior depth of the lens.

f ixed
s:-;+------'"f'-"~~~~~ semidi lated
pup il

cat aractous
lens

opaque thickened
oedematous corn ea
cata ractous lens

shallow anterior '---'-"'"""'

cha mber

Fig. 8.6 Acute angle closure due to an intumescent cataractous lens. The eye is red with a hazy view of the anterior segment from corneal
oedema, with a fixed irregular semidilated pupil from iris infarction. The slit image shows the corneal oedema and a very shallow anterior
chamber. Some uveitis may be present because of ischaemia, and this must be differentiated from the larger accumulations of lens material
and macrophages seen with phacolytic glaucoma (see Fig. 8.49).
 A

anteriorly
normal anterior subluxed lens
chamber depth

Fig. 8.7 Slit-image photography of the left and right eye of this patient demonstrates a subluxed lens in the left eye. The anterior chamber
is shallow and further examination shows that the anterior lens surface is closer to the posterior corneal surface inferiorly than superiorly
occluding the pupil and producing pupillary block.

Fig. 8.8 Occasionally pupillary dilatation allows a subluxed lens to swing into the pupillary plane and block communication between the
posterior and anterior chamber. Careful positioning of the patient and the use of miotics usually allow the lens to be repositioned safely
until definitive treatment can be arranged which in this case is removal of the lens.
 PRETRABECULAR OUTFLOW OBSTRUCTION

cataractous
lens dislocated
into the anterior f-',+---'~~~--- lens dislocated
into the anterior 1----'~"-"";;.:..o: .:·:··'··:. ::::.:..-,;:::·.··
chamber
chamber

Fig. 8.9 Pupil-block glaucoma following traumatic anterior dislocation of the cataractous lens. The slit-image view demonstrates how the
pupil is completely blocked by the lens with the peripheral iris bowed anteriorly around the lens. Prolonged lens-cornea contact may result
in endothelial damage.

SECONDARY ANGLE CLOSURE WITHOUT PUPIL BLOCK

Angle closure may occur without pupil block in four ways:
Changes in the posterior segment that push the lens-iris
diaphragm forwards
2 Changes in the anterior segment that result in loss of the
anterior chamber and iris-trabecular contact with synechia!
closure
3 Small eyes
4 Cellular proliferation within the angle of the anterior
chamber resulting in iris-trabecular adhesions.
Angle closure from changes in the posterior segment
Tumours form the most important (although the least common)
group of conditions in the posterior segment that push the
lens- iris diaphragm forwards. Other conditions that may cause
an increase in the volume of the posterior segment include
choroidal effusions arising either spontaneously or secondary
to intraocular surgery, posterior scleritis, encircling bands used
in retinal detachment surgery and rarely even ciliary body
cysts. An increase in permeability following a breakdown
of the blood-retinal barrier may occur after panretinal
photocoagulation or central retinal vein occlusion and lead to
either a choroidal effusion or a volume increase of the posterior
segment pushing the lens-iris diaphragm forwards.
Fig. 8.10 A patient with a long-standing blind eye presented with
recent onset of pain, conjunctival oedema and anterior chamber
haemorrhage. Posterior segment ultrasonographic examination
showed a large choroidal melanoma. Hemisection of the
enucleated eye demonstrates a large haemorrhagic choroidal
melanoma together with an anteriorly displaced lens and loss of
the anterior chamber.

diffuse
.-.,...-...,.--, posterior scleritis

Fig. 8.11 Posterior scleritis may be associated with an annular choroidal effusion that causes the ciliary body to rotate forward about the
scleral spur and the iris- lens diaphragm to move forward to produce angle-closure glaucoma. Ciliary body detachment may result in a
normal or low lOP, even in the presence of angle closure. This photograph shows a red eye with diffuse anterior and posterior scleritis,
although many of these eyes are completely white with inflammation limited to the posterior sclera alone.

anterior
choroidal effusions

Fig. 8.12 A fundus painting of the same patient reveals an

annular choroidal effusion (see also Ch. 5).
 PRETRABECULAR OUTFLOW OBSTRUCTION

very shallow AC

lens

choroidal effusions
serous retinal
detachment

thickened sclera
Fig. 8.13 In less obvious
cases than the case illustrated,
such effusions are easily missed
unless the peripheral fundus is
inspected carefully under full
i ! mydriasis. B-scan
\ ultrasonography is very useful.
By courtesy of Ms M Restori.

peripheral anterior
chamber shallowing
retrolental mass

Fig. 8.14 Persistent hyperplastic primary vitreous can produce a

contracting fibrotic retrolental mass with forward rotation of the
ciliary body and lens-iris diaphragm pushing the iris forwards to
occlude the angle. The anterior chamber is often shallow in these
elongated ciliary
eyes making angle occlusion more likely. (Top left) T h is slit-image processes
photograph shows a shallow anterior chamber and retrolental
mass. (Top right) Following mydriasis elongated ciliary processes
can be seen being pulled into the mass. (Bottom right) Gonioscopy
demonstrates traction and elongation of the ciliary processes.
SECONDARY GLAUCOMA
Malignant glaucoma (ciliolenticular block or aqueous misdirection syndrome)
The term 'malignant glaucoma' was originally used to describe
this syndrome because the eye did not respond to, and appeared
to be made worse by, treatment with pilocarpine. It is used to
describe eyes with a very high lOP, absent or shallow anterior
chambers and a retrolenticular accumulation of aqueous humour
in the absence of pupil block. The most common cause of this
uncommon condition is drainage surgery on an eye with a
shallow anterior chamber although other forms of intraocular
surgery that decompress the anterior chamber can also cause it.
Surgery on the fellow eye may be followed by the same result.
The mechanism appears to be an obstruction to forward flow
of aqueous humour in the presence of a shallow anterior
chamber causing misdirection of aqueous into the posterior
segment with pooling in the vitreous gel. Aqueous misdirection
appears to occur because of a change in the anatomical
relationship between the peripheral vitreous and ciliary processes
with the latter rotating forward when the eye is decompressed so
that aqueous flows posteriorly. This causes the lens- iris
diaphragm to move forward to occlude the angle with central
shallowing of the anterior chamber.
The treatment for malignant glaucoma should initially be
topical atropine (to relax the ciliary muscle and pull the lens-iris
Post erior Shallow AC
Forward Forward
rotat ion movement
of ciliary of lens
diaphragm posteriorly) together with acetazolamide, beta-
blockers and hyperosmotic agents (to lower lOP, dehydrate the
vitreous and reduce its volume). Pilocarpine makes the situation
worse. Surgical treatment involves decompression of the
retrolenticular aqueous pool by pars plana vitrectomy combined
with perforation of the anterior hyaloid face and removal of the
lens.
For pseudophakic malignant glaucoma the treatment of first
choice. is YAG laser anterior vitreolysis and posterior
capsulotomy. This photodisruption may allow aqueous to
percolate from the loculated pools within the anterior vitreous
into the posterior chamber and thus relieves the block to aqueous
flow. However pars plana vitrectomy is often required as laser
vitreolysis may only provide a temporary solution. A process
similar to that described above can occur in eyes that are aphakic.
Ciliovitreal block can occur if adhesions exist between the
anterior hyaloid face and the iris; this may be difficult to
distinguish from aphakic pupil block. The diagnosis is confirmed,
however, if following YAG laser iridotomy the condition is not
resolved and vitreous is seen to be occluding the iridotomy.
Surgical or YAG laser rupture of the anterior hyaloid face is
curative in this condition.
Fig. 8.15 This diagram illustrates how aqueous
passes posteriorly and then pushes the lens- iris
diaphragm forwards .
shallow anterior
chamber in uninvolved nea r absent anteri or
(contralateral ) eye chamber in eye w ith
ma li gnan t glauco ma
Fig. 8.16 These two slit-lamp photographs of the anterior
segments of each eye of a patient demonstrate a shallow anterior
chamber in the right eye (left), whereas the left eye (right) has
virtually no anterior chamber. The left eye had recently undergone
a trabeculectomy followed by loss of the anterior chamber from
malignant glaucoma. It is worth using topical atropine in higher-
risk eyes at the end of filtration surgery to prevent this.
 PRETRABECULAR OUTFLOW OBSTRUCTION 2

Synechia! closure of the angle

The uveitic eye can develop PAS even if its angle is not narrow.
In severe anterior uveitis the angle may become bridged by fibrin
which draws the peripheral iris towards the trabecular meshwork.
PAS may also occur when the anterior chamber is shallow
enough to allow iris contact with the angle structures. Examples
are hypotony from a leaking wound, corneal perforation or
cyclodialysis cleft and chronic or intermittent apposition from
uncorrected pupil block; these are hastened by coincidental
inflammation.

0
Fig. 8.17 PAS (left) should be distinguished from fine strands from the anterior iris surface to the trabecular meshwork which may be
seen in normal eyes (right).

II

visible peripheral
anterior synechiae
\\ \\~
\ .,
\ ·-

Fig. 8.18 Slit-image and gonioscopic photographs demonstrate

the development of PAS in chronic uveitis. Although often
confined to the inferior angle such synechiae can extend
circumferentially. With sarcoidosis, trabecular granulomas
irregular peripheral
occasionally form as focal lesions around the circumference of the
anterior synechiae
angle and, if untreated, may produce small areas of PAS (see
Ch 10).
SECONDARY GLAUCOMA

irregular pupil
margin and
posterior synechiae

Fig. 8.19 In this eye the pupil is occluded by posterior synechiae. Chronic gross circumferential PAS occlude the angle probably as a
result of previous pupil block.

Small eyes

There are a number of ocular conditions in which the eye itself is
considerably smaller than normal (e .g . congenital high
hyperopia, nanophthalmos, mucopolysaccharidoses, congenital
syphilis). Glaucoma occurs frequently in these rare conditions
from crowding of the angle by the iris. Surgical iridectomy in
such patients who often have very shallow anterior chambers
preoperatively may actually precipitate malignant glaucoma and
is therefore contraindicated, as is filtration surgery. Laser
iridotomy is the preferred method of initial treatment in these
unusual cases.

Fig. 8.20 Nanophthalmic eyes have an axial length of less than 20 mm, a
small corneal diameter and a normal-sized crystalline lens that is
disproportionally large in a small eye. High hyperopia is the norm. They are
predisposed to angle closure glaucoma in early to middle age because of
crowding of the angle. In this patient B-scan ultrasonography confirms that the
axial length is short ( 15 .25 mm) and posterior sclera thicker than average ( 1. 94
mm). Congenital syphilis and mucopolysaccharidoses also predispose to small
eyes and increased risk of angle closure glaucoma.
By courtesy of M s M Restori.
 PRETRABECULAR OUTFLOW OBSTRUCTION

Cellular proliferation with angle closure

Different cell types may be responsible for abnormal cellular
proliferation within the angle of the anterior chamber angle
leading to obstructed aqueous outflow:
• neovascularization (e.g. rubeotic glaucoma)
• endothelium (e.g. iridocorneal endothelial (ICE) syndromes)
• epithelium (e.g. epithelialization of the anterior chamber).
Neovascularization (rubeosis) of the iris and angle with
accompanying fibrous tissue formation is the most common type
of cellular proliferation causing angle occlusion. It is seen most
frequently in diabetic patients or in eyes with an ischaemic central
retinal vein occlusion (see Ch. 14). Iris neovascularization may
occur less commonly with uveitis, ocular arterial insufficiency,
long-standing retinal detachment, intraocular tumours or
radiation retinopathy. In all of these conditions the stimulus for
neovascularization appears to be retinal hypoxia with the release
of vascular endothelial growth factor (VEGF) which stimulates
new vessel growth on the iris and in the angle. New vessels appear
initially around the pupil margin and in the angle. Contraction of
the fibrovascular tissue on the anterior iris surface produces the
fixed dilated pupil with ectropion uveae seen in the late stages of
the condition. New vessels in the angle are usually followed by
PAS formation, outflow obstruction and raised lOP follow.
The extent and rapidity of this process varies with the disease.
It typically occurs about 3 months after a severe retinal vein
occlusion and extensive retinal hypoxia (' 100-day glaucoma')
and occurs less rapidly in diabetic patients. During the process of
neovascularization there may be a massive breakdown of the
blood-aqueous barrier with inflammation in the anterior
chamber. The patient experiences severe pain in the eye and by
the time of presentation the lOP may have risen to very high
levels as a result of the development of PAS.

Rubeotic glaucoma

Fig. 8.21 In the early stages (left), neovascularization is seen around the pupil margin as a fine vascular network that does not have a
normal anatomical distribution. In an advanced case (right) there is florid neovascularization, corneal oedema and aqueous flare. Pain in
these eyes is often due to a combination of inflammation and raised lOP; both can be treated to some degree by topical mydriatics and
steroids. Trabeculectomy is rarely successful in such eyes but enucleation may often be avoided by transscleral diode cyclophotocoagulation
(cyclodiode) or implantation of an aqueous shunt.
SECONDARY GLAUCOMA

ang le neovascularization

Fig. 8.22 Differentiating neovascularization from dilated iris vessels can sometimes be difficult. (Left) Radial iris vessels might be
confused with normal vessels, but gonioscopic examination reveals typical circumferential neovascularization in the angle (right) .

ectropion uveae
neovascular c:~------------;;5:-.:====i ca used by t raction
membrane from neovascu lar
mem brane

iris stroma ~~~~~=j iris pigment

""""""'=' - - - - - - -- - - -- _ j epit helium

PAS occluding
Fig. 8.23 Histological examination of the iris in neovascular
angle
glaucoma demonstrates a neovascular membrane on the anterior
trabecula r iris surface pulling the iris pigment epithelium on to the anterior
meshwork surface (ectropion uveae). The angle is occluded by a neovascular
membrane with endothelial slide from the corneal surface creating
angle closure.

The iridocorneal endothelial (ICE) syndromes
Essential iris atrophy, Chandler's syndrome and the iris- naevus
(Cogan-Reese) syndrome all result from a primary disorder of
the corneal endothelium and are different morphological aspects
of the same disease process. ICE syndrome is unilateral and
sporadic; it occurs in early adulthood and is more common in
women. The basic defect appears to be a loss of cell contact
inhibition with corneal endothelial cell proliferation and
formation of a Des<;:emet's-like membrane spreading across the
angle and on to the anterior iris surface (see Ch. 6). A
demarcation line may be seen on the cornea between normal and
abnormal endothelium. Herpes simplex infection has been
implicated in the aetiology but antiviral therapy does not appear
to influence the disease process.
Chandler's syndrome is characterized by corneal endothelial
cell decompensation and glaucoma producing oedema and early
presentation with haloes. The degree of corneal oedema is
PRETRABECULAR OUTFLOW OBSTRUCTION 23!
usually disproportionate to the level of lOP although it is often
improved by reducing the lOP. The endothelium that has been
completely replaced assumes a 'hammered silver' appearance
(see Ch. 6). PAS and corectopia (eccentric pupil) are not major
features. The increase in lOP does not necessarily correlate with
the degree of synechia! closure as an open angle may still be
occluded by a subclinical ICE membrane.
The ms-naevus syndrome gives the impression of
heterochromia due to the presence of iris nodules which are
really foci of normal iris stroma protruding through a
constricting membrane of endothelial cells on the anterior iris
surface. Traction by this membrane produces ectropion uveae .
PAS are a characteristic feature. The increased lOP is usually
resistant to medical therapy and trabeculectomy usually fails due
to ingrowth of ICE membrane; implantion of a drainage device
offers the best prospect of longer-term lOP control.
ecce nt ric pu pil
visible anterior
synechiae
.stret ch atrophy
of th e iris
Fig. 8.24 'Essential iris atrophy' is characterized by unilateral
glaucoma, corectopia (eccentric pupil), pseudopolycoria and PAS.
Migration of endothelium on to the iris produces chronic traction
at that point and stretching and eventual hole formation on the
opposite side of the iris (pseudopolycoria) .
Fig. 8.25 In this patient the prominent feature is the pupillary
distortion by an ICE membrane. Less obvious is the iris stromal
thinning in the opposite quadrant.
By courtesy of Dr A JW Huang.
6 SECONDARY GLAUCOMA

iris holes
PAS

Fig. 8.26 This left eye with more advanced disease and
intractable glaucoma has had a drainage device implanted. There is
marked nasal pseudopolycoria due to the ICE membrane drawing
the iris temporally.

peripheral anterior
synechia

Descemetfs
membrane-like
materia l on anterior iri s pigment
iris surface L___ _ _ __ ___:::::__ _ _ _ _ ___J epit helium

Fig. 8.27 Histological appearance shows a surface membrane on the iris stroma with ectropion uveae and angle closure. The glaucoma is
usually much worse than would be anticipated by the gonioscopic appearances, reflecting subclinical changes in the angle elsewhere.

eccentric pupil

Fig. 8.28 This patient with Chandler's syndrome shows a

bullous keratopathy (a prominent feature of the syndrome)
together with corectopia and iris atrophy (both of which are less
marked than in essential iris atrophy). PAS tend to be less
extensive than in essential iris atrophy although the lOP may still
be raised.
 PRETRABECULAR OUTFLOW OBSTRUCTION 23

fibrotic membrane
on anterior iris
surface replacing
normal iris
architecture

'iris naevus'

Fig. 8.29 In the iris- naevus syndrome, iris atrophy is less obvious than in the typical case of essential iris atrophy but there is more
corneal oedema . The anterior surface of the iris is covered by a sheet of Desr;:emet's membrane-like material through which normal nodules
of iris tissue protrude. These have been mistaken for iris melanoma resulting in enucleation. Ectropion uveae is common. In this
photograph note the ectropion uveae together with loss of the usual appearance of the anterior iris stroma.

Epithelialization of the anterior chamber

Glaucoma may result from epithelial cells gaining entry into the
anterior chamber (epithelial downgrowth). Conditions within the
eye needed for epithelial ingrowth are a poorly closed anterior
segment wound or implantation of epithelial cell nests into the
iris stroma from injury or surgery. Should these conditions occur,
epithelial cells proliferate either as a sheet within the chamber or
as a slowly growing cyst. Epithelial cysts are generally more
benign but may convert to sheet-like downgrowth if inadequately
surgically excised. Either can cause angle closure and secondary
glaucoma. Sheet-like downgrowth progresses inexorably, first
circumferentially around peripheral cornea then across the angle
and iris before moving centrally toward the visual axis; eventually
it can affect all anterior segment structures, lens and vitreous,
and, in vitrectomized eyes, even the retina . If the wound is
leaking the eventual sealing by proliferating epithelium causes
intractable lOP elevation because epithelium occludes the angle.
Membranes that are excised tend to recur despite aggressive en
bloc excision and management is usually to control the lOP. This
usually necessitates implantation of an aqueous shunt.

site of
perforating injury

Fig. 8.30 In this example a large epithelial anterior chamber cyst has developed after a traumatic perforation at the limbus. Surgical
excision of this type of cyst carries a high risk of converting a self-limiting cyst to a more malign sheet-like ingrowth.
8 SECONDARY GLAUCOMA

i---=-++---'<----1 retrocorneal membrane epithelialization

surgical wound of iris su rface
corneal oedema

corneal wound

Fig. 8.31 In this patient sheet-like epithelial downgrowth has occurred after a secondary intraocular lens implantation to produce a
retrocorneal membrane (left) and a membrane on the anterior iris surface (centre). A positive Seidal test is seen at the limbus (right).
By courtesy of Dr WW Culbertson, Bascom Palmer Eye Institute, University of Miami School of Medicine.

epithelial cell s
lining angle of
anterior chamber

Fig. 8.32 Histological examination shows occlusion of the angle

by direct spread of epithelial cells over the cornea, inner surface of
the trabecular meshwork and iris.
 TRABECUlAR OUTFlOW OBSTRUCTION: SECONDARY OPEN ANGlE GLAUCOMA
Trabecular meshwork function may be reduced by:
• Injury
• Occlusion by cells or other material
• Uveitis and steroid treatment.
ANGLE INJURY
A blunt injury to the eye compresses the globe and produces a
shockwave that is transmitted posteriorly through the eye. This
can tear the anterior face of the ciliary body to displace the iris
root posteriorly and appears gonioscopically as a broadened
ciliary band (angle recession). Associated hyphema is common.
Pathologically, the longitudinal and circular fibres of the ciliary
muscle are separated, with the longitudinal fibres remaining
attached to the scleral spur. With more severe force the ciliary
muscle may also disinsert from the scleral spur and be seen
gonioscopically as angle widening with cleft formation between
the scleral spur and ciliary band (cyclodialysis cleft). Angle
recession or cleft formation are common after blunt trauma.
Angle recession may be the only visible sign of a previous
contusion injury or may coexist with other signs of ocular injury.
Within the anterior segment these include iris sphincter rupture,
lens subluxation and dislocation and within the posterior
segment, commotio retinae, choroidal rupture and retinal
dialysis.
Early-onset glaucoma after a contusion is usually related to
concurrent uveitis or hyphema. A cyclodialysis cleft initially
causes hypotony because it facilitates aqueous outflow by the
uveoscleral pathway while aqueous secretion is disrupted. Its
subsequent closure, however, produces an acute and marked
increase in lOP. Eyes sustaining a marked angle recession or
anterior segment disruption at the time of initial injury have a
significant risk of developing cataract or secondary open-angle
glaucoma years after the event; this has important medicolegal
implications.
Fig. 8.33 Traumatic hyphema seldom results in significant lOP
increase in Caucasian eyes but lOP can rise dramatically in black
patients with sickle cell trait as the erythrocytes sickle in the
anterior chamber due to metabolic acidosis and clear very slowly. It
is worth remembering that angle recession is common in these
patients who may later develop secondary open-angle glaucoma.
angle recession
appearance of
normal trabecular f--'-;4~'<-\\ <'',:,
meshwork
Fig. 8.34 Gonioscopy in angle recession can demonstrate
widening of the ciliary band (iris root) or occasionally, following a
complete tear of ciliary muscle, widening of the angle together with
exposure of a white strip of sclera. These goniophotographs show
the angle in both the normal (left) and the involved (right) eye.
SECONDARY GLAUCOMA

Fig. 8.35 (Left) Angle recession is combined with full-thickness tears in the peripheral iris, through which the ciliary body is seen.
(Right) A segment of iris is completely separated from its root resulting in an iridodialysis and exposure of the ciliary processes.

r-------:::::==;;;;;;;;::::::::==:::::=-1 cyclodyalisis
cleft
:::~ cornea
d~,-------, cyclodialysis ciliary body
"'o cleft

Fig. 8.36 If the ciliary band (and hence ciliary body) detaches from sclera, a pathway (cyclodialysis cleft) is opened for aqueous to flow
from the anterior chamber to the suprachoroidal space. (Left) This results in chronic hypotony, often with maculopathy, and loss of vision.
Spontaneous closure of a cleft is not infrequent and if this occurs lOP may then rise precipitously. (Middle) Cyclodialysis clefts can
sometimes be difficult to see; gonioscopy and high resolution ultrasonic biomicroscopy is extremely useful in identifying their presence. By
courtesy of Prof D Reinstein. Chronic hypotony requires surgical closure of the cleft. (Right) Cyclodialysis cleft viewed during surgery from
the suprachoroidal space.
 . TRABECULAR OUTFLOW OBSTRUCTION: SECONDARY OPEN ANGLE GLAUCOMA
TRABECULAR MESHWORK OCCLUSION BY CELLS OR OTHER MATERIAL
Excessive or chronic exposure of the trabecular meshwork to
pigment, pseudoexfoliation material or cells can result in reduced
outflow facility. Clogging of the trabecular meshwork appears to
be the mechanism of lOP increase in eyes with severe hyphema,
ghost cell glaucoma after vitreous haemorrhage, phacolytic
glaucoma and Schwartz syndrome following retinal detachment
(clogging by retinal photoreceptor outer segments).
Pigmentary glaucoma
Pigment dispersion syndrome (PDS) is a descriptive term for the
deposition of pigment granules derived from the pigment
epithelium of the iris onto the structures within the anterior
chamber. Thus pigment may be found on the anterior iris
surface, the corneal endothelium (Krukenberg's spindle) or the
trabecular meshwork (as a midtrabecular band of pigment); less
frequently pigment is seen on the lens equator and zonules
following mydriasis. The pigment release occurs from abrasion of
the posterior iris surface by zonular fibres; for this to happen, the
midperiphery of the iris must be concave posteriorly. This
concavity occurs most often in young adult myopic males with a
deep anterior chamber. It is hypothesized that accommodation
produces a relative negative pressure in the posterior chamber
that makes the iris bow backwards resulting in 'reverse pupil
block'. Posterior iris bowing is often visible on gonioscopy.
Iridozonular contact and abrasion produce radial slit-like defects
in the pigment epithelium which are visible on iris
transillumination. The defects may disappear with time if
abrasion stops. If sufficient pigment is released to compromise
outflow facility the lOP rises (PDS with ocular hypertension); if
this persists for long enough glaucoma develops. Reduced
trabecular outflow results from chronic loss of trabecular cells
with phagocytosed pigment. Large dispersions of pigment occur
(pigment storms) can produce swings in lOP.
Treatment with miotics may reduce pigment shedding,
although these drugs are not well tolerated by young myopic
patients. Peripheral iridotomy can prevent the reverse pupil block
and may arrest the process but by the time the lOP becomes
raised irreversible trabecular damage has usually occurred and
the lOP remains increased. It can be lowered by conventional
treatment; approximately one-third of patients eventually require
filtration surgery.
An uncommon form of acquired pigmentary glaucoma has
been seen with posterior chamber intraocular lens implants
where the haptics rub against the posterior iris surface producing
pigment release.
circumferential
pigment deposition
on the anterior
iris surface
Fig. 8.37 In this patient extensive pigment deposition rather like
dust particles, is seen on the anterior iris surface lying in the
wrinkles formed by iris contraction.
~"---.,-1
. pu pil margin
.,:;
"\)
Fig. 8.38 Retroillumination of the iris of the patient in Fig. 8.37
shows multiple slit-like defects in the pigment epithelium of the
peripheral iris. Care must be taken in diagnosing pigmentary
glaucoma as a number of other conditions also cause peripheral
iris transillumination defects.
ECONDARY GLAUCOMA

pigment deposit on
0'-+--+-.....;::,-----l posterior corneal surface
(Krukenberg's spindle)

Fig. 8.39 Krukenberg's spindle is the term given to pigment

deposition on the posterior corneal surface. The pigment is usually
deposited in a vertical band.

Fig. 8.40 The angle in PDS is heavily pigmented often through

360°.

posterior bowing
of the iris

Fig. 8.41 The likely mechanism of pigmentary dispersion is abrasion of the peripheral
iris pigment epithelium by the anterior zonules which come into contact during episodes
of reverse pupil block induced by accommodation in some young myopes. This results in
backward bowing of the peripheral iris.
 TRABECULAR OUTFLOW OBSTRUCTION: SECONDARY OPEN ANGLE GLAUCOMA 2

cornea

canal of
Schlemm

Fig. 8.42 Histological section showing extensive pigment accumulation in the

angle. Pigment granules lie freely between the trabecular plates and are
phagocytosed within the endothelium or by macrophages. Loss of trabecular
endothelial cells results with collapse of normal trabecular meshwork architecture.

intrace llular
pigment

Fig. 8.43 Electron micrograph of the angle demonstrates a

characteristic accumulation of intertrabecular and intracellular
pigment granules that is not seen in age-matched control eyes.

Pseudoexfoliation glaucoma {exfoliation syndrome)

The term pseudoexfoliation has been used to distinguish this
condition from true exfoliation of the lens capsule seen following
exposure to infrared light (Glassblowers' cataract), although the
latter is extremely rare. Pseudoexfoliation is the descriptive term
given to dandruff-like material found on the pupil margin, the
anterior lens surface and occasionally the posterior corneal
surface. Despite its commonly cited propensity in Scandanavian
races pseudoexfoliation has been recorded in virtually every
ethnic group. The abnormal material is a glycoprotein derived
from a wide range of cells in the anterior lens capsule, the zonules
and the inner layer of ciliary epithelium as a result of a
generalized basement membrane disorder. Ultrastructurally,
pseudoexfoliative material comprises fine fibrils in a matrix. If
sufficient material is produced, the outflow facility may be
compromised and the lOP increased with eventual glaucoma.
The condition is usually bilateral, although asymmetrical. The
response to topical glaucoma medication is often poor.
Patients with pseudoexfoliation are usually elderly and have
coexistent cataract. Surgical treatment in these patients can
usefully be combined with cataract extraction. However, care
needs to be taken with cataract surgery because the zonules are
weak in these eyes.
Fig. 8.44 In pseudoexfoliation, exfoliated material abraded by
the iris from the anterior lens surface collects on the pupil margin
where it looks like dandruff. Pigment is also rubbed off the
posterior surface of the peripupillary iris and is deposited on the
anterior iris surface and in the iridocorneal angle. This eye also
shows widespread pigment deposition on the anterior iris surface.

clear zone

Fig. 8.45 Pupillary abrasion creates a characteristic zon e free of

pseudoexfoliative material. With further mydriasis the abnormal
material can be seen on the anterior lens surface.

Fig. 8.46 Extensive pigment deposition can be seen in the angle.

 TRABECULAR OUTFLOW OBSTRUCTION: SECONDARY OPEN ANGLE GLAUCOMA

/
~
,
I

~
~I

iris pigment
epithelium
iris

pigment
pseudoexfoliative deposition

material l;~!~~~~~~~~~~~~~ lens ca psule

lens
- -----"--- - ---1 material
pseudoexfoliative

Fig. 8.47 Histological appearance shows eosinophilic pseudoexfoliative material on the anterior lens capsule and posterior surface of the
iris. The angle contains more pigment than usual together with the fibrillar material caught up in the meshwork. This material can also be
found histologically around the conjunctival vessels.

fibri llar material

trabecu lar r---7'==->-

plates

Schlemm's cana l

Fig. 8.48 Electron microscopy reveals the

characteristic fibrillar material in the intertrabecular
spaces.
By courtesy of Professor D H Johnson
SECONDARY GLAUCOMA

Lens-induced glaucoma (phacolytic glaucoma)

The lens capsule of a hypermature cataract may leak denatured
cortical material. This is particularly common with Morgagnian
cataracts which should be removed to forestall this complication
(see Ch. 11) . Leakage in turn excites a macrophage response; the
macrophages, gorged with lens material accumulate and clog the
trabecular meshwork causing a secondary open-angle glaucoma
known as phacolytic glaucoma. Much more common today is
'lens fragment-related glaucoma' in which retained fragments of
lens nucleus after cataract surgery cause increased lOP after
surgery. Retained fragments should be carefully looked for in
these eyes with gonioscopy especially in the inferior angle where
they may be missed and offending lens matter should be
removed.

Fig. 8.49 Histological examination demonstrates lens-filled macrophages obstructing the angle and trabecular meshwork. Low
magnification (left) and higher magnification (right) of lens-filled macrophages. Clinically these are seen as large accumulations floating in
the anterior chamber of an eye with a mature cataractous lens and acute glaucoma, an open angle and a deep anterior chamber.

~- · , ,_

~__2,0 ,
~

Fig. 8.50 Retained fragments of lens nucleus or cortex from

complicated cataract surgery can cause an intractable increase in
lOP and recurrent inflammation. Here, a fragment of cortex is
visible in the inferior angle, even without gonioscopy. Removal of
retained cortex usually improves control of both the lOP and
intraocular inflammation.
TRABECULAR OUTFLOW OBSTRUCTION : SECONDARY OPEN ANGLE GLAUCOMA 2

tHP+--....,.,+-+---1 silicone oil globules

held in viscoelastic

Fig. 8.51 This anterior chamber contains both viscoelastic and

silicone oil after combined cataract and vitreoretinal surgery. In the
upright position the silicone oil is prevented from rising to the top
of the anterior chamber by the retained viscoelastic. Here, it is
retained viscoelastic that is causing the increased lOP after
vitreoretinal surgery; its removal by anterior chamber washout
should improve lOP control.

emulsified
silicone oil

Fig. 8.52 A typical hyperoleum of emulsified silicone oil

following vitreoretinal surgery in an aphakic eye.

oil globules
..
inflammatory ••··~ •
ce llular infiltrate f-4---------=-.~~

iris pigment
epithelium

Fig. 8.53 Prolonged presence of emulsified silicone oil in the

anterior chamber can cause a destructive chronic giant cell
reaction in the angle structures.
By courtesy of Mr R Azaria.
 SECONDARY GLAUCOMA

Haemolytic glaucoma

Blood cells and their degeneration products may cause
secondary open-angle glaucoma. Under normal conditions
healthy red blood cells pass through the trabecular meshwork to
enter Schlemm's canal. If the trabecular meshwork becomes
clogged by these cells the lOP will rise. With a healthy angle
elimination of hyphema is followed by return of the lOP to
normal. Haemolytic glaucoma is caused by erythroclasts left after
the absorption of haemoglobin from red cells. The reduced
malleability of ghost cells renders them more difficult to remove
through the meshwork. It should be suspected when open-angle
glaucoma is discovered in an eye with a long-standing vitreous
haemorrhage and minimal uveitis with yellowish discoloration
within the anterior and posterior chambers, especially if it is
aphakic. Phase-contrast microscopy may be used to identify
these degenerate red blood cells (ghost cells) on aqueous tap.

trabecular I-=-- -"---.

meshwork

macrophages ghost cel ls

fi lled w ith l~r--~,.:::;:,.~...;.:..~ !

ghost cel ls

Fig. 8.54 The histological appearance of the trabecular meshwork in haemolytic glaucoma shows degenerated red blood cells (ghost
cells) on the trabecular spaces and within macrophages.
By courtesy of Professor I Grierson.

Siderosis

Siderosis results from the widespread deposition of iron Clinically eyes with siderosis demonstrate mydriasis,
throughout the eye diffusing from a retained ferrous ocular heterochromia and retinal degeneration with optic atrophy as
foreign body. Glaucoma occurs secondary to sclerosis of the well as raised lOP. The ERG shows specific changes depending
trabecular meshwork which is thought to be a direct toxic effect. on the degree of retinal damage.

heterochromia
(green iris)
normal iris

Fig. 8.55 The right eye of this patient shows evidence of

siderosis with brown-green discoloration of the iris from iron
deposition.
 TRABECULAR OUTFLOW OBSTRUCTION: SECONDARY OPEN ANGLE GLAUCOMA
Tumour infiltration
About 5 per cent of eyes with tumours develop glaucoma either
as a result of angle closure from forward movement of the
lens-iris diaphr agm (see Fig. 8 . 1 0), neovascularization or
invasion of the angle by tumour causing secondary open-angle
glaucoma. Less commonly, a malignant melanoma arising from
24!
Fig. 8.56 Histological examination shows iron deposition within
the meshwork and Schlemm's canal associated with loss of normal
trabecular architecture. There is a reduction in the number of
trabeculocytes together with trabecular collapse.
the iris root and ciliary body may invade the angle directly to
produce glaucoma. On very rare occasions 'melanomalytic'
glaucoma arises from trabecular obstruction by macrophages
engorged with melanin from a necrotic tumour.
iris melanoma
pigment deposit ion
in t rabecula r meshwork
Fig. 8.57 Gonioscopic view shows an iris melanoma occluding
the angle.
Fig. 8.58 Histological appearance shows infiltration of the
angle and trabecular meshwork by melanoma cells from an iris
melanoma.
SECONDARY GLAUCOMA
UVEITIC GLAUCOMA
Uveitis has already been seen as a cause of pupil block (see Fig.
8.1). In addition it may cause chronic angle-closure glaucoma
from PAS (see F igs 8.17 and 8.18). Outflow facility may also be
reduced in uveitic eyes as a result of obstruction of an open angle
by inflammatory cellular debris or direct involvement of the
trabecular meshwork in the inflammatory process (trabeculitis) .
Two specific uveitic syndromes, the Posner- Schlossman
syndrome and Fuchs' heterochromic cyclitis, are also particularly
associated with open-angle glaucoma. Finally, topical steroid
Table 8.2 Mechanisms of lOP disturbance in uveitis
Increased lOP
Disease-related: Posner- Schlossman syndrome, herpes simplex,
herpes zoster, heterochromic cyclitis, juveni le chronic arthrit is
Iris bombe
Peripheral anterior synechiae
Trabeculit is
Cloggi ng by inflammatory cells
Steroid induced
Fuchs' heterochromic cyclitis (see also Ch. 10)
This chronic nongranulomatous uveitis is almost always
unilateral. Patients usually present complaining of floaters but
later vision is reduced as a result of cataract. Iris atrophy (the
affected iris has anterior stromal atrophy and a lighter colour)
and iris nodules, fine widespread keratic precipitates, cataract,
glaucoma and occasionally a fine neovascularization of the angle
treatment may induce an open-angle glaucoma. Table 8.2 lists
the mechanisms of lOP disturbance in patients with uveitis.
Because uveitis is symptomatic raised lOP tends to be
detected early often before there is overt damage to the optic
nerve. Optic disc asymmetry, especially in unilateral uveitis, is an
important sign even when the visual fields are normal. In young
patients increased disc cupping with very high lOP may be
partially reversible on lOP reduction.
Decreased lOP
Ci liary body inflammation
Choroidal effusion
Cili ary body detachment by tractional membranes
Cilia ry destructi on
Retina l detachment
are all seen in established cases (see Ch. 10). Neither anterior nor
posterior synechiae develop . The glaucoma responds to
conventional medical or surgical treatment and the eye responds
well to cataract surgery should it be indicated. The uveitis
responds poorly to steroids.
Fig. 8.59 A patient with heterochromic cyclitis of the right eye.
The affected iris is depigmented and a cataract is present.
 TRABECULAR OUTFLOW OBSTRUCTION: SECONDARY OPEN ANGLE GLAUCOMA 251

Fig. 8.60 Iris depigmentation and transillumination is seen with long-standing cyclitis. The keratic precipitates in Fuchs' heterochromic
cyclitis look unusual; typically they are distributed across the entire corneal surface and are often interconnected by a fine network of
filaments .

Posner-Schlossman syndrome {glaucomatocyclitic crisis)

This unusual condition is typically seen in young adult men who
develop very high levels ofiOP with minimal anterior uveitis that
is self-limiting. The syndrome is usually uniocular. Patients
present with blurring and haloes from corneal oedema due to an
lOP in the 40- 60 mmHg range. The uveitis is minimal and
typically only one sentinel keratic precipitate or, at most, a small
number of keratic precipitates are visible. Posterior synechiae do
not form. Occasionally, after many attacks, chronic increase in
lOP occurs from permanent damage to the meshwork either
directly from the disease process or secondary to raised lOP
causing degenerative changes in the meshwork. Whatever the
mechanism, a condition clinically indistinguishable from primary
open-angle glaucoma develops. Acute attacks typically last for
days. Herpes simplex and secretion of prostaglandins have been
implicated in the aetiology.

Fig. 8.61 Sentinel keratic precipitates seen during the quiescent

phase. There is some evidence that the increased lOP is associated
with high levels of aqueous humour prostaglandins.
- ------------------------------
SECONDARY GLAUCOMA
Steroid-induced glaucoma
Chronic topical steroid usage causes raised lOP in a proportion
of patients. There is some evidence that the steroid response in
this population is determined genetically and may be similar to
those in patients at risk of primary open-angle glaucoma,
possibly by stressing an already compromised angle . The
glaucoma usually appears after a few weeks of treatment and this
complication must be taken into consideration in any patient on
topical steroid therapy. In most cases lOP falls to normal on
cessation of the topical steroid. Different steroid preparations
vary in their ability to produce this phenomenon; the degree of
response is related to their potency and penetration of the cornea
and to their potential for hydrolysis within the aqueous humour.
The exact mechanism is uncertain but it is known that
glucocorticoids influence cell size, behaviour and cytoskeletal
organization, extracellular matrix turnover and composition of
the trabecular meshwork. Meshwork cells exposed to steroids
produce myocilin which is encoded by the gene GLCJA,
mutations of which are responsible for most cases of autosomal
dominant juvenile open-angle glaucoma. Histologically,
intertrabecular spaces are blocked by a fibrillar material.
bilateral
glaucomatous
cupping
Fig. 8.62 Glaucomatous cupping, more advanced on the left
than in the right, is seen in this patient who had used topical
steroids without supervision for treatment of mild ocular irritation
associated with contact lens wear.
fib ril lar material
Fig. 8.63 Electron micrograph of the corneal scleral meshwork
in a patient with steroid-induced glaucoma showing the
intertrabecular spaces filled with fibrillar material. In some areas
the trabecular lamellae are not completely covered with endothelial
cells.
Courtesy of Professor E Lutjen-Drecoll.
 POST-TRABECULAR OUTFLOW OBSTRUCTION: RAISED EPISCLERAL VENOUS PRESSURE

POST-TRABECULAR OUTFLOW OBSTRUCTION: RAISED EPISCLERAL VENOUS PRESSURE

Raised episcleral venous pressure is usually caused by a shunting ·
of arterial blood to the orbital veins by a caroticocavernous
fistula, but is occasionally seen with gross cor pulmonale, the
Sturge- Weber syndrome or superior vena cava obstruction. An
increase in episcleral venous pressure reduces the pressure
gradient required to maintain conventional trabecular aqueous
outflow and therefore an increase in intraocular pressure results.
With fistulae between the carotid artery and cavernous sinus
where the shunt is usually of high flow, the diagnosis is
sometimes obvious from the dramatic neuro-ophthalmic signs
(see Ch. 20). However, coexistent ocular ischaemia complicates
this picture and even in the presence of rubeosis iridis (which is
not infrequently present in these eyes) the lOP may be low. In
contrast, arteriovenous communications within the dural vessels
are frequently of a low-flow type; these patients present with red
eyes, arterialized conjunctival vessels and glaucoma without the
other overt signs of bruits or proptosis. Apart from glaucoma,
these dural shunts usually have a benign prognosis and may
resolve spontaneously. The glaucoma may vary in severity;
patients with high lOP respond poorly to medical treatment.

Fig. 8.64 This patient presented with a red right eye with raised lOP. A helpful
diagnostic sign of a caroticocavenous fistula is an increased pulse amplitude due to the
A-V shunt which is observed when performing applanation tonometry.

Fig. 8.65 Arterialized vessels are seen in the conjunctiva.

engorged
retinal veins

normal fund us

Fig. 8.66 Retinal veins are engorged in the right eye although at
this stage the optic disc does not show glaucomatous changes. The
lOP in the left eye had an increased pulse amplitude. The patient
was found to have a dural caroticocavernous fistula that was
treated by embolization.
SECONDARY GlAUCOMA

Fig. 8.67 Grossly arterialized vessels are seen in another patient

with a long-standing dural fistula.

STURGE-WEBER SYNDROME

The Sturge- Weber syndrome presents with facial and
intracranial angiomas of variable degree. Glaucoma occurs in at
least 30 per cent of patients and possibly as high as 70 per cent.
It is said to be more common when the upper lid is involved.
About 50 per cent of patients present with buphthalmos within
the first 2 years of life but there is a lifelong risk of glaucoma.
Unilateral or marked asymmetrical ocular involvement is typical.
The condition responds poorly to medical treatment and surgery
for buphthalmos is commonly required in infancy, childhood or
early adult life. Filtration surgery may be extremely hazardous. If
a . coexistent choroidal haemangioma is found or suspected (see
Ch. 9), surgery should be performed under hypotensive
anaesthesia to minimize the risk of intraoperative choroidal
haemorrhage. The dissection of the scleral flap may be prejudiced
by angiomatous changes in the sclera; meticulous haemostasis is
required.

Fig. 8.68 This baby has a facial angioma involving the upper lid and maxillary area.
Both eyes were buphthalmic but the right eye was worse than the left. The child later
developed severe epilepsy from an intracranial angioma.
 POST-TRABECULAR OUTFLOW OBSTRUCTION: RAISED EPISCLERAL VENOUS PRESSURE 25

blood in
Sch lemm 's cana l

Fig. 8.70 Goniophotographs show blood in Schlemm's canal

because the normally outwardly directed pressure gradient is
reversed by the raised episcleral venous pressure.

Fig. 8.71 When planning surgery it is important to

look for choroidal involvement as these can bleed and
cause devasting haemorrhage when the eye is opened.
This colour Doppler B-scan ultrasonographic image
demonstrates blood flow within a choroidal
haemangioma in the region of the posterior pole.
By courtesy of Ms M Restori.
The Uveal Tract
Berti! Damato~ David Spalton

Normal Anatomy
Congenital Anomalies of the Uveal Tract
Tumours of the Uveal Tract
Iris Tumours
Choroidal and Ciliary Melanotic Tumours
Other Choroidal Lesions
8 THE UVEAL TRACT

NORMAL ANATOMY

The uveal tract is a pigmented, vascular layer lying between the
retina and sclera. It consists of the iris, ciliary body and choroid
lying in continuity with one another. Apart from the specialized
muscular structures of the iris and ciliary body, the uveal tract is
concerned with nutrition of the eye through the secretion of
aqueous humour by the epithelium of the ciliary body, and with
the maintainence of the outer retina from the choroidal
circulation.
Melanocytes, derived from the neural crest, contain melanin
in melanosomes and are scattered throughout the tract; there is
both an inter-individual and inter-racial difference in their
relative concentration which accounts for the colour of the iris
and the degree of fundus pigmentation. In contrast, the pigment
epithelium of the iris and retina is derived from the
neuroectoderm of the optic cup. Pigmentation appears here
(apart · from the inner layer of the ciliary epithelium, which
remains nonpigmented throughout life) at 6- 8 weeks of gestation
whereas pigmentation of the iris and choroid is not complete
until about 9 months of age.

THE IRIS

The iris controls the degree of retinal illumination through the
tone of the sphincter and dilator muscles which are under
parasympathetic and sympathetic neuronal control respectively.
The pigment epithelium on the posterior surface prevents entry
of extraneous nonaxial light and so refines the optics of the eye
(the absence of this may contribute to the poor visual acuity of
ocular albinos). The iris derives its blood supply from
anastomosis of the posterior and anterior ciliary circulations at
the major arterial circle which lies in the root of the ciliary body
and sends radial branches to the incomplete minor circle at the
level of the collarette. Blood vessels in the iris have tight
endothelial junctions and thick vascular walls to withstand
compression by iris dilatation.

THE CILIARY BODY

A precise knowledge of the poslt!on of the ciliary body is
important in the positioning of surgical incisions for vitreous
surgery. The surface markings of the ciliary body from the
corneal limbus are 1. 5-8 mm on the temporal side and 1. 5-7 mm
on the nasal side. The anterior third (2 mm) contains the ciliary
muscle and ciliary processes, and is known as the pars plicata.
The posterior two-thirds-the pars plana- extends posteriorly to
the ora serrata where it merges with the retina. There is a dense
attachment of the vitreous base over this area and on to the
anterior equatorial retina (see Ch. 12).
The ciliary muscle is triangular in transverse section and
controls accommodation. The outermost fibres run
longitudinally inserting into the scleral spur; more internally the
muscle fibres are radial with the innermost fibres running
circumferentially. Contraction of the external longitudinal fibres
transfers tension indirectly to the trabecular meshwork through
the scleral spur and may explain the mechanism ofiOP lowering
by pilocarpine.
Overlying the ciliary muscle the epithelium and stroma are
thrown up into about 80 ciliary processes. These have a vascular
stroma and are covered by two layers of epithelium which are
continuous with the iris pigment epithelium anteriorly and with
the retinal pigment epithelium and neurosensory retina
posteriorly. The inner or superficial epithelial layer is
nonpigmented and has tight intercellular junctions. Aqueous is
secreted through these cells (see Ch. 7). As in the choroid, the
capillaries in the ciliary processes are fenestrated.

Fig. 9.1 The iris consists of loose, pigmented vascularized tissue anteriorly and a double layer of pigment
epithelium posteriorly. The sphincter muscle lies towards the pupillary margin and the dilator muscle in close
relation to the pigment epithelium. About 1-2 mm from the pupillary margin on the anterior surface there is
a frill known as the collarette. This is the site of the embryological pupillary membrane which atrophies in
the eighth month of gestation, and of the minor arterial circle of the iris.
 NORMAL ANATOMY

ora serrata

long ci liary vessel

Fig. 9.2 A posterior view of the lens and anterior segment shows
the insertion of the retina into the pars plana at the ora serrata and
the ciliary processes of the pars plicata. A few remaining zonular
fibres can be seen supporting the cataractous len s.

major arteria l , - - - - ------nr---,--,

circle of iris -
pigmented
epitheli um
non-pigmented
epithelium
zonu lar fibres
ci liary stroma

ciliary muscle

Fig. 9.3 The ciliary body extends from the scleral spur to the ora serrata. Under higher magnification
the details of the pars plicata are seen more clearly. Note the two layers of ciliary epithelium, the
zonular fibres and the major arterial circle of the iris. At the ora serrata, the neuroretina becomes
attenuated and cystic, and terminates as the inner non-pigmented epithelium of the ciliary body.
The retinal pigment epithelium is continued as the outer pigmented epithelial layer of the pars
plana.
THE UVEAL TRACT
THE CHOROID
The lamina suprachoroidia is an area of delicate connective tissue
that forms a potential space immediately beneath the sclera. The
long ciliary vessels and nerves lie in this space and it is in this area
that choroidal effusions collect and the uveoscleral outflow of
aqueous humour occurs. The choroid has an extensive vascular
bed in which the larger vessels are the most external. The arteries
BLOOD SUPPLY OF THE UVEAL TRACT
The uveal tract, and especially the choroid, has an exceptionally
high blood flow; for this reason, only about 3 per cent of the
oxygen carried is extracted. The choroid supplies oxygen to the
retinal pigment epithelium and photoreceptors by diffusion.
Metabolites are transported through the pigment epithelium to
and from the retina by active transport processes.
The vascular supply of the uveal tract comes from the
posterior ciliary circulation anastomosing anteriorly with the
anterior ciliary arteries. The short posterior ciliary arteries leave
the ophthalmic artery posteriorly in the orbit (see Ch. 20) and
run forwards to penetrate the sclera circumferentially around the
optic disc, usually in two major horizontal trunks that divide to
supply the optic disc, retrobulbar optic nerve (see Ch. 17) and
the choroid. At the disc, two long posterior ciliary branches from
these run forward medially and laterally in the lamina
Anterior
conjunct iva l vessels
Retina - - +--1\\lllll.l
Choro id - - ----\----\\'10..'-\
Sclera ---~
:._,tJ~--
"">"i\-~----
are short and of large calibre, and give rise to a network of
fenestrated capillaries-the choriocapillaris- that lies directly
under Bruch's membrane and supplies the vascular needs of the
outer retina through the retinal pigment epithelium. The stromal
tissue contains melanocytes, collagen fibres and lymphocytes.
Fig. 9.4 The normal choroid is a highly vascular tissue . Its
macroscopic appearance is black owing to pigmentation from
stromal melanocytes. In this histological section the retina is
artefactually detached.
suprachoroidia to anastomose with the anterior ciliary arteries
adjacent to the major circle of the iris. These long posterior ciliary
arteries can frequently be seen in the horizontal meridians of a
normal eye if the retinal pigmentation is not too dense. The
anterior ciliary arteries are also derived from the ophthalmic
artery. They lie on the external ocular muscles (two arteries on
the medial, inferior and superior recti, and one on the lateral) and
penetrate the sclera at the muscle insertions, and may contribute
to the supply of the iris, ciliary body and anterior choroid
(although under normal circumstances in a healthy eye the flow
is retrograde). The choroidal venous return drains into the orbital
veins by the vortex veins, of which there is usually one, but
sometimes two, lying in each quadrant of the sclera at the
equator.
Major arterial circle of iris
Anterior ciliary vessels on
external ocular muscle
Fig. 9.5 Diagram showing the vascular
Long posterior
ci liary artery
supply of the choroid by the anterior and
posterior ciliary circulations. (Further details
Short posterior
ciliary arteries of the anterior ciliary and conjunctival
circulations are described in Chapter 5 and
the optioc disc in Chapter 17.)
 NORMAL ANATOMY

endothelial Bruch's
cell membrane

Fig. 9.6 The choroidal arteries divide rapidly to form the

choriocapillaris lying beneath Bruch's membrane. These
capillaries have fenestrations between the endothelial cells
allowing plasma to leak into the extracellular space. Although
there are anatomical anastomoses between the choroidal
vessels, physiologically the choriocapillaris functions on a
lobular basis.

delayed
choriocapillaris H-J...--f'-..)~
filling

retinal vein

Fig. 9. 7 Clinically this is demonstrated in the earliest phases of a

fluorescein angiogram as patchy delayed filling of the choroidal
bed, and is seen as choroidal infarcts such as Elschnig's spots or
Siegrist streaks (see Ch. 14).

'fof---1-ff"'t--t-/H ch or ioca piII aris

::--"•+"-"'""1--7-;~'-1 choroidal vein

Fig. 9.8 A digest preparation of a cast viewed from the choroidal side in the vicinity of the optic disc shows choroidal arteries supplying
the choriocapillaris and drained by the choroidal veins.
By courtesy of Miss J Olver.
THE UVEAL TRAcr

uniform
ca pill ary pattern

Fig. 9.9 These digest casts of the human choroid show the choriocapillaris from the retinal aspect. At the posterior pole the pattern is
uniform (left), in the equatorial fundus a lobular pattern is more apparent (middle), and in the periphery large fan-shaped lobules can be
seen (right).
By courtesy of Miss J Olver.

CONGENITAL ANOMALIES OF THE UVEAL TRACT

COLOBOMAS

Colobomas result from defects of closure of the optic cup that found inferonasally and may involve the iris, choroid and retina,
occur at 7- 8 weeks of fetal life. They can present as a sectorial or optic disc (see Ch. 17).
deficiency varying from the trivial to the gross. They are typically

Fig. 9.10 Iris colobomas are sometimes associated with

segmental absence of the lens zonules causing a localized
indentation of the lens and usually with defects in the choroid and
retina. This child with bilateral iris colobomata also has a poorly
sighted divergent left eye due to a large chorioretinal coloboma
involving the macula.
 · · · occurs either as a familial autosomal dominant disease
sporadically. The autosomal dominant condition is associated
glaucoma, nystagmus, corneal opacities and photophobia,
sporadic cases usually have a high incidence of
(Wilm's tumour). This is associated with
ALBINISM
Albinism results from a defect in the synthesis of melanin. There
are at least ten differently inherited forms of albinism; most
forms are inherited recessively and many types are extremely
rare. Albinism can be classified into oculocutaneous forms, in
which there is both eye and skin involvement and ocular forms,
in which hypopigmentation is limited to the eye. Ocular albinism
is usually X-linked. Oculocutaneous forms can be subdivided by
hair follicle analysis into those that have a complete absence of
pigmentation (tyrosinase negative) and those that are tyrosinase
positive. Tyrosinase-positive subjects can be more difficult to
diagnose; these patients usually have reddish or light brown hair
and paler skin pigmentation than other members of the family
although their pigmentation increases with age. All ocular albinos
have translucent irides on retroiiiumination. Purely cutaneous
albinos have no ocular complications.
Apart from increased ms transillumination and
hypopigmented fundi, albinos with ocular involvement have
congenital nystagmus, macular hypoplasia, a high incidence of
squint and amblyopia, and an anomaly of the chiasm in which
the majority of optic nerve fibres from each eye decussate. This
is thought to be caused by the absence of pigmented cells in the
Fig. 9.12 An oculocutaneous tyrosinase-negative patient with
congenital nystagmus and a right convergent squint. Note the
white eyelashes.
deletion of a tumour suppressor gene, which has been identified
on chromosome 11, analogous to the retinoblastoma gene on
chromosome 13. All such children require regular screening by
renal ultrasonography. A vestigial iris remnant can usually be
seen as a frill on gonioscopy (see Ch. 7) .
lens f-'-+-~!+-- r.~~~~ lens
on.----,,----, iris fril l
iris fri ll l -""":::~~::;..~~-1
Fig. 9.11 Retroillumination of the eyes of a child with aniridia
shows the lens and zonular gap. The iris remnant remains as a frill
that forms peripheral anterior synechiae to obstruct the angle
causing glaucoma usually in early adulthood.
By courtesy of Mr David Taylor.
chiasm during embryogenesis; these cells 'direct' the ingrowing
axons. Ocular albinism is a common cause of congenital
nystagmus and it is important to examine all such patients for
increased iris translucency by iris retroiiiumination. Excessive
pigmentation (melanosis oculi) is discussed in Chapter 3.
abn ormal
/ macular reflex
promin ent
equator of lens ...,.,f\R<- - - -I choro idal vessels
Fig. 9.13 Retroillumination of the iris through the pupil
demonstrates the gross lack of iris pigmentation. Fundus
photography in the same patient shows the lack of retinal and
choroidal pigmentation. Large choroidal vessels are clearly seen.
 TUMOURS OF THE UVEAL TRACT
The commonest primary tumours of the uveal tract are naevi and
malignant melanomas, which arise from melanocytes derived
from the neural crest. Other types of tumour, which are rarer, can
arise from blood vessels (haemangioma), nerves (neuri-
lemmoma), smooth muscle (leiomyoma), retinal pigment
epithelium (adenoma, adenocarcinoma), as well as the
IRIS TUMOURS
Naevi account for most tumours of the iris. These are more
common in lightly coloured eyes. They tend to be small (less than
4 mm in diameter) and less than 2 mm thick. Such tumours must
Fig. 9.15 The naevus is formed by proliferation of iris melanocytes which form a nodular layer on the anterior surface of the stroma.
nonpigmented and pigmented epithelia of the iris and ciliary
body (cysts, adenoma, adenocarcinoma, medulloepithelioma).
Other tumours of the uveal tract include metastases and
choristomas (i.e. normal tissue in an abnormal site, for example
osseous choristomas); tumours must be distinguished from
masquerading lesions such as haematomas and uveal effusions.
be distinguished from melanomas and from rare lesions such as
leiomyoma or from non-neoplastic lesions such as essential iris
atrophy, intraocular foreign body or iris heterochromia and cysts.
Fig. 9.14 Iris naevi may be pigmented or amelanotic, vascular or
avascular and bulky or flat. They may be associated with adjacent
ectropion uveae (which is not a sign of malignancy) and can
extend into the angle. Iris freckles do not distort normal iris
anatomy. Naevi may enlarge or become more deeply pigmented
after puberty. Iris naevi can be confused with the so-called
iris-naevus (Cogan-Reese) syndrome, a variant of the iridocorneal
endothelial (ICE) syndrome (see Chs 6 and 8).
iris pigment
epithel ium
 IRIS TUMOURS

Fig. 9.16 About 90 per cent of patients with neurofibromatosis

develop multiple hamartomatous naevi (Lisch nodules) on the
stromal surface by their teens. These can occur in both
neurofibromatosis types 1 and 2, although they are more common
in type 1 (see Chs 2 and 20).

Fig. 9.17 Melanomas of the iris may be clinically indistinguishable from naevi until growth can be demonstrated. Almost all are located
in the inferior iris. Colour photography is helpful to document the lesion. Fluorescein angiography is unhelpful in determining whether the
tumour is benign or malignant. Some melanomas are highly vascular and may mimic haemangiomas. If the tumour extends to the angle,
transpupillary transillumination may reveal ciliary body involvement although high-frequency ultrasound scanning is more accurate. In
some centres, local resection has been replaced by radiotherapy delivered with either an iodine plaque or proton beam. Although iris
melanomas have a relatively good prognosis compared with more posterior melanomas they should not be considered benign.

Fig. 9.18 Iris melanomas can be amelanotic.

THE UVEAL TRACT

tumour spreading
into ciliary body f----+
corneal
iris
reflections

Fig. 9.19 High-frequency ultrasound imaging is extremely useful in delineating the extent
of the lesion and documenting its size.

stroma replaced
by spindle cell ~"'--....,,-----\l:;c;-&-­
melanoma
blood vessel

Fig. 9.20 This iris is diffusely infiltrated by a low-grade spindle cell melanoma with extension on to the inner surface of the trabecular
meshwork.
By courtesy of Professor W R Lee.

Fig. 9.21 Cysts can arise from the posterior surface of the iris or ciliary body and may mimic a melanoma. If the edge of the cyst is not
visible at the pupil margin it can often be seen with a three-mirror lens after maximal mydriasis. High-frequency ultrasound scanning is
very useful to demonstrate the cystic nature of the lesion, its site and extent. Clear cysts arise from the nonpigmented ciliary epithelium,
whereas pigmented cysts originate from the iris pigment epithelium; these cysts may wobble on eye movement and are often multiple and
bilateral. They tend to cause cataract and may result in glaucoma. Rarely, implantation cysts lined by stratified squamous epithelium occur
within the iris stoma.
 CHOROIDAL AND CILIARY MELANOTIC TUMOURS

Fig. 9.22 Metastases to the iris are rare. They present as white or
pink tumours that grow rapidly, becoming irregular and
haemorrhagic. Most arise from primary neoplasms in lung or
breast.

Fig. 9.23 Juvenile xanthogranuloma has similarities to but is separate from the spectrum of Langerhan's histiocytic cell proliferative
disease. Iris lesions are rare, affecting children under 3 years of age who also develop typical orange skin lesions. Infants present with a
unilateral, raised, yellowish lesion on the iris with spontaneous hyphema. Vision may be lost from secondary glaucoma. Histological
examination shows a histiocytic infiltration of the iris that responds to steroids or radiotherapy.
By courtesy of Mr J J Kanski.

CHOROIDAL AND CILIARY MELANOTIC TUMOURS

Melanotic lesions are by far the most common type of choroidal melanomas can vary from complete amelanosis to a dense black
tumour. They can be divided into benign naevi and malignant lesion. Both naevi and melanomas are much less common in
melanomas. The amount of pigmentation in both naevi and racially pigmented eyes.
THE UVEAL TRACT

CHOROIDAL NAEVI

Fig. 9.24 Choroidal naevi occur in about 10-30 per cent of the Caucasian population and are usually detected after puberty. Most naevi
are small and flat with a slate-grey colour and the overlying retinal pigment epithelium shows minimal secondary change.

Fig. 9.25 A small proportion of choroidal naevi are relatively bulky and therefore induce degenerative changes in the overlying retinal
pigment epithelium, similar to those caused by melanomas. Clinical features indicative of a benign nature are a tumour thickness of less
than 2 mm, the presence of hard drusen on the surface, the absence of clumps of 'orange pigment', and the absence of a serous retinal
detachment over the tumour. Such signs are not reliable indicators, however, and suspicious naevi should be monitored for growth
comparing the ophthalmoscopic appearances with a baseline colour photograph. The patient should be seen after 3-4 months and then 6
monthly and eventually once a year. Such monitoring should be lifelong because malignant growth can occur after many years of apparent
inactivity.

CHOROIDAL MALIGNANT MELANOMA
The incidence of uveal melanoma is about 5 per million per year
in adult Caucasians. The incidence increases with age, reaching a
peak in the sixth and seventh decades of life. Over 90 per cent of
all uveal melanomas arise in the choroid, with 3 per cent
originating in the ciliary body and 3 per cent in the iris.
Most patients with choroidal melanomas present with blurred
vision, visual field defect, photopsia and metamorphopsia. The
visual symptoms can be caused by the tumour itself or by
secondary effects such as exudative retinal detachment, cataract
and astigmatism. It is not unusual for an asymptomatic tumour
to be detected on routine examination. Rarely, uveal melanomas
present with glaucoma, uveitis or as a cosmetic blemish on the
sclera. Vitreous haemorrhage is unusual and is more likely to be
CHOROIDAL AND CILIARY MELANOTIC TUMOURS
choriocap illaris
"''\,........ ~....,.,., choroid
-----.!=5--"'"""1 heavily pigm ented
melanocytes
Fig. 9.26 The choroid is slightly thickened by a proliferation of
heavily pigmented melanocytes. The choriocapillaris is spared and
the histological features are those of a choroidal naevus.
caused by other conditions. Melanomas can present with
rubeosis and secondary glaucoma in a blind cataractous eye.
The ophthalmoscopic appearances depend on the degree of
pigmentation and whether or not the tumour has ruptured
Bruch's membrane and the retinal pigment epithelium. The large
majority of uveal melanomas are readily distinguished from other
tumours on examination by indirect ophthalmoscopy or
biomicroscopy. Rarely, histological confirmation of the diagnosis
is required . In such cases, a transvitreal fine-needle aspiration
biopsy is usually performed, although in some centres trans-
scleral biopsy is preferred. The differential diagnosis of ciliary
body tumours is often difficult, and in these patients local
excision achieves both a diagnosis and a cure.
Fig. 9.27 Ophthalmoscopically, abnormal deposits of lipofuscin
accumulate over the surface of the tumour ('orange pigment').
THE UVEAL TRACT

Fig. 9.28 This patient has a large malignant choroidal melanoma

that has not broken through Bruch's membrane.

RPE proliferation
and multilayering

Fig. 9.29 The degree of pigmentation in uveal melanomas varies

greatly even within the same tumour, but this cannot always be
properly appreciated clinically unless the overlying retinal pigment
epithelium is atrophic or absent. Melanomas may have tapering
margins where the overlying retinal pigment epithelium is still
relatively healthy; therefore, unless the tumour is deeply
pigmented, such lateral extentions may be clinically invisible.

tumour vessels

amelanotic
'collar stud' ~f#it---'i'"""'~"'
tumour

Fig. 9.30 This is an amelanotic collar-stud melanoma with engorged tumour blood vessels. These are usually visible ophthalmoscopically
only if the tumour has ruptured the retinal pigment epithelium and is nonpigmented. The pigmented base of this collar stud tumour is due
to multilayering of the retinal pigment epithelium and not to melanin in the tumour.
 CHOROIDAL AND CILIARY MELANOTIC TUMOURS

'collar stud' extension

choroidal base
rupture of
Bruch's membrane

Fig. 9.31 Choroidal melanomas are moulded into a smooth dome by the overlying Bruch's membrane and retinal pigment epithelium.
When the tumour ruptures these layers it herniates into the subretinal space. The edge of the break in Bruch's membrane strangulates the
blood vessels in the prolapsed part of the tumour so that they become engorged, also leaking fluid. The herniated part of the tumour
becomes globular so that the melanoma develops a mushroom shape (also described as 'collar-stud' or 'dumb-bell').

serous retinal
detachment

diffuse flattish tumour

Fig. 9.32 A small proportion of choroidal melanomas infiltrate

the uvea without forming a bulky tumour. Such 'diffuse'
melanomas tend to be highly aggressive and have often extended
extraocularly by the time they are diagnosed.

Fig. 9.33 The episcleral blood vessels overlying a large ciliary

body tumour tend to become dilated and tortuous and may be
mistaken for episcleritis. Such 'sentinel vessels' can occur with
benign tumours and are not necessarily a sign of malignancy.
THE UVEAL TRACT

Fig. 9.34 Choroidal

melanomas, and indeed other
tumours, tend to cause
secondary degenerative
changes in the overlying tissues
that influence their
ophthalmoscopic features. The
choriocapillaris is eventually
totally destroyed. The retinal
pigment epithelium becomes
multilayered in some areas and
atrophic in others, and
multiple small pigment
epithelial detachments may
develop over the tumour.

melanoma
Fig. 9.35 If the retinal pigment epithelium is still present over a
melanoma, drusen and small pigment epithelial detachments will
appear as hyperfluorescent spots. When fluorescein diffuses from
the residual choriocapillaris and tumour vessels through defects in
the retinal pigment epithelium, there is diffuse late hyper-
fluorescence as the dye accumulates in the subretinal space. In
comparison to fluorescein angiography, indocyanine green
angiography provides more information about tumour extent and
vascularity deep to the retinal pigment epithelium.

im:i-7'----1 hyperfluorescent tumour

blood vessels

Fig. 9.36 If the melanoma is exposed to view because Bruch's membrane is ruptured or the retinal pigment epithelium is absent or
atrophic, the angiographic appearances depend on the degree of pigmentation. An amelanotic collar-stud tumour is hyperfluorescent and
large choroidal vessels are visible near its surface.
 CHOROIDAL AND CILIARY MELANOTIC TUMOURS

choroidal RPE atrop hy

hypofluorescence
dense ly pigmented
'collar stud' extension ~..:::O....:I--1 'co ll ar stud' extension

Fig. 9.37 This deeply pigmented collar-stud melanoma has broken through retina as well as Bruch's membrane and retinal pigment
epithelium. The angiogram shows how the tumour itself is totally nonfluorescent. The surrounding hyperfluorescence arises from drusen
and subretinal fluid over abnormal retinal pigment epithelium anterior to the tumour and from the sclera where the retinal pigment
epithelium and choroid are atrophic.
Reproduced w ith permission of Eye.

Fig. 9.38 Transpupillary transillumination will help to distinguish pigmented from nonpigmented tumours. Not all pigmented tumours
are melanomas, however, and conversely not all melanomas are pigmented. Transpupillary transillumination gives an approximate
indication of the extent of a pigmented tumour. Care must be taken not to be misled by oblique illumination of the tumour or by an
adjacent subretinal haematoma.
 E UVEAL TRACT

co llar stud extrusion

~"¢"
---.~-.--+-dome-shaped
melanoma

rupture of
Bruch's membrane

Fig. 9.39 When making a diagnosis or planning therapy, A and B scan ultrasonography (see Ch. 1) are essential for measuring the
dimensions and defining the extent of the tumour. Ultrasonography can help to identify extraocular exten sion before surgery and to
confirm or exclude the presence of a tumour when the ocular media are opaque. Melanomas tend to have a highly reflective surface with a
low internal acoustic reflectivity; this helps to distinguish them from haemangiomas and secondary neoplasms which have high reflectivity.
Rare nonmelanomatous uveal tumours such as leiomyoma can be indistinguishable from melanoma. A collar-stud configuration is almost
pathognomonic of melanoma.

high tumour
low tumour signal signa l

Fig. 9.40 Melanin has shortT! and T2 relaxation times so thatTl -weighted images are relatively hyperintense and T2-weighted images
are hypointense compared with vitreous on MRI. These characteristic paramagnetic features may be helpful in distinguishing melanoma
from other conditions (e .g. metastasis, haemangioma and haematoma) . It must be remembered, however, that other tumours (e.g.
melanocytomas, adenocarcinomas and leiomyomas) can contain melanin which may confuse the result.
By courtesy of Dr Nigel McMillan.
 CHOROIDAL AND CILIARY MELANOTIC TUMOURS

intraocular
melanoma
sca le to measure
distance from
optic nerve

Fig. 9.41 CT is less useful than ultrasonography and MRI for intraocular tumours. Ultrasonography and CT are extrem ely helpful
though in the diagnosis of hepatic metastases. Although melanomas enhance with contrast this sign is nonspecific.

PATHOLOGY OF CHOROIDAL MALIGNANT MELANOMAS

Melanoma cells have either spindle or epithelioid morphology.
Malignant melanomas are classified as being of either spindle or
mixed (spindle and epithelioid) cell types, although some tumours
are so necrotic that the cell type cannot be recognized. The
pigment content is variable: some are amelanotic, whereas others
are heavily pigmented. The degree of pigmentation has no
prognostic significance. Bad prognostic factors are the presence of
many epithelioid cells, nuclear polymorphism, monosomy 3 in the
melanoma cells, tumours involving the ciliary body, a diameter
greater than 10 mm, the presence of closed vascular loops, the
presence of a lymphocytic cellular infiltrate and extraocular
extension. In patients over 60 years of age the prognosis is less
favourable. Metastatic disease, which tends to occur initially in the
liver, is the result ofhaematogenous spread and is invariably fatal.

Fig. 9.42 Spindle cells (left) arejusiform with indistinct cell membranes and are arranged in tight bundles. The nuclei vary from slender
to plump; nucleoli may or may not be distinct. Epithelioid cells (right) are larger, polyhedral and more pleomorphic with abundant
cytoplasm. The cell membranes are distinct and extracellular space often separates cells. Nuclei are large with prominent nucleoli. Mitotic
figures are seen more frequently than in spindle cells.
THE UVEAL TRACT

Fig. 9.43 In some tumours spindle cells have a fascicular

arrangement. This has no pathological significance.

t umou r invasion
along scleral
chann el

Fig. 9.44 Uveal melanomas spread usually trans-sclerally along the channels of the vortex veins and ciliary vessels; extension along the
optic nerve is rare .

hyperaemia of
conjunctival vessels lf'--+,.,.,.fc.....,.~

extraocular
tumour ~--~~~~~

dil ated episcleral 1------==-=-- H

vessels L _ _~::::::::,!d....~~-__:::::::::::;;2:::""=---_j

Fig. 9.45 This malignant melanoma of the ciliary body has invaded the iris anteriorly and penetrated the sclera with hyperaemia of the
conjunctival vessels. Scleral spread occurs usually either through the emissary vein or by direct sceral invasion.

TREATMENT OF UVEAL MELANOMAS
Without timely diagnosis and treatment, uveal melanomas can
cause a painful, blind eye and metastasize. About 40-50 per cent
of all patients with uveal melanoma die from metastatic disease
within 15 years of presentation. It is rare for metastatic disease to
be clinically evident before the primary tumour is identified. The
timing of metastatic spread is still unknown but is believed to
occur several years before detection and treatment of the primary
intraocular tumour. Ultrasonography or CT scans of the
abdomen and biochemical liver function tests are indicated when
there is clinical suspicion of hepatic metastases. If screening for
metastatic disease is to be undertaken, such investigations should
be performed every 6 months.
Enucleation for uveal melanoma has largely been superseded
by other treatment that conserves the eye with as much vision as
possible. The choice of therapy depends on several factors. The
most important are the size and location of the tumour; the
CHOROIDAL AND CILIARY MELANOTIC TUMOURS 277
patient's age, general health, occupation and motivation; and the
available skills and equipment. In specialist centres it is usually
possible to preserve the eye if the tumour does not involve the
optic disc or more than one-third of the ciliary body or angle,
does not show transretinal or massive transcleral invasion, and is
not excessively bulky (i.e. more than 16 mm in diameter and
more than 8 mm in thickness). There is a trend for different forms
of treatment to be combined, for example transpupillary
thermotherapy with plaque radiotherapy (i.e. brachytherapy-
radiotherapy given from a short distance, by plaque or seeds), or
local resection with brachytherapy. After apparently successful
conservative therapy, full ophthalmological examination must be
performed by an experienced examiner at least once a year for
the rest of the patient's life so that any local tumour recurrence
can be detected and treated without delay.
Fig. 9.46 In most specialist centres, brachytherapy using a 106 Ru
125
or I plaque is the first choice of treatment. Another method of
directing radiation at the tumour is by means of a highly collimated
beam of heavily charged particles, such as protons, delivered with a
cyclotron. The scope of stereotactic radiotherapy is being
investigated. Transpupillary thermotherapy, which has superseded
photocoagulation, gently raises the tumour temperature to between
45°C and 60°C for about 1 min, by means of a 3-mm diode laser
beam. It is usually used in conjunction with radiotherapy
(sandwich technique), but in some centres it is administered alone
to small tumours located close to the disc or fovea.
Fig. 9.47 After plaque radiotherapy the tumour gradually flattens
over 2- 3 years, usually leaving a residual pigmented mass
surrounded by choroidal atrophy. As long as there is no tumour
regrowth, further treatment is not needed.
78 THE UVEAL TRAcr

Fig. 9.48 In a few centres tumours considered to be unsuitable

for radiotherapy because of their large size or juxtapapillary
location can be treated by local resection, performed either trans-
sclerally or trans-retinally (i.e. endoresection) . With pseudophakic
correction, this dressmaker retained visual acuity of 20/15 and her
occupation 7 years after endoresection of a juxtapapillary choroidal
melanoma in the right eye.

OTHER CHOROIDAL LESIONS

CHOROIDAL METASTASES

These are more common than previously believed, but are often
overlooked if they are asymptomatic or overshadowed by the
patient's terminal illness. They most commonly arise from
primary tumours of the breast in women and of the bronchus in
men. With breast carcinoma there is usually a history of previous
mastectomy or lumpectomy, but metastases from bronchial
carcinoma are more likely to present before the onset of
symptoms from the primary tumour. Patients usually present
with blurring or distortion of vision from macular involvement.
Metastases are usually slightly elevated and amelanotic without
visible tumour vasculature. They are rarely globular and do not
develop a collar-stud shape. There is usually more serous retinal
detachment than with melanomas and ultrasonography shows a
moderate internal acoustic reflectivity. Rapid growth over a
period of weeks is a distinguishing factor from choroidal
melanoma. Choroidal metastases can be observed if
asymptomatic. If treatment is indicated, radiotherapy usually
provides a good response with improvement in vision. Other
methods used include plaque radiotherapy, trans-pupillary
thermotherapy and photodynamic therapy.

Fig. 9.49 Choroidal metastases are amelanotic and tend to grow rapidly so that the retinal pigment epithelium has little time to develop
marked proliferative changes. Such tumours are therefore white or yellow with scattered clumps of residual retinal pigment epithelial cells
giving rise to a leopard-spot pattern. They may be bilateral and in a minority of patients multiple lesions occur in one or both eyes.
 OTHER CHOROIDAL LESIONS 27!

Fig. 9.50 This patient with an intraocular metastasis had widespread secondaries. Biopsy
showed the tumour to be an adenocarcinoma, probably arising from the bronchus.

flatt ish tumour

pa Ie f-b"---:Y::::=-:.. masking by 1-1-,,L.___,;:::.~=::Btt"t::-3d;;;;:;.:H hyper-
metastasis macular RPE fluorescence

Fig. 9.51 This patient with skeletal metastases from carcinoma of the breast presented with bilateral visual loss from pale plaque-like
metastatic lesions at the posterior pole of each eye. She died from carcinomatosis 2 months later.
THE UVEAL TRACT

Fig. 9.52 Histological findings from another patient show plump

pleomorphic cells from a bronchial carcinoma invading the
choroid. Bruch's membrane and the retinal pigment epithelium are
still intact.

UVEAL EFFUSION SYNDROME

thic kened sclera

leopard spot su rface of

ch anges choroi dal effusion
optic nerve

---+-.~,.t-----''<;-----1 low signa l from fl uid

Fig. 9.53 Uveal effusions (see also Ch. 8) may resemble melanoma but are lobulated because of tethering of the choroid to the sclera by
vortex veins (left) . They tend to occur in the horizontal meridian. Acute effusions can be associated with ocular hypotony. Effusions occur
spontaneously as the uveal effusion syndrome in nanophthalmic eyes (axial length < 20 mm), in normal-sized eyes with thickened sclera,
with posterior scleritis and most commonly as a response to hypotony after intraocular surgery. In the absence of hypotony after recent
intraocular surgery the aetiology is thought to be disruption of trans-scleral fluid outflow; if the effusion does not resolve spontaneously
these patients respond to a surgical scleral decompression procedure. Leopard-spot pigmentation can be seen over chronic effusions and
there may be associated serous retinal detachment. Ultrasonography confirms the absence of solid tumour as shown in this patient with
posterior scleritis (right).
Reproduced from Ocular Tumours: Diagnosis and Treatment. Damato: Butterworth Heinemann, 2000.
 OTHER CHOROIDAL LESION

CHOROIDAl HAEMANGIOMA

Choroidal haemangiomas may occur as isolated lesions or as part
of the Sturge- Weber syndrome when they may be associated with
facial and meningeal angiomas, epilepsy, intellectual impairment
and glaucoma from raised episcleral venous pressure (see Ch. 8).
In patients with Sturge-Weber syndrome the haemangioma is
often flat and diffuse involving the whole fundus, giving it a red
'tomato ketchup' appearance. Serous retinal detachment tends to
develop over the tumour, extending inferiorly and to the fovea to
cause the presenting symptoms. These can become extensive and
result in rubeotic glaucoma. Choroidal haemangiomas may bleed
during intraocular surgery causing an expulsive choroidal
haemorrhage.

Fig. 9.54 This child has the typical facial naevus of the Sturge- Weber syndrome. Ocular
involvement is said to be more common when the upper lid is involved by the naevus. Facial
hemihypertrophy is a common feature, as in this patient.
With permission from the patient and his family.

choroidal
haemangioma

Fig. 9.55 These rare tumours usually arise near the posterior
pole of the eye as a slightly elevated lesion. They may be discrete
and up to several disc diameters in size or diffuse. Both types of
haemangioma have indistinct margins and can cause cystic
degeneration and serous detachment of the overlying retina.
Characteristically, they have the same colour as the adjacent
choroid. Haemangiomas usually regress after external-beam or
plaque radiotherapy but this approach is being replaced by
photodynamic therapy.
THE UVEAL TRAG

choroidal haemangioma
with diffuse

Fig. 9.56 On fluorescein angiography, haemangiomas rapidly develop diffuse hyperfluorescence and do not tend to show the same retinal
pigment epithelium changes as melanomas .

lens optic nerve

rF~~"!lt-----c--oo::F,±===-------1 high signal

in tumour
A scan ,iftt,___ _ _JJ high internal
~~±~::::;:2't;s;~::::W~.=.;~~Jt1 reflectivity

Fig. 9.57 On ultrasonography haemangiomas have a

characteristic high internal acoustic reflectivity from the multiple
changes in tissue density throughout their structure which is
diagnostic.

MELANOCYTOMA
A melanocytoma is a densely pigmented benign tumour, usually
situated in the inferior part of the optic disc, but rarely occurring
in other parts of the uvea. It is more commonly found in dark-
skinned people and those with pigmented eyes. Symptoms can
arise as a result of tumour necrosis, which produces optic nerve
well demarcated tumour
in disc substance
central retinal vessels
CONGENITAL HYPERPLASIA OF THE RETINAL PIGMENT EPITHELIUM
Congenital hyperplasia of the retinal pigment epithelium
(CHRPE) is literally a 'spot diagnosis'. These lesions are flat with
a smooth surface that is dark brown or black in colour, and they
often have one or more atrophic spots (lacunae), which can
predominate. The margins are discrete and may have a
hypopigmented border. The lesions may grow gradually over
28
damage in the case of posterior tumours and pigment dispersion
if the tumour is in the ciliary body. These patients require lifelong
monitoring because of the small but definite risk of malignant
transformation to melanoma.
melanocytoma
Fig. 9.58 Melanocytomas may increase in size slowly and
protrude into the vitreous or spread out on to the retina or into the
choroid in which case differentiation from a malignant melanoma
may be exceptionally difficult. Field defects can occur although
visual acuity is not normally affected.
retina
Fig. 9.59 Melanocytomas are well circumscribed tumours
within the optic disc. They are composed of plump, heavily
pigmented melanocytes.
several years and with exceptional rarity may give rise to a nodule,
believed to be an adenoma or low-grade adenocarcinoma, which
is locally invasive. Multiple small, lightly pigmented and spindle-
shaped CHRPE-type lesions may occur in association with
familial adenomatous polyposis or Gardner's syndrome
(dominantly inherited polyposis of the colon) (see Ch. 13).
THE UVEAL TRACT

Fig. 9.60 This photograph shows a typical peripheral area of

retinal pigment epithelial hyperplasia with lacunae. The lesion is
flat and sharply circumscribed with a depigmented margin .

OSSEOUS CHORISTOMA (CHOROIDAL OSTEOMA}

A choristoma is a normal tissue in an abnormal location. Osseous Rarely, such tumours are bilateral or familial. Most patients
choristoma of the choroid is a rare benign tumour that usually retain good vision unless choroidal neovascularization causes
arises adjacent to the optic nerve head. Consisting of bone, it has macular degeneration.
a smooth white surface and is angiographically hyperfluorescent.

Fig. 9.61 This eye shows a juxtapapillary osseous choristoma

adjacent with overlying retinal vascular abnormalities.

orbital shadowing

optic nerve

Fig. 9.62 On ultrasonography, osseous choristomas have a highly

reflective anterior surface and a prominent linear shadow extending
posteriorly into the orbit. Calcification can also be seen on an
orbital CT scan.
 OTHER CHOROIDAL LESIONS

Fig. 9.63 The choroid is replaced by mature bone containing

vascular spaces.
Reproduced with permission from Yanoff and Fine. Ocular Pathology.
Gower Medical Publishing) 1988.

COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM

This malformation usually occurs at the optic disc but may hamartoma. Epiretinal membranes are usually present and the
develop in the peripheral retina. The retinal pigment epithelium retina is stretched into folds, so that the retinal blood vessels are
is irregular, raised and hyperpigmented at the site of the tortuous and vision is reduced.

patchy RPE atrophy

mottled pigmentation
and elevation

Fig. 9.64 These eyes show a combined hamartoma of the retina and retinal pigment epithelium centred on the optic disc with macular
traction and retinal vascular abnormalities.
86 THE UVEAL TRACT
MEDULLOEPITHELIOMA
Medulloepithelioma (previously known as diktyoma) presents in
childhood as a unilateral white, pink or brown, solid or polycystic
ciliary body tumour. These lesions arise from immature
neuroepithelium at the junction of the neurosensory retina and
the nonpigmented epithelium of the pars plana and ciliary body.
white vascu larized tumour
iris
Fig. 9.66 A vascular, pinkish white, ciliary body tumour can be
visualized in these children.
Reproduced from Damato B . Ocular Tumours: Diagnosis and Treatment.
Butterworth H einemann, 2000.
proliferating RPE
RPE ·'.·::... .·: ·.:
opt ic disc
Fig. 9.65 Histological appearance from another patient shows
proliferation of the retinal pigment epithelium through the optic
disc margin into the retina, with proliferating cells and abnormal
vessels.
R eproduced with permission from Yanoff and Fine. Ocular Pathology.
Gower Medical Publishing, 1988.
The tumour must be distinguished from a retinoblastoma. The
tumour is locally invasive and may spread extraocularly if not
treated adequately. Medulloepithelioma can cause secondary
glaucoma, cataract and retinal detachment.
vasculari zed tumour
 OTHER CHOROIDAL LESIONS

Fig. 9.67 Histologically medulloepitheliomas are of two types: nonteratoid and teratoid. The non teratoid tumour (left) has a myxoid or
fibrous stroma in which proliferating epithelial cells form tubules and acini. In the teratoid type (right) the presence of heterologous
elements such as cartilage (as in this case), skeletal muscle or neural tissue can also be found, reflecting the pluripotential nature of the
optic cup. Malignancy depends on the degree of differentiation but metastic deaths are rare .

DISCIFORM MACULAR LESIONS IN THE DIFFERENTIAL DIAGNOSIS OF TUMOURS

subreti nal fibrosis

discrete margin

Fig. 9.68 Macular disciform lesions can resemble melanoma if

they are bulky. Active lesions tend to have subretinal haemorrhage
and exudation, signs that are rare with melanoma. Mature
disciform lesions h ave discrete irregular margins, unlike the smooth
diffuse margins of m elanoma and white subretinal fibrosis . In an
elderly patient a macular mass with vitreous hemorrhage is more
likely to be a disciform lesion than melanoma. The diagnosis
should b e established by waiting for the haemorrhage to clear
spontaneously or by vitrectomy and observing shrinkage of the
lesion. Sequential ultrasonographic scans are likely to show
shrinkage with a disciform lesion and growth with a melanoma.
THE UVEAL TRACT

fresh haemorrh age

sharp margin

Fig. 9.69 Eccentric disciform lesions differ from melanoma in that they are usually associated with haemorrhages and exudates
(left) and because they eventually regress, leaving an irregular scar (right). They are usually temporal and circumferential.
Intraocular
Inflammation
Miles Stanford, David Spalton

Signs of Uveitis
Causes of Uveitis
Anterior Uveitis
Intermediate Uveitis
Posterior Uveitis
White Dot Syndromes
Masquerade Syndromes
290 INTRAOCUlAR INFlAMMATION

The uveal tract consists of the iris, ciliary body and choroid lying
in continuity; inflammation in this tract is known as uveitis.
Uveitis can be classified according to the principal site of
inflammation as anterior uveitis, intermediate uveitis (a subgroup
of which is pars planitis), posterior uveitis or pan uveitis. Because
the uveal tract is continuous, severe inflammation in one part
may be accompanied by signs of overspill inflammation in
another. For example, a severe anterior uveitis (iritis) may be
accompanied by a cellular infiltrate in the ante'rior vitreous (some
ophthalmologists would term this an iridocyclitis). Conversely,
posterior uveitis may be accompanied by signs of inflammation in
the anterior chamber; furthermore, diseases included under the
umbretla of posterior uveitis often have significant retinal signs.
The onset of uveitis may be acute or chronic, defined as
inflammation continuing for more than 3 months. Acute
inflammation produces pain, redness and photophobia and
sometimes blurring of vision, depending on the degree of haze
within the ocular media. Chronic inflammation occurs in a
whiter eye, but clinical appearances may change with time so that
acute symptoms may be followed by chronic uveitis and vice
versa. Granulomatous uveitis is differentiated from the
nongranulomatous type by the appearance of the keratic
precipitates (KPs). In granulomatous uveitis, KPs have a large
pale greasy appearance (mutton fat KP) and the eye is generally
not particularly red. Mutton fat KP used to be taken to indicate
that the uveitis was caused by a systemic granulomatous disease
such as sarcoidosis or tuberculosis but this clinical distinction is
blurred as many of these patients have no detectable underlying
systemic disease. Furthermore, there is often considerable
overlap in the appearance of KPs with granulomatous diseases
such as sarcoidosis sometimes presenting with
nongranulomatous KPs whereas nongranulomatous diseases
such as multiple sclerosis can present with granulomatous KPs.
Whilst uveltls is often thought of as a distinct entity, a
secondary uveitis frequently plays an important role in many
other ocular diseases such as corneal infection, scleritis and
ocular trauma or in surgery, where it is responsible for many
postoperative complications. Uveitis produces visual loss through
cataract or loss of clarity of the ocular media, glaucoma, hypotony
from defective secretion of aqueous humour, retinal or choroidal
destruction, macular oedema or neovascularization.
The eye has a number of particularly unusual immunological
features. The avascularity of the cornea, vitreous and lens and the
physiological blood-aqueous and blood- retina barriers normally
isolate i:he eye from the general immune system. There is no
intraocular lymphatic drainage, so that any ocular immune
response must be mediated through the blood. The immune
privilege enjoyed by the eye is maintained by active
immunosuppression. Resident support cells in the retina such as
astrocytes and Muller cells also have a role in immune
surveillance being able to present antigen, to phagocytose and to
participate in healing and scarring.
Anterior and posterior uveitis appear to be entirely different
diseases. Anterior uveitis is associated with a wide variety of
systemic stimuli (e.g. ankylosing spondylitis, urethritis,
inflammatory bowel disease) in which the initial immune event
appears to be extraocular and then becomes targeted on the eye;
circumstantial evidence suggests a role for autoimmune cross-
reactivity between bowel flora and ocular antigens. Posterior
uveitis is thought to be an example of an organ-specific disease
mediated by T cells reactive to one or more specific antigens
derived from the retina. The discovery that a retinal protein (S
antigen) could induce a retinochoroiditis has led to great
advances in the understanding of the mechanisms of posterior
uveitis in experimental animals although the application to
human disease has so far been disappointing. Several other
retinal proteins such as rhodopsin, opsonin and
interphotoreceptor retinol binding protein have also been found
to be uveitogenic.

SIGNS OF UVEITIS

Inflammation within the eye causes damage to the vascular leucocytes and proteins into the eye. The signs of this process
endothelium of the intraocular vessels with consequent within the eye will depend on the region most affected, the
breakdown of the blood- ocular barriers and exudation of rapidity of onset, its severity and duration.

Fig. 10.1 Ciliary injection is seen here in its classical form as a dusky red
circumlimbal vasodilatation in the area around the cornea where the ciliary and
scleroconjunctival circulations anastomose. Its degree reflects the acuteness and
severity of inflammation in the anterior uveal tract. With very severe inflammation
the whole of the bulbar conjunctiva can be involved and the appearances may be
difficult to distinguish from the diffuse appearance of conjunctival inflammation.
By courtesy of Dr J Krachmer.
Fig. 10.2 Cells in the anterior chamber are a sign of active
inflammation within the eye. The cells are leucocytes that circulate
in the convection currents present within the anterior chamber. In
the slit-lamp beam they have an appearance similar to that of
particles of dust in a sunbeam. They are best seen by a narrow
high-intensity beam directed obliquely across the anterior
chamber.
peripheral iridectomy
Fig. 10.4 Severe vascular damage, usually seen with really acute
inflammation, infection or following surgery will allow even the
largest plasma proteins to exude into the aqueous humour. Such
exudation is manifested by fibrin, which clots in the anterior
chamber to produce the 'plastic' uveitis so typical of HLA-B27-
associated acute anterior uveitis.
Fig. 10.3 A flare within the aqueous humour is the result of a
raised protein concentration from breakdown of the
blood-aqueous barrier together with locally synthesized
immunoglobulin. It defines the slit-lamp beam within the anterior
chamber rather like a car headlight cutting through a foggy night.
Cells usually accompany flare but flare often persists for some time
after the cells have disappeared indicating persistent vascular
damage rather than active inflammation.
Fig. 10.5 Cells within the anterior chamber circulate through the
aqueous humour to agglutinate and become deposited on the
corneal endothelium. They are then known as keratic precipitates
(KPs) and are one of the classical signs of anterior uveitis. KPs are
typically deposited in the inferior quadrant of the cornea, probably
because of gravity and convection currents within the aqueous
humour. They vary in distribution and number and also in size,
colour and shape.
92 INTRAOCULAR INFLAMMATION

pigmented KPs

Fig. 10.6 With resolution of the uveitis with treatment or time the KPs will disappear. Chronic KPs tend to become more pigmented, as
in this patient. These are typical mutton fat KPs; note the whiteness of the eye.

corneal
stroma epithelium
I I
l

- - -
~

I
accumulation of
inflammatory cells
corneal
endothelium
forming KPs

Fig. 10.7 Pathologically KPs consist of a mixture of neutrophils, macrophages and lymphocytes. Neutrophils predominate in newly formed
KPs, whereas macrophages and lymphocytes are deposited later.

pupil distorted by
posterior synechiae

ciliary injection

Fig. 10.8 A massive leucocytic response with an acute anterior uveitis can lead to cells precipitating as a hypopyon. This is typical of
HLA-B27 positive anterior uveitis but is also seen with other causes of severe anterior uveitis such as Beh<;:et's disease. Hypopyon may also
be the presenting sign of retinoblastoma in children, ocular lymphoma and bacterial or fungal endophthalmitis.
 SIGNS OF UVEITIS

Fig. 10.9 Posterior synechiae are adhesions between the pupillary margin and anterior lens surface; they always reflect a previous anterior
uveitis. Pupillary dilatation retracts the iris from contact with the anterior lens capsule and prevents their formation. This is one of the aims
of mydriasis in the treatment of uveitis which will sometimes break weak adhesions to leave tell-tale pigment on the lens . Ring adhesions
will seclude the pupil and prevent aqueous humour flowing anteriorly, causing iris bombe (see Ch. 8).

posterior synechiae

Fig. 10.10 Prolonged and severe inflammation in the anterior chamber produces a cyclitic membrane which can also occlude the pupil.

Koeppe nodule

Iris nodules are granulomas. These are known as Busacca nodules when they are in the stroma. At the pupillary margin they
known as Koeppe nodules; posterior synechiae often form at these positions.
294 INTRAOCULAR INFLAMMATION

Fig. 10.12 Nodules within the peripheral iris stroma can be seen
in this patient with a granulomatous uveitis due to sarcoid.

retroilluminated
vitreous ce lls
and strands

Fig. 10.13 Posterior uveitis produces a cellular vitreous infiltration, analogous to anterior chamber infiltration, but because of the
viscosity and structure of the vitreous gel the cells tend to circulate less and persist for longer. Vitreous cells are sometimes distributed more
locally, for instance over a focus of chorioretinitis or over the ciliary body. Cells may be distributed as a mass of single cells or accumulate
as larger clusters known as 'snowballs'; they can also be seen as retrohyaloid precipitates on a detached posterior vitreous face. Persistent
vitreous inflammation leads to collapse and vitreous detachment with a hazy gel filled with debris.
 ANTERIOR UVEITIS 295

Fig. 10.14 Macular oedema can be seen with posterior uveitis of any type or severity; it is the most common cause of visual loss,
although mild degrees can be compatible with normal visual acuity. Depending on the duration and severity of inflammation, the oedema
resolves with the uveitis leaving a normal macula or progresses to permanent retinal damage . Macular oedema is often difficult to visualize
ophthalmoscopically unless the macula is viewed stereoscopically with a fundus lens (see Ch. 1). Fluorescein angiography can be very
useful in its assessment. In mild cases leakage will be seen from the parafoveal retinal capillaries; in more established cases there is pooling
of fluorescein within the intraretinal cystoid spaces, giving a petalloid appearance to the angiogram. This patient with mild posterior uveitis
had an acuity of 20/60, biomicroscopy showed macular thickening and fluorescein angiography shows marked macular oedema. Optical
coherence tomography (OCT) clearly shows the intraretinal cystic spaces and macular thickening.

CAUSES OF UVEITIS

Anatomically uveltls can be classified into anterior uveltls,
intermediate uveitis (a subgroup of which is pars planitis),
posterior uveitis or panuveitis, although many patients often defy
these strict anatomical divisions. For convenience of diagnosis,
treatment and prognosis it is necessary to know whether uveitis
has a systemic association, is due to an infectious disease or is
idiopathic, in which case it can be subdivided further into
syndromes with specific morphological characteristics. On this
basis some type of diagnostic label can be given to about 70 per
cent of cases. Other conditions such as neoplasia or infection can
masquerade as uveitis.

ANTERIOR UVEITIS

ACUTE ANTERIOR UVEITIS

Acute anterior uveitis (AAU) is the most common type of uveitis
with an incidence of about 15 per 100 000 population per year.
About 50 per cent of patients are HLA-B27 positive compared
with about 8 per cent of the normal population. However, other
factors are important in the pathogenesis, as 25 per cent of
patients with ankylosing spondylitis (more than 90 per cent of
whom are HLA-B27 positive) will suffer an attack of anterior
uveitis during their lifetime compared with only 1 per cent of a
normal population with HLA-B27. Being HLA-B27 positive
correlates with uniocular involvement, increased severity and
joint disease, especially in men but otherwise there are no special
features that distinguish HLA-B27-positive from HLA-B27-
negative patients. Common systemic associations of AAU are
ankylosing spondylitis, psoriatic arthropathy and Reiter's
syndrome, all also linked to HLA-B27. There are many other
associations of AAU but these are uncommon and, in the absence
of any systemic signs or symptoms, it is reasonable to restrict the
investigation of a new patient to a blood count and chest
radiography. More extensive investigations should be reserved for
patients with symptoms of systemic disease or an atypical course.
6 INTRAOCULAR INFLAMMATION

Ankylosing spondylitis

About 50 per cent of Caucasian patients who are HLA-B27
positive will have some signs of ankylosing spondylitis. Young
adult males are predominantly affected with a male: female ratio
of 3 : 1. Attacks of anterior uveitis occur acutely, usually in one
eye and are not related to exacerbations of joint disease, its
severity or any other known predisposing factor. The attacks
usually subside over 4- 6 weeks with treatment and with prompt
treatment do not tend to cause residual ocular damage. Most
patients can expect several attacks of acute anterior uveitis in
either eye before the disease burns out in later life but the degree
to which any one patient is affected is extremely variable. There
is evidence that immune cross-reactivity to bowel flora may have
a pathogenetic role.

sacroi liac joints

sclerosis and
loss of joint space
osteophyte

Fig. 10.15 About 50 per cent of HLA-B27 -positive patients will have evidence of ankylosing spondylitis which is seen in its earliest form
in the sacroiliac joints. There is sclerosis of the periarticular bone with narrowing and irregularity of the joint space, progressing eventually
to ankylosis. Similar changes are seen in the spine.

Reiter's syndrome

This syndrome is a triad of arthritis, urethritis or dysentery, and

acute anterior uveitis. Typically a seronegative (i.e. rheumatoid
factor negative) arthritis affecting large peripheral joints such as
the knees and the sacroiliac joints follows a few weeks after
bacterial dysentery or a nonspecific urethritis. Conjunctivitis and
uveitis occur in 30- 50 per cent of patients. Other systemic
features are plantar fasciitis and keratoderma blennorhagica on
the penis, palms or soles of the feet. Aortic incompetence is a rare
late complication. Males are usually affected; HLA-B27 is
virtually always present and there is evidence that the disease is
related to chlamydia! genital infection if it follows a nonspecific
urethritis. Partial manifestations of the syndrome are common.
In most patients the uveitis recovers over a few weeks but the
arthritis can progress to chronic joint destruction.
Fig. 10.16 This patient has the
typical kyphoscoliotic posture of
ankylosing spondylitis. He has had a
total hip replacement for ankylosis
of the joint. Note the swelling of the
right knee and the deformity of the
feet.

Fig. 10.17 Typical

keratoderma blennorhagica
of the penis.
 ANTERIOR UVEITIS 291

Herpes zoster ophthalmicus

Keratitis (see Ch. 4) and anterior uveitis are common features of

herpes zoster ophthalmicus and may occur independently of
each other. It is said that keratitis and uveitis are particularly
frequent if the vesicles appear along the side of the nose, the
cutaneous distribution of the nasociliary nerve that also
innervates the iris and pupil but this is not invariably so.
The uveitis is frequently subacute in onset and is often
associated with keratitis. It may persist for many months. Sector
atrophy of the iris is commonly seen and is due to an occlusive
vasculitis of the iris vessels; retroillumination of the iris shows
sectorial translucency to advantage. Corneal anaesthesia is
commonly present and persists. Ocular nerve palsies and optic
neuritis are occasionally seen and post-herpetic neuralgia can be
disabling in a minority of patients. Oral antiviral agents should be
given in the acute vesicular cutaneous stage of the disease. The
rash heals more quickly with less post-herpetic neuralgia and a
lower incidence of ocular involvement. The severity of the
cutaneous disease does not necessarily correlate with the degree
of severity of ocular involvement. Herpes zoster in young patients
may indicate an underlying systemic immunosuppressive illness
such as human immunodeficiency virus (HIV) infection or
malignancy.

Fig. 10.18 Herpes zoster ophthalmicus with involvement of the

nasociliary nerve along the lateral border of the nose. Cutaneous
lesions may vary in severity from confluent vesicles to the
occasional punctate lesion.

CHRONIC ANTERIOR UVEITIS

Fig. 10.19 Sectorial iris atrophy following herpes zoster uveitis.
Retroillumination of the iris would show loss of iris pigment
epithelium.
Fig. 10.20 This little girl aged
4 years with pauciarticular
disease has a swollen right knee
on which she cannot weight
bear.
By courtesy of Dr B Ansell.
Juvenile idiopathic arthritis
Juvenile idiopathic arthritis can be divided into three main
subtypes according to the presenting pattern of joint disease.
These are the systemic, polyarticular and pauciarticular types.
Ocular involvement is seen most commonly in the latter group,
particularly in girls, and especially if antinuclear antibodies are
present. HLA-DR5 carries an increased risk of ocular
involvement. Occasionally the uveitis may precede joint
symptoms by up to 2 years. Conversely development of uveitis
after 5 years of joint disease is unusual. Typically the ocular
disease is bilateral and the eye is completely white and painless.
Accordingly there is a need to screen such children on a regular
basis, particularly those at high risk. Visual loss occurs from band
keratopathy, glaucoma or cataract. Many patients can be treated
by topical or local steroid orbital injections; methotrexate is
useful to control both the arthritis and eye disease without the
problems of growth retardation from systemic steroids. Cataract
surgery is frequently required; IOL implantation remains highly
controversial in these children and at present is probably best
avoided. Secondary glaucoma is a serious complication that
responds poorly to standard medical treatment; surgical drainage
with antimetabolites has considerably improved the prognosis.
98 INTRAOCULAR INFLAMMATION
Fuchs' heterochromic cyclitis
This is a distinctive entity with many features not seen with other
forms of uveitis. Small diffuse KPs are scattered over the whole
of the corneal endothelium with a fluffy or feathery appearance
of their border in contrast to the well circumscribed and
inferiorly sited KPs seen with other types of uveitis. The eye is
white and posterior synechiae do not form. The iris has a
characteristic moth-eaten appearance and becomes de-
pigmented, showing a bluish tinge in Caucasian patients. This
depigmentation is not as obvious in heavily pigmented eyes
where iris stromal atrophy is the hallmark. Heterochromic
cyclitis is usually unilateral although bilateral cases rarely occur
and are more difficult to diagnose. Glaucoma may develop and is
Fig. 10.22 The right eye of this patient is normal but the left shows stromal atrophy consistent with Fuchs' heterochromic cyclitis. The left
iris has a slightly bluish tinge. Note the peripheral iridectomy from previous glaucoma surgery.
white eye
posterior
synec hiae
Fig. 10.21 Typical features of chronic anterior uveitis in juvenile
idiopathic arthritis. There is a moderately advanced band
keratopathy with posterior synechiae and a dense cataract. There is
no conjunctival injection.
By courtesy of Mr J Kanski.
associated with a fine neovascularization of the iris and angle (see
Ch. 8). Cataracts are common and are hastened by steroid
therapy; the benefit of steroids in this condition is unproven.
Histopathological examination of iris specimens shows stromal
atrophy with loss of pigment, hyalinization of blood vessel walls,
proliferation of vascular endothelial cells and patchy loss of
pigment epithelium. There is an inflammatory cell infiltrate of
eosinophils, mast cells, lymphocytes and plasma cells; Russell
bodies (immunoglobulins) are present. Recent evidence suggests
that the condition is due to persistent localized rubella viral
infection.
 ANTERIOR UVEITIS

Fig. 10.23 In African Caribbean patients, heterochromia is not seen and iris stromal atrophy is the hallmark. Superficial nodules can be
seen on the stromal surface in some patients.

Fig. 10.24 This photograph shows the typical KPs of Fuch's heterochromic cyclitis. These cover the whole of the endothelial surface and
have 'spidery' margins. A stringy cellular infiltrate can often be seen in the vitreous.
By courtesy of Mr K Barton.
INTRAOCULAR INFLAMMATION

INTERMEDIATE UVEITIS

This usually affects young adults. It is usually bilateral and starts
insidiously. Patients have white eyes and present with floaters
from vitreous debris or blurred vision of gradual onset from
macular oedema. Most cases have no apparent aetiology, but
there is a well recognized association with multiple sclerosis and
similar findings may occasionally be seen in patients with
sarcoidosis. Anterior segment inflammation is minimal. A cellular
vitreous infiltrate is always present in the anterior vitreous gel,
together with snowballs (accumulations of cells), which are
usually seen inferiorly in the peripheral vitreous gel. A low-grade
peripheral periphlebitis is sometimes present. A 'snowbank' is a
massive infiltrate that is sometimes seen inferiorly over the
inferior pars plana and peripheral retina by scleral indentation;
these patients are said to have pars planitis. The snowbank is
composed of collagen, fibroblasts and astrocytes with an
inflammatory cell infiltrate. It is sometimes associated with
fibroglial membranes and neovascularization. Macular oedema
and mild optic disc swelling are common. Neovascularization of
the optic disc or peripheral retina may occur in some eyes. Most
patients have a good visual prognosis with the disease burning
out over a number of years. The most common cause of visual
loss is macular oedema and occasionally vitreous haemorrhage or
retinal detachment (from an associated posterior vitreous
detachment). In some patients intermediate uveitis is associated
with multiple sclerosis which may either precede or succeed the
diagnosis of ocular inflammation.

pars plana
snowbank

Fig. 10.25 A mild snowbank can be seen over the scleral indent.
By courtsey of Dr R J Josephberg.

Fig. 10.26 This 42-year-old man presented with uniocular symptoms but had bilateral signs. The optic disc is normal but there is a trace
of macular oedema with wrinkling of the internal limiting membrane causing blurring of vision. There was a low-grade vitreous cellular
infiltrate, 'snowballs' within the gel inferiorly and periphlebitis of the equatorial retinal veins. The patient was systemically well and all
investigations were normal.
 POSTERIOR UVEITIS

uveitis is less common than anterior uveitis but has a
serious visual prognosis. In all but the mildest cases, orbital
systemic steroids or immunosuppressive drugs are required to
the intraocular inflammation. A diagnostic label can be
to about 70 per cent of patients with posterior uveitis; the
remaining patients have an entirely idiopathic and nonspecific
intraocular inflammation. It is extremely important to recognize
those cases with an infectious or neoplastic cause as specific
therapy may be required.

YSTEMIC DISEASES ASSOCIATED WITH POSTERIOR UVEITIS

ultiple sclerosis

patients with optic neuritis have a subclinical low-grade neurological symptoms many years after the onset of their eye
periphlebitis (Rucker's lines) that resolves spon- problems. Patients with multiple sclerosis may also develop
. The association between intermediate uveitis and granulomatous panuveitis.
sclerosis is well recognized; some patients develop

staining of vein
indicating low-
:;\'==7~1-1 grade periphlebitis

Fig. 10.27 Low-grade subclinical periphlebitis is a common finding in patients presenting with acute optic neuritis.
 LAMMATJON
Sarcoidosis
Sarcoidosis is responsible for about 5 per cent of all cases of
anterior uveitis and is also a common cause of posterior uveitis:
It is a multisystem disorder and ocular involvement of some type
(which may be the presenting feature) is seen in about 25 per
cent of all patients with systemic disease. About 75 per cent of
patients presenting with ocular sarcoidosis will have positive
chest radiographic findings: bilateral hilar lymphadenopathy in
the acute form and pulmonary interstitial fibrosis in the chronic
stage. Although chest radiographic changes provide good
circumstantial evidence of sarcoidosis the diagnosis should be
confirmed histologically where possible by demonstrating
noncaseating granulomas in biopsy tissue. The serum level of
angiotensin-converting enzyme is frequently raised in patients
Fig. 10.29 This 28-year-old woman presented with acute AAU, bilateral hilar
lymphadenopathy and erythema nodosum on her legs.
with systemic sarcoidosis and, although not specific to this
disease, this is a useful diagnostic pointer in patients presenting
with uveitis. It can also act as a marker of disease activity and
response to treatment. The Kviem test is now obsolete.
Anterior uveitis, panuveitis and posterior uveitis with retinal
vasculitis are the most common features of ocular sarcoidosis.
The anterior uveitis may be acute or chronic and either
granulomatous or nongranulomatous. Patients with acute
sarcoidosis and bilateral hilar lymphadenopathy with erythema
nodosum tend to present with acute ocular inflammation,
whereas those with more chronic systemic disease normally have
less acute ocular signs. Patients should be examined for evidence
of granulomas in other common sites such as the lacrimal glands,
eyelids or conjunctiva. Biopsy in these areas is easy to perform
and confirms the diagnosis.
enlarged hilar glands
pulmonary infiltrates
Fig. 10.28 Positive findings of sarcoidosis are found on chest
radiography in about 75 per cent of patients, especially in those
with recent onset of the disease. These patients may have erythema
nodosum. Computed tomography shows the pulmonary changes in
better detail. Bronchoscopy, bronchial lavage and biopsy can be
useful to confirm the diagnosis. Hilar lymphadenopathy usually
resolves spontaneously but systemic steroid therapy may be
indicated in the presence of pulmonary interstitial fibrosis .
 lacrimal gland uptake hilar glands

parotid
upt ake

Fig. 10.30 Radioactive gallium is taken up by macrophages in granulomas (not only with sarcoidosis) and can be used to demonstrate
the extent of systemic involvement with sarcoidosis. This patient shows uptake in the lacrimal glands, nasopharynx and chest.

------
- ~- =------- -

sa rcoid nodules

Fig. 10.31 Sarcoid granulomas in this patient are seen along the lid margin and on the tarsal conjunctiva. ' Blind' biopsy of normal
appearing conjunctiva with multiple sections will sometimes demonstrate noncaseating granulomas.

Fig. 10.32 Lacrimal gland infiltration is common. The gland

must be biopsied transcutaneously to avoid damaging the
conjunctival ductules and exacerbating the risk of a dry eye.
Sarcoidosis is particularly common in African Caribbean patients.
INTRAOCULAR INFLAMMATION

,------------.=-- - - - = - o - - - - - - - - - - - , inflammatory cell

infiltrate

Fig. 10.33 Biopsy of the lacrimal gland shows the typical appearances with a large noncaseating granuloma containing multinucleated
giant cells.

Fig. 10.34 Retinal vasculitis and posterior uveitis can occur in the absence of anterior uveitis; localised areas of focal periphlebitis in the
small peripheral retinal veins are almost pathognomic of sarcoidosis. Typically a creamy white infiltrate 'candle wax' is seen around the
equatorial retinal veins.
 POSTERIOR UVEITIS 30

disc leakage
focal periphlebitis
on angiography
veins appear normal
on ophthalmoscopy

Fig. 10.35 More subtle changes may be observed on fluorescein angiography. This 45-year-old woman presented with a low-grade
posterior uveitis. Focal periphlebitis can be seen on the angiogram, suggesting that the patient has sarcoid.

leaking
neovascular tissue

peripheral
closure

Fig. 10.36 Major venous occlusions, such as central retinal vein occlusion are rare but severe periphlebitis can lead to vascular occlusion
and peripheral vascular closure, which may be followed by neovascularization at the border of perfused and nonperfused retina .
Neovascularization may also occur at the optic disc. It is amenable to photocoagulation of the areas of capillary closure provided that
intraocular inflammation has been adequately suppressed before treatment.

periphlebitis

massive
granulomatous
_.,.,._~..,..~~-+---1 infiltration
of optic disc

Fig. 10.37 Optic disc swelling may result from local oedema
with posterior uveitis, local infiltration with sarcoid granulomata,
optic nerve compression by a granuloma at the orbital apex or,
occasionally, from raised intracranial pressure with neurosarcoid.
Chronic optic nerve infiltration can cause optic atrophy in the
absence of disc swelling. This patient with neurosarcoid has a
massive granuloma of the disc.
INTRAOCULAR INFLAMMATION
fresh ere a my
subretina l infiltrate
Fig. 10.38 Focal atrophic retinal pigment epithelial (RPE) changes are often seen in the inferior fundus, particularly in middle-aged and
elderly women with long-standing disease. They are due to granulomatous change in the RPE or choroid. Initially the lesions have a fluffy
creamy appearance that resolves to leave atrophic RPE changes.
Beh~et's disease
Behvet's disease was originally described in males of Eastern
Mediterranean origin but is increasingly recognized, often in less
dramatic forms, in females and other racial groups. The diagnosis
is made clinically and is based on the triad of uveitis, oral and
genital ulceration. The clinical signs are divided into major
criteria of mouth or genital ulceration, uveitis and skin lesions
(erythema nodosum, thrombophlebitis, folliculitis) and minor
criteria such as arthritis, gastrointestinal ulceration, venous
occlusions and neurological signs. The aetiology of Behvet's
disease is unknown. Ocular involvement is particularly related to
the presence of the HLA-B51 antigen which has a prevalence of
about 60 per cent in most populations studied.
pale granuloma ~""""'===~~~ pigmented
trabecular
meshwork
Fig. 10.39 Granulomas may be seen on the trabecular meshwork
in ocular sarcoid. They can lead to secondary glaucoma from
peripheral anterior synechiae.
Behvet's disease carries a poorer visual prognosis than almost
any other form of posterior uveitis. Many patients will respond to
systemic steroids but cytotoxic treatment is indicated in patients
with severe ocular disease. Cyclosporin A is very useful in the
management of these patients although the drug itself carries a
risk of systemic toxicity and withdrawal of treatment may cause
a florid relapse of uveitis. Mycophenolate mofetil is less toxic and
an increasing range of newer immunologically based treatments
such as interferon and anti-tumour necrosis factor a drugs are
becoming available; these agents are likely to have an increasing
impact in the management of severe disease.
 POSTERIOR UVEITIS 307

Fig. 10.40 Mouth ulcers are painful and episodic and cannot be Fig. 10.41 Genital ulcers are not seen as frequently as mouth
distinguished clinically or pathologically from aphthous ulceration. ulcers. This patient has active ulceration but white scars can be
Their presence often predates ocular symptoms sometimes by seen at sites of previous ulceration.
many years.

Fig. 10.42 Recurrent hypopyon is a widely recognized feature of

severe Beh<;et's disease . There is a brisk cellular reaction in the
anterior chamber often with a surprising lack of conjunctival
injection. Patients with disease that is confined to the anterior
segment alone have a better prognosis.

inferior temporal branch

retinal vein occlusion

Fig. 10.43 The posterior uveitis of Beh<;et's disease may be asymmetrical or even
unilateral. There is usually diffuse vascular leakage throughout the fundus; focal
periphlebitis (as seen in sarcoidosis) is not a feature of Beh<;et's disease. This patient has an
inferior branch retinal vein occlusion. Venous occlusion in the presence of posterior uveitis
should always suggest the diagnosis of Beh<;et's disease .

Fig. 10.44 This 33-year-old man presented with a history of oral ulcers
and visual loss in his left eye with a mild posterior uveitis. The fluorescein
angiogram shows a macular branch vein occlusion occurring along the
vessel in the absence of an AV crossing indicating that the occlusion is
vasculitic.
INTRAOCULAR INFLAMMATION

fresh retinal infiltrate

Fig. 10.45 White infiltrates of the inner retina sometimes associated with intraretinal haemorrhage can occur during the active phases of
Behyet's disease. Pathologically these are areas of neutrophils infiltrating the retina . In this patient the infiltrates resolved over a period of
2-3 weeks with treatment leaving the retinal pigment epithelium and retinal vasculature looking undisturbed.

Fig. 10.46 In the terminal phase there is optic atrophy secondary to destruction of the retina and its vasculature. The retinal arteries look
like white threads from nonperfusion and gliosis. Although there is some disturbance at the macula, pigmentary changes are comparatively
sparse for the severity of the disease.
By courtesy of Dr E M Graham.

Fig. 10.47 Major venous occlusions are seen elsewhere in Beh~et's disease . This
patient has had an inferior vena cava thrombosis with a caput medusa due to
venous bypass through the cutaneous veins of the abdominal wall.
 POSTERIOR UVEITIS

INFECTIVE CAUSES OF POSTERIOR UVEITIS

These are an extremely important group of conditions to
recognize as specific therapy may be required . HIV must always
be considered as an additional underlying factor, particularly if
the patient has sexual or intravenous drug use risk factors, comes
from an endemic area or has atypical or florid disease.
Toxoplasmosis
Ocular toxoplasmosis is one of the commonest causes of
posterior uveitis. Congenital ocular toxoplasmosis is acquired by
transplacental infection of the fetus from a nonimmunized
infected mother. The disease is extremelyrcommon in some parts ·
of the world such as South America and West Africa and it seems
that ocular involvement from acquired systemic disease in a
nonimmunized patient is much more common than has been
previously realized. The animal reservoir is in the cat and the
organism has a predilection for neurological tissue. The parasite
can persist encysted in the retina for many years. Retinal damage
appears to be due to a combination of proliferating Toxoplasma
organisms released from their cysts and directly invading the
retinal cells, an inflammatory response, and possibly a secondary
autoimmune reaction. IgM antibodies indicate recent infection;
IgG antibodies indicate only previous infection and their level
does not increase with relapsing retinal disease .
Toxoplasmosis is one of the few causes of uveitis that can be
diagnosed by the fundal appearance; it does not cause anterior
uveitis in the absence of fundal lesions which are pigmented,
circumscribed scars usually in the posterior poles of one or both
eyes. Visual acuity is lost if the macula or its axons are involved,
but visual field defects can be caused by lesions elsewhere. The
fundal lesions remain quiescent but have a tendency to reactivate
in adults aged between 20 and 40 years producing a fluffy, white,
chorioretinal lesion adjacent to previous chorioretinal scarring
with posterior uveitis. If the lesion is small vitreous infiltration
may be localized to this area. The activity of the lesions subsides
over 3-4 months leaving ·further chorioretinal scarring. Many
patients with mild reactivation of toxoplasmosis will settle
without any treatment but if the macula or optic disc is
threatened treatment with sulfonamides and pyrimethamine or
clindamycin to destroy the organism, together with systemic
steroids to suppress the inflammatory response, is usually given.
No randomized controlled trial of such treatment has, however,
shown benefit.

copper beaten sku ll intracran ial

from hydrocephalus calcification

Fig. 10.48 Seroconversion during pregnancy carries a high risk of fetal damage, particularly in the first trimester, but it is exceptional for
visual acuity to be lost in both eyes. Severe intracranial infection in a fetus can produce intracranial calcification, hydrocephalus, intellectual
impairment and epilepsy.

Fig. 10.49 This is a typical quiescent Toxoplasma scar in the posterior pole. It is sharply
circumscribed with retinal hyperpigmentation and pigment epithelial atrophy. Note the
associated retinal nerve fibre defect. - .
INTRAOCULAR INFLAMMATION

old
pigmentation

fresh infiltrate

Fig. 10.50 The fellow eye of the same patient as in Fig. 10.49
shows reactivation next to an area of previous scarring. A few
weeks later the area of retinal necrosis with inflammatory infiltrate
has become more discrete and the vitreous is clearing, leaving
further retinal destruction and pigment atrophy. Note the
associated posterior vitreous detachment.

juxtapapillary
'-----~'-'---"" chorioretinitis

swollen disc

Fig 10.51 A particular feature of active toxoplasmic

chorioretinitis is an arteritis of neighbouring vessels.

cloudy swel ling from

branch artery occlusion

Fig. 10.52 Acquired toxoplasmosis is rare . A fresh circumscribed

lesion is seen in the fundus with no evidence of previous scarring
or pigmentation. The patient had a systemic febrile illness with
lymphadenopathy. lgM anJibodies to Toxoplasma were found in the
blood.
 POSTERIOR UVEITIS

Fig. 10.53 The pathology of toxoplasmosis is primarily retinal necrosis with secondary choroidal changes. After infection the organism
remains encysted and intracellular in the retina as inactive bradyzoites (left) for many years. At some stage, for unknown reasons, the cyst
ruptures to release the active tachyzoites (right). These proliferate to cause a necrotic retinitis before encysting again.
Left figure by courtesy of Mr C Pavesio.

Toxocariasis

The nematode Toxocara canis has its reservoir in dogs, especially
young puppies; the ova persist for long periods in contaminated
soil. Visceral larva migrans is the systemic form of acute
toxocariasis. This occurs in older children and is associated with
pulmonary infiltrates and transient eosinophilia; ocular
involvement is comparatively uncommon. Ocular toxocariasis is
typically seen in 2-4 year olds particularly if they have a tendency
to eat dirt or have contact with puppies. The larvae migrate
through the gut wall and can disseminate to the eye where they
incite a granulomatous reaction. Toxocariasis occurs in two
forms: a massive exudative white lesion containing the nematode
in the posterior pole (sometimes presenting in a child as a poorly
sighted eye with leucocoria) and a peripheral form with smaller
white lesions in the equatorial retina with bands of retinal
traction. There may be marked posterior uveitis. The disease is
usually uniocular. Affected eyes are white and inflammatory signs
are confined to the vitreous gel.
A positive serum enzyme-linked immunossorbent assay
(ELISA) confirms previous infection by Toxocara; this may be
negative with ocular disease and it may be necessary to repeat the
test on aqueous or vitreous to confirm the diagnosis. In young
children it is extremely important to distinguish toxocariasis
from its main differential diagnosis, retinoblastoma. Apart from
steroids to suppress the inflammatory response no other drug
treatment is of proven benefit. It is possible, however, in some
cases to remove the granuloma by vitreoretinal surgery and to
clear the vitreous gel if there is chronic endophthalmitis.

Fig. 10.54 This is the fundus appearance of a 3-year-old child with a 6-month history of
unilateral nonprogressive visual loss. A large white central granuloma has caused retinal traction.
Visual acuity was counting fingers; the ELISA test was strongly positive and the family owned a
puppy.
INTRAOCULAR INFLAMMATION
posterior pol e
granuloma
Fig. 10.55 Histological examination demonstrates a granuloma at the posterior pole of an infected eye. Serial sections and higher power
demonstrate the encysted nematode.
Syphilis
Syphilis during pregnancy infects the fetus and produces a
retinopathy. Active lesions are rarely seen in the neonate but are
said to be focal, yellowish, spotty retinal pigment epithelial
changes associated with vasculitis. This resolves to leave
pigmentary scarring with areas of focal pigmentation and atrophy
in the peripheral retina, the so-called 'pepper and salt' fundus
which can sometimes be confused with retinitis pigmentosa.
Following congenital syphilis, interstitial keratitis (see Ch. 6) may
appear between the ages of 5 and 25 years. Patients may have
other stigmata of infection such as nasal and dental deformities
or nerve deafness. Progressive neurological deficit is, however,
relatively uncommon.
Secondary syphilis, although rare, is becoming more common
again and should be considered in any atypical intraocular
inflammation, whether anterior or posterior, because of the
serious consequences of missing the diagnosis. The absorption
fluorescent treponema! antibody test (FTA Abs) is highly
~ (] ""'
--.:...-::: 0"
[>
nematode of
Toxocara canis
f ibrous tissue
, ·' ~ ~ "' and a few
""' inflammat ory
oo ; nq cells
specific, and active infection can be distinguished from latent or
treated infection by demonstrating IgM or IgG antibodies. The
cerebrospinal fluid should be examined in all patients with ocular
syphilis. Secondary syphilis is usually associated with a typical
maculopapular rash on the limbs, trunk, hands and feet. Acute
iritis may be present with iris papules known as roseola . More
commonly chorioretinitis may be present with a mild posterior
uveitis with focal, yellowish, subretinal infiltrates. The optic disc
may be swollen and there may be serous retinal detachment.
Patients who are HIV positive tend to show much more florid
signs. Syphilitic retinopathy, if untreated, may resolve to leave a
pigmentary retinopathy with arterial narrowing, optic disc pallor,
and retinal pigment epithelial atrophy and scattered intraretinal
pigmentation from RPE proliferation. Syphilitic chorio-
retinopathy can usually be distinguished from true retinitis
pigmentosa as visual fields and visual function are much better
than would be expected with a retinal dystrophy.
Fig. 10.56 These photographs show the typical maculopapular
rash on the hands from secondary syphilis. Spirochaetes can be
found in the lesions by examining their exudate with dark field
illumination.
 Fig. 10.57 Patients with secondary syphilis usually have a mild posterior
uveitis. Widespread yellowish subretinal infiltrates are a common feature and
can suggest the diagnosis. This patient was also HIV and hepatitis B positive.

intraretinal pigment

Fig. 10.58 This patient was known to have had congenital syphilis. The optic disc is pale, retinal vessels are attenuated and there is
IWI(ieSlDre:ad chorioretinal atrophy. The equatorial retina shows large clumps of intraretinal pigmentation. Patients often have good visual
despite their retinopathy. Visual loss is usually due to keratitis and subsequent cataract formation .

lar tuberculosis

Ocular tuberculosis is rare but should always be considered in
patients with atypical anterior uveitis, retinal vasculitis or
choroidal infiltrates, particularly in the presence of HIV. Patients
usually have a florid positive tuberculin (Mantoux Heat Test).
Patients require chest radiographs and culture of sputum and
urine for tuberculi bacilli. Systemic evidence of active
tuberculosis can be difficult to substantiate. Circumstantial
proof of the diagnosis is often demonstrated by rapid
improvement in the ocular signs with a short course of
antituberculous chemotherapy. Systemic steroids may be
required for control of the ocular inflammation but if there is a
possibility of tuberculosis appropriate chemotherapy must be
given to prevent disseminated systemic disease . Eales' disease
(retinal vasculitis, peripheral vascular closure and n eo-
vascularization with a strange propensity to affect the left eye)
is particularly common in the Indian subcontinent and is
thought to be associated with a hypersensitivity response to
tuberculin.
 corneal oedema clear cornea
reso lut ion of KP
iris nodu les and iris nodules

Fig. 10.59 This Pakistani woman had a chronic anterior uveitis with marked nodular involvement of the iris, unresponsive to topical
steroid treatment. Chest radiography showed old tuberculous changes and the patient had a strongly positive Mantoux reaction although
sputum culture was negative. The iris appearance improved dramatically after 2 weeks of antituberculous chemotherapy.

Fig. 10.60 This patient had miliary tuberculosis; a single choroidal tubercule can be seen as a creamy, diffuse, subretinal swelling.
Nonspecific pigment epithelial scarring remains after appropriate chemotherapy. Choroidal tubercles are frequently bilateral and multifocal.
---------·-········-------------
POSTERIOR UVEITIS

severe periphl ebitis

Fig. 10.61 Florid retinal vasculitis can be associated with tuberculosis, especially in Asiatic patients. Posterior uveitis is relatively mild but
retinal vasculitis is marked and there is vascular closure and haemorrhage which frequently progresses to neovascularization. The
fluorescein angiogram showed peripheral closure with early new vessels and patchy leakage.

Acute retinal necrosis

Patients present with vitreous cellular infiltrate and characteristic
patchy, fluffy white areas in the peripheral fundus that become
confluent areas of whitish retinal necrosis, associated with
occlusive arteritis and granulomatous anterior uveitis that
progress to increasing retinal destruction and detachment if
untreated. Both eyes are ultimately involved in 20-80 per cent of
patients. The disease is caused by herpes simplex or zoster. The
retinal changes are similar with each virus, but patients with
simplex infection tend to be younger (less than 40 years) in
comparison to those with zoster (above 50 years). Acute retinal
necrosis may sometimes follow a recent herpes simplex
cutaneous eruption or encephalitis. It can occur in either entirely
healthy or immunosuppressed patients. It is important to identify
the causative virus by polymerase chain reaction (PCR) on a
vitreous biopsy to target specific antiviral therapy. Treatment with
intravenous antivirals for 10 days followed by oral therapy for 3
months usually halts the disease and prevents relapse or
progression into the other eye. Patients with HIV may relapse
with cessation of treatment. Following successful treatment,
retinal detachment with giant tears occurring along the
demarcation line between normal and affected retina happens in
up to 75 per cent of patients 4-8 weeks after the onset of retinitis;
prophylactic treatment to prevent this with vitrectomy and endo-
laser remains controversial.

optic disc

Fig. 10.62 Acute retinal necrosis. This otherwise fit 56-year-old man presented with
blurred vision in his left eye of 5 days' duration. The fundal view is very hazy because
of the vitreous infiltrate but patchy white retinal infiltrates can be discerned nasal to
the disc.
 MMATION

Fig. 10.63 Vitreous biopsy was positive for herpes zoster on PCR. After 5 days of intravenous antiviral treatment the retinal appearances
are clearing and the infiltrates can be seen more clearly.

>c<_·.,.--...., optic atrophy

gross vascu lar

r ----+--1 attenuation

Fig. 10.64 Three months later the patient suffered a retinal detachment that
was treated with silicone oil and endo-laser, leaving HM vision . Note the optic
atrophy and marked vascular closure.

retinal arteritis

Fig. 10.65 This patient shows an arteritis coexistent with peripheral acute
necrosis. Optic disc and optic nerve arteritis are common in acute retinal
necrosis and may contribute to the visual loss. The patient had a positive PCR
for herpes zoster.
 POSTERIOR UVEITIS 317

Acquired immune deficiency syndrome (AIDS)

HIV-associated diseases should be considered in any patient with
uveitis with social risk factors, from a high prevalence area or
with unusual or atypical uveitis. Both Kaposi's sarcoma (see Ch.
3) and herpes zoster (see Ch. 4) can affect the anterior segment.
Idiopathic cotton wool spots may be seen in a number of cases as
transient lesions that disappear spontaneously within 6- 8 weeks.
The commonest form of retinal infection is cytomegalovirus
retinitis although this has become less common with the success
of highly active antiretroviral (HAART) therapy. Cyto-
megalovirus retinitis is associated with CD4 counts of less than
50 and is uncommon if the count is over 100. Untreated the
retinopathy progresses slowly. Both eyes become involved and
the lesions relentlessly increase in area with the central part of the
lesion becoming atrophic. The retina is destroyed within 6
months. Retinal detachment is common.
A wide variety of other opportunistic infections occur less
commonly including toxoplasmosis, herpes simplex or zoster
retinitis, cryptococcosis, atypical mycobacteria and Pneumocystis
carinii. Secondary syphilis is well recognized and produces a
more florid uveitis than in otherwise normal individuals.
Intraocular lymphoma must also be considered.
Immune recovery uveitis is seen in patients who have had
cytomegalovirus retinitis that has been treated and become
quiescent on maintenance therapy. As their CD4 count rises to
above 100 with HAART therapy these patients develop a low-
grade intermediate type of uveitis with cystoid macular oedema.

multiple
cotton w ool spots

Fig. 10.66 HIV retinopathy is the most common form of ocular involvement in patients with AIDS and is seen in more than 50 per cent
of patients prior to HAART. Cottonwool spots are seen in the posterior pole; they are asymptomatic and resolve over 4- 6 weeks. They are
thought to be caused by HIV infection of retinal vascular endothelium causing microinfarction.
Fig. 10.67 This 46-year-old man presented with poor vision in his left eye. Examination showed a macular lesion with a peripheral lesion
typical of cytomegalovirus retinitis. There are creamy areas of retinal necrosis and haemorrhage alongside retinal vessels with a minimal
vitreous cellular infiltrate.

optic atrophy

attenuated arteries
atrophic retina

Fig. 10.68 The patient was treated with ganciclovir and the Fig. 10.69 The patient responded to another course of
lesions improved, but relapsed 3 months later when he ganciclovir and continued to take maintenance therapy. At this
discontinued treatment. This led to further retinal destruction and stage the fundi are quiescent with areas of retinal atrophy, pallor of
involvement of the fellow eye . the optic discs and vascular attenuation .
 cells containing
CMV inclusion spa rse inf lammat ory
bodies ce lls

Fig. 10.70 Pathological examination of the same patient shows areas of complete retinal destruction with a sparse inflammatory cellular
infiltrate and the typical 'owl's eye' intracellular inclusions of cytomegalovirus.

Fig. 10.71 Progressive outer retinal necrosis (PORN) is a
multifocal form of herpes zoster retinitis seen in patients with
AIDS with very low CD4 counts. It is usually bilateral with
minimal signs of ocular inflammation. The deep retinal lesions
rapidly become confluent with total visual loss.
By courtesy of Dr P McCluskey.
Fig. 10.72 Choroidal pneumocystis is characterized by multiple
subretinal plaques 1-3 disc diameters in size in the posterior pole.
The lesions slowly enlarge in the absence of inflammation. Vision is
usually good. The ocular lesions are an early sign of life-threatening
systemic infection.
By courtesy of Dr EM Graham.
Subacute sclerosing panencephalitis
This rare condition is due to persistent measles infection in the
brain. It affects children aged 6-14 years and is fatal from
progressive neurological degeneration over 1-2 years. Patients
retinal infiltrate
WHITE DOT SYNDROMES
This is a group of diverse conditions in which the primary
pathology appears to lie in the outer retina, RPE or
choriocapillaris of unknown aetiology. In a subgroup of these
conditions the lesion appears to lie at the level of the RPE- the
'retinal pigment epitheliopathies'-and is characterized by deep,
pale swelling of the pigment epithelium in the acute phase of the
disease, which masks fluorescence in early fluorescein
angiograms, followed by staining in the later stages. The lesions
heal leaving pigmentary changes. Inflammatory signs can be
ACUTE MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY (AMPPE)
This syndrome usually occurs in young or middle-aged adults
and is usually bilateral. There is sometimes a history of preceding
'flu-like illness or respiratory infection. Patients present with
blurred vision of fairly rapid onset over a few days with mild
vitreous infiltration and anterior uveitis. Focal, pale, swollen
areas with a fluffy border about half a disc in diameter are seen
deep to the neuroretina in the posterior pole and are thought to
represent areas of oedematous and swollen RPE cells. These
present with myoclonic jerks and intellectual impairment. The
EEG and cerebrospinal fluid (CSF) changes are diagnostic.
retinal periphlebitis
Fig. 10.73 There is a mild posterior uveitis
retinal infiltrates with retinal infiltrates later progressing to
pigmentary atrophy.
variable. The aetiology is presumed to be either a vasculitic or an
ischaemic lesion of the choriocapillaris with infarction of the
overlying RPE, or, alternatively, an immunological response
directed at the RPE. Acute multifocal placoid pigment
epitheliopathy, Vogt-Koyanagi- Harada's syndrome and sympa-
thetic ophthalmitis all have fundus features in common. Although
milder cases are usually restricted to the eye, systemic vasculitis
can be seen with all types.
produce characteristic appearances on fluorescein angiography.
The lesions are hypofluorescent on early angiography, masking
the background choroidal fluorescence. In later angiograms the
lesions stain with fluorescein .
The lesions of AMPPE all appear and evolve in phase. Over
2-3 weeks the acute phase of the condition resolves with
subretinal pigmentary changes and, usually, a return to near-
normal acuity over the next few months.
 WHITE SPOT SYNDROMES

Fig. 10.74 Acute placoid lesions are seen as

typical creamy white subretinal lesions about one-
quarter to one-half a disc in diameter and
scattered throughout the posterior pole with some
early pigmentary changes. Serous retinal
detachment may be present in the acute stage.

ma sking of choroidal lat e

>0=-'-'..--1 fl uorescence hyperfluorescence

RPE atrophy

mid-phase late phase

L_.::::O~DQ:::::::__ _ j ang iogram L___ ___:::,__--"-~'---__j angiogram

Fig. 10.75 Early and late fluorescein angiograms of the same patient show typical masking of background fluorescence in the early stages
with later leakage and staining of the lesion.

Fig. 10.76 Three months later the acute lesions

healed to leave irregular atrophy and scarring of
the RPE. Vision returned to normal. Fluorescein
angiography demonstrates the extensive
pigmentary disturbance . Relapses are rare.
VOGT-KOYANAGI-HARADA {VKH) SYNDROME
Harada's disease (posterior uveitis and CSF pleocytosis) and the
Vogt-Koyanagi syndrome (posterior uveitis, dysacousia and
vitiligo) appear to be part of the same disease. The aetiology of
the condition is unknown but there is a strong racial influence in
that it is much more common in the Far East and accounts for
6-7 per cent of all cases of uveitis in Japan. Many Western
patients with the disease have some oriental ancestry. An
association with HLA-DR4 and DRw53 has been observed in
Japan and there are noticeable clinical and pathological
similarities to sympathetic ophthalmitis, although the visual
prognosis with VKH syndrome is usually better.
The pathogenesis is unknown but a selective autoimmune
targeting of melanocytes would explain the ocular, neurological
and cutaneous features of the disease. Young or middle-aged
adults are affected in both eyes. There is frequently a short
Fig. 10.77 This 13-year-old Arab girl presented with a 2-week
febrile illness, severe headache and hearing disturbances and then
developed a severe bilateral posterior uveitis. Three months later
she has greying hair and vitiligo on her forehead.
prodromal illness of headache and mild malaise or meningism
before visual loss starts over a few days. This is followed by the
uveitic phase. Both eyes are affected. Posterior uveitis is always
present; there may be granulomatous anterior uveitis which
varies from minimal to severe. Multiple small spots of leakage
through the RPE are seen on angiography with pooling of dye in
the subretinal space and eventually serous retinal detachment
(similar changes can be seen with posterior scleritis). In the acute
stages,- patients may have pleocytosis of the CSF and dysacousia
that tends to resolve fairly rapidly. In the chronic phase over the
next few months there is depigmentation of the choroid.
Dalen-Fuchs' nodules can be seen in the equatorial fundus.
Alopecia, vitiligo and poliosis may follow weeks to months later,
and relapses of anterior uveitis may occur.
Fig. 10.78 A close-up photograph shows poliosis of the girl's
eyelashes and eyebrows.
subretinal
yellowish infiltrate
1\'"'""---!--11--~:].__j folds from
subretinal fluid
Fig. 10.79 In the acute phase, fundus examination shows
exudative retinal detachment with optic disc oedema. Yellowish
mottled lesions can be seen at the level of the RPE.
By courtesy of Dr P McCluskey.
 WHITE SPOT SYNDROMES

subretinal fluid and

bullous retinal
detachment

Fig. 10.80 In this patient there is shallow subretinal fluid and

disc swelling with subtle yellowish RPE changes. Fluorescein
angiography shows multiple areas of pinpoint leakage through the
RPE corresponding to some of these lesions. Pooling of dye in the
subretinal space can be seen in the fellow eye in the late phase.
Similar angiographic changes can be seen with posterior scleritis.
By courtsey of Dr P McCluskey.
INTRAOCULAR INFLAMMATION

hyperpigmentation
in macular area
diffuse disturbance
of retinal pigment
mild optic disc epithelium
swelling Fig. 10.81 As the inflammation resolves with
treatment the subretinal fluid absorbs typically
peripapillary halo
retinal folds and leaving widespread scarring of the RPE throughout
subretinal fluid the posterior pole and a peripapillary halo.

Fig. 10.82 The same patient as

Fig 10.80 shows white bands of
subretinal scarring following
resolution.

SYMPATHETIC OPHTHALMITIS

This is a bilateral granulomatous panuveitis that follows a
perforating injury to one eye (the injured or exciting eye). It
virtually always follows traumatic or surgical perforation,
although cases have been reported after nonperforating injury and
laser or cyclocryotherapy. Rare cases may be associated with
perforating corneal ulcers or malignant melanoma with
extraocular extension. Most cases, however, involve traumatic
perforation of the anterior segment with damage to the iris or
ciliary body. In the American Civil War it is estimated that as many
as 16 per cent of perforating injuries were followed by sympathetic
ophthalmitis. The disease has become much less common with
recognition of the need for prompt microsurgical repair of ocular
perforations and the meticulous removal of prolapsed uveal tissue
from the wound; today the disease is more commonly seen
following multiple surgical, usually vitreoretinal, procedures. The
incidence is thought to be in the order of 0.1 per cent of ocular
traumatic perforations. Sympathetic ophthalmitis occurs from
childhood to old age and there is no sex or racial preponderance;
however, an immunogenetic influence is important as patients
have similar HLA antigens as those with VKH syndrome.
The length of the latent interval between perforation and
inflammation of the noninjured or sympathizing eye is very
variable. Frequently the exciting eye never completely settles
down after the injury but sympathetic ophthalmitis can follow a
completely quiet eye. About 65 per cent of cases present within
2 weeks to 3 months of the original injury and the majority have
occurred within 2 years, although a few cases have been reported
to occur many years later.
The patient presents with an acute granulomatous uveitis of
the sympathizing eye. Early enucleation of the traumatized eye
before the onset of inflammation prevents sympathetic
ophthalmitis but whether or not the exciting eye should be
removed after the development of sympathizing symptoms is
controversial. There is some evidence that enucleation within the
first weeks may be beneficial to the course of the disease but eyes
with visual potential should never be removed. Visual acuity is
lost from cataract, glaucoma, macular oedema and vitreous
opacification. The previously poor visual prognosis has been
considerably improved by treatment with systemic steroids and
cytotoxic drugs and, provided the inflammation is controlled,
these eyes do well with further surgery. The pathogenesis of the
condition is unknown, but it is probably an autoimmune reaction
to one or more retinal antigens.

Fig. 10.83 This 63-year-old man developed sympathetic ophthalmitis 3 years after
a perforating injury and multiple surgical procedures to the left eye and presented
with blurred vision, floaters and panuveitis. Fundus examination shows multiple
focal areas of RPE depigmentation at the site of Dalen- Fuchs' nodules. Fresh lesions
have a fluffy creamy appearance; older lesions are whiter and more demarcated with
RPE atrophy. Fluorescein angiography shows leakage from the optic disc, cystoid
macular oedema, hyperfluorescence from the fresh lesions and window defects in the
atrophic lesions.

Fig. 10.84 Histologically, in sympathetic ophthalmitis lymphocytes (initially

CD4 cells, later CDS cells) infiltrate the uvea. (Top left) Lymphocytic
infiltration with granuloma formation in the choroid. (Top right) Pigment
phagocytosis by epithelioid cells. (Bottom left) Dalen- Fuchs' nodule (i.e. a
granuloma between Bruch's membrane and the RPE).
SERPIGINOUS OR GEOGRAPHICAL CHOROIDITIS
This rare condition usually occurs in middle-aged patients, is
bilateral (although frequently asymmetrical) and the changes in
one eye may precede those in the other by many years. The eyes
are white and there is minimal vitreous infiltration. The
characteristic early lesion is an area of pale RPE atrophy in the
posterior pole in the vicinity of the optic disc which has a
relapsing and remitting course over several years. Relapses are
seen as an area of greyish subretinal swelling contiguous with
Fig. 10.85 This patient shows old serpiginous scarring in the posterior pole of the right eye with a fresh lesion on the temporal periphery.
In the left eye there is a single patch of RPE atrophy.
BIRDSHOT CHORIORETINOPATHY
Birdshot chorioretinopathy is an uncommon cause of posterior
uveitis occurring in young or middle-aged adults; it usually
affects both eyes. The association of birdshot with HLA-A29 is
the strongest HLA association known for any disease. Patients
present with blurred vision and floaters; complaints of disturbed
night or colour vision also occur. Mild posterior uveitis is present
with a quiet anterior chamber. Multiple areas of characteristic
focal subretinal depigmentation of about one-quarter to one-half
a disc in diameter with diffuse margins are seen in the posterior
the edge of a lesion that spreads equatorially in a serpiginous
fashion. In the active state fluorescein angiography shows early
masking followed by late leakage in the same area. The lesion
resolves over several weeks with destruction of the overlying
retina and an increase in the scotoma to reappear elsewhere on
the border of the lesion at a later date. Visual acuity is lost if the
macula is affected. No treatment seems to affect the course of
the disease.
minimal early
RPE changes
pole. The lesions are never pigmented. On fluorescein
angiography some lesions show early hypofluorescence and late
hyperfluorescence but many lesions do not cause fluorescence
changes; this probably indicates that the birdshot lesions lie deep
in the choroid. Indocyanine green angiography shows many
more lesions in the choroid than are seen clinically. The disease
follows a remitting course over many years; visual acuity is lost as
a result of macular oedema or sub retinal neovascularization. The
main differential diagnosis is sarcoid.
 WHITE SPOT SYNDROMES 32

depigmented
birdshot lesions

Fig. 10.86 There is mild disc swelling with multiple areas of depigmentation
one-third to one-half a disc in diameter throughout the posterior pole. A feature of
note is that these areas are never associated with any pigmentation.

retinal vessels
distorted by rt--'-0r"'t¥'>7/*-c::Y~
preretinal membrane
leakage

Fig. 10.87 In contrast to other types of white spot syndrome, fluorescein

angiography is often normal over the site of individual lesions. Optic disc leakage
and macular oedema are common.

characteristic ,-----~---.::-.-,----w~-----,
depigmented f----c-----,""~~'1
foca l lesions

Fig. 10.88 This is the same patient seen six years later. More areas of choroidal depigmentation can be seen.
8 INTRAOCULAR INFLAMMATION

MULTIPLE EVANESCENT WHITE DOT SYNDROME {MEWDS}

This is a rare unilateral condition that typically affects young
females. Affected patients present with visual loss, photopsia and
temporal or paracentral scotomas, often with enlargement of the
blind spot. Characteristically multiple small white lesions
100-200 11m in diameter are seen at the level of the outer retina
and RPE throughout the posterior pole, some of which show
hyperfluorescence on fluorescein angiography. There is a mild
posterior uveitis. The disease is monophasic and the lesions and
symptoms resolve over a few weeks leaving a normal retina. The
disease has some similarities with the big blind spot syndrome
and acute zonal occult outer retinopathy and they may all be part
of the spectrum of the same disorder.

Fig. 10.89 Multiple small white lesions are seen throughout the posterior pole in
this otherwise healthy 23-year-old woman who presented with a large blind spot and
photopsia.
By courtesy of Dr F X Borruat.

Fig. 10.90 Some lesions show mild hyperfluorescence at the level of the RPE but many more lesions are seen on indocyanine green
angiography.
By courtesy of Dr F X Borruat.
 MASQUERADE SYNDROMES 3

MASQUERADE SYNDROMES

A number of noninflammatory diseases can simulate posterior present in this way include retinoblastoma in children and ocular
uveitis. These should always be considered in cases where there lymphoma in adults. Intraocular bacterial or fungal infection may
is a progressive deterioration of the eye in spite of appropriate also present as a posterior uveitis.
anti-inflammatory treatment. Malignant diseases that can

OCULAR LYMPHOMA

Patients present with blurred vision and floaters and unilateral
or bilateral posterior uveitis. The diagnosis should be
considered particularly in patients with AIDS or the more
elderly patient where there is failure to respond to a
therapeutic course of systemic steroids. Some patients will have
focal subretinal lesions but in others there is only a diffuse
posterior uveitis. The diagnosis is confirmed by vitreous
aspiration with cytological examination. Patients often have
concurrent second eye or CNS involvement. Ocular
involvement responds to radiotherapy but patients have a high
risk of developing intracranial lymphoma. Ocular lymphoma
can be due to either B or T cell lymphomas, although the
former is much more common.

subretinal masses

Fig. 10.91 This patient presented with posterior uveitis and subretinal infiltrates. He
was treated with systemic steroids but the ocular signs continued to deteriorate.

Fig. 10.92 Two months after these photographs were taken, the patient presented with
intracranial focal lesions; lymphoma cells were recovered from the CSF.
30 INTRAOCULAR INFLAMMATION

Fig. 10.93 Ocular pathology shows the retina and choroid have
been destroyed and densely infiltrated by lymphoma cells (large
neoplastic B-lymphocytes) .

OCULAR CANDIDIASIS

This condition is seen in severely ill patients who have had
multiple antibiotic treatment and long-standing intravenous
catheters (which should be cultured in suspected cases).
Intravenous drug users are also at risk. Systemic evidence of
infection is usually absent but it is important to take blood
cultures and to perform echocardiography and take blood
cultures to exclude valvular endocarditis. The initial lesion
originates as an embolic focus in a choroidal vessel that bursts
through into the retina and then the vitreous, and replicates
there to form fluffy white masses in the posterior vitreous.
These sometimes have the appearance of being linked
together and are known as the 'string of pearls' sign. Patients
present with floaters, blurred vision and posterior uveitis.
Diagnosis is made by culture of the yeast following
vitrectomy, which also clears the gel and removes the scaffold.
Antifungal agents are given intravitreally and systemically.

Fig. 10.94 This patient developed bilateral candida endophthalmitis after

intensive care with prolonged intravenous feeding following multiple abdominal
surgical procedures.

foci of ca ndida '---'~­

in vitreous

preretinal lesion

Fig. 10.95 In the right eye there is a hazy vitreous with foci of Candida. A
whiter lesion can be seen attached to the retinal surface adjacent to the
macula.
 MASQUERADE SYNDROMES 3:!

choroidal inflammation

Fig. 10.96 Histological appearance of an eye with Candida chorioretinitis. The

fungus is thought to seed in the choroid and then break through into the retina and
mushroom on the surface.
By courtesy of Professor S Lightman.
The Lens
David Spalton

Development and Growth of the Lens

Accommodation
Anomalies of Shape and Position
Cataract
Progress and Prognosis of Cataract
Cataracts and Systemic Disease
Paediatric Cataract
Complications of Cataract Surgery
 DEVELOPMENT AND GROWTH OF THE LENS

The lens is an unique organ in that its epithelium is inverted so
that the cell apices face internally with their base lying on the
basement membrane that encapsulates the lens (the capsule). It
is not innervated and lacks a blood supply after regression of the
tunica vasculosa lentis so that nourishment must come through
the aqueous and vitreous. The lens grows throughout life by
continuous mitosis in the equatorial epithelium, these cells
mature into lens fibres. There is no means to shed fibres or
catabolize protein yet the lens must remain transparent. New
fibres are constantly produced and move centrally with each
generation, and as they do so their cell nucleus is lost and the
protein is compacted. The lens contains a very high concentration
of protein, about 30% of its weight. Most of the protein is soluble
and comprises the a and ~y crystallins. a Crystallin has a
chaperon function whereby it binds denatured proteins and
prevents the formation of large aggregates which would scatter
light.-The insoluble proportion of these proteins increases with
age and their concentration increases from the cortex to the
nucleus, accounting for the increased refractive index in the
nucleus. Glucose metabolism is conducted by anaerobic
pathways.

a b c

Lens placode Lens pit

d e

vasculosa
len t is
Early lens vesicle Late lens vesicle

Fig. 11.1 Recently there has been considerable research on the genetic control of lens development and on the growth factors such as
fibroblast growth factor and insulin-like growth factor that modulate the development of the lens vesicle and its invagination into the optic
vesicle. The lens placode differentiates from the surface ectoderm at the 4-mm stage (about 3 weeks after conception). By 14 mm (6 weeks)
it has separated from the surface ectoderm to form the lens vesicle and the embryonic lens nucleus then begins to form. The lens is
supported by the tunica vasculosa lentis which is derived from the hyaloid vascular system. This blood supply is fully formed by 3 months'
gestation after which it begins to atrophy and has disappeared by the end of the seventh month of gestation.

6
- Whole lens
5 - Nucleus
- Cortex
'E 4
5
...,
.I:: 3
-a
~ 2
Fig. 11.2 A normal lens increases in thickness with age. The
observed increase is the sum of growth by fibre accretion and
central compaction. Increasing thickness is largely the result of
0+----,----,----,----.----.----.----.--~
cortical growth; lenses that develop cataract tend to be smaller
0 10 20 30 40 50 60 70 80
than their age-matched norm until the onset of hydration with
Age (years) maturity.
 DEVELOPMENT AND GROWTH OF THE LENS

cortex

nucleus

Fig. 11.3 These Scheimphlug images compare the lens of a 10-year-old child with that of an elderly person. In the child the lens is
composed largely of nucleus, the cortex being represented only by a thin bright band. The lens in the older person is greatly increased in
thickness due almost entirely to growth of the cortex with the nucleus remaining almost unchanged . The scattering properties of the lens
are greatly increased in the elderly so that the lens appears to be brighter; in addition the radii of curvature of its surfaces, particularly the
anterior surface, are reduced so that the lens becomes more convex.
By courtesy of Mr N Phelps Brown.

17

E' 15
5
~ 13
...
:l

"'2:
:l
11
Fig. 11.4 The radius of curvature of the anterior surface of the
u lens becomes progressively shorter with age (i.e. more convex),
....0 resulting in increased postive spherical aberration (see Ch. 1). The
9
"'
:l cornea has a positive spherical aberration too so that with age there
"0
"'
C<:
7 is increasing aberration which leads to image degradation and loss
of contrast. This is of some interest as intraocular lenses are now
5 being manufactured with a negative spherical aberration to
0 10 20 30 40 50 60 70 80
neutralize the corneal aberration leading to better contrast post-
Age (years) operatively.
 Fig. 11.5 This histological section shows the anterior surface of
the lens at the equator. The capsule appears structureless and
stains weakly. It is the basement membrane of the lens epithelium
and consists of type 4 collagen. It varies in thickness between 10
and 20 f..Lm and is thinnest at the anterior and posterior poles and
the equator. The lens epithelium, which is present only anteriorly,
is composed of a single layer of nucleated cells. It is responsible for
the continual production of new lens fibres which are seen to be
separating from the epithelial layer in the lower part of the figure .
Although the young fibres are nucleated they eventually lose their
nuclei as they sink into the cortex.

Fig. 11 .6 Lens fibres are hexagonal in shape and lie in layers

rather like the skin of an onion. Individual fibres are connected to
Anterior one another by 'ball and socket' interdigitations. Initially they are
epithelium attached to the capsule anteriorly and posteriorly (their basement
membrane). With time and the formation of new fibres they lose
their capsular attachments, their nuclei and interdigitations and
cell membranes to become compacted as insoluble protein in the
Anterior pole Posterior pole
n u cleus.

• Anterior Y suture
l!l!l Posterior Y sutu re

Fig. 11.7 Each fibre is a long ribbon-like structure with ends that
stretch to each anterior and posterior pole where they meet a
fellow fibre from the opposite side. If the system was completely
symmetrical they would meet at a single point but this is not the
case and they meet one another in a complicated branching system
known as suture lines . The suture lines of the fetal nucleus are
easily seen in the normal adult lens as an erect Y anteriorly and an
inverted Y posteriorly. With increasing age the sutures become a
more complex branching system extending out into the cortex,
each lens fibre running anteroposteriorly across the equator of the
lens and interdigitating with its neighbours.

ACCOMMODATION
By contraction of the ciliary muscle (under parasympathetic 3rd
nerve supply) the lens changes shape and increases its diopteric
power to focus near objects on the retina. The physiological basis
of accommodation was developed by Helmholtz and his theory
has been confirmed by many observations since then. The
increase in diopteric strength of the lens is largely accounted for
by a shortening in radius of curvature (increased convexity) of
the central part of the anterior surface which also moves forward
slightly. The curvature of the lens, which at rest is close to
spherical, becomes more conoid on accommodation. This
aspherical change appears to be brought about by a difference in
Fig. 11.9 (Left) Zonular fibres can be seen inserting into the lens capule from between the ciliary processes (right) .
By courtesy of Professor John Marshall.
ACCOMMODATION
lens suture
Fig. 11.8 The lens sutures are clearly seen by retroillumination
in this example of early traumatic cataract due to a metallic foreign
body.
behaviour between the nucleus and the cortex; the nucleus
undergoes the greater change and distends the anterior axial
capsule which is comparatively weaker centrally. The force
required to change the shape of the lens comes from the capsular
elasticity which moulds the lens by its elastic force as the tension
from the suspensory zonules on the capsule changes.
Accommodation is measured in dioptres, thus ID of
accommodation is needed to focus from infinity to 1 m or 3D to
focus at 33 em. A child has as much as 14D of accommodation
but by 60 years of age this has virtually disappeared.

ANOMALIES OF SHAPE AND POSITION
Anomalies of lens shape and position are rare disorders either
resulting from primary lens pathology or due to secondary
zonular changes. They are either genetic (in which case there may
be other systemic abnormalities) or a result of trauma or pseudo
lens exfoliation, which is associated with zonular weakness. Pupil
anterior lenticonu s
cornea
more convex
anteri or surface
nucleus nucleus
anteriorly
displaced
Fig. 11.10 These slit-image Scheimphlug photographs show the
changes in a 30-year-old lens focused at infinity (left) and exerting
1OD of accommodation (right). The increased curvature of the
anterior lens surface and its slight anterior positioning can be seen
clearly. The posterior lens surface remains relatively unchanged.
By courtesy of Mr N Phelps B rown.
block glaucoma is a common feature of subluxating or dislocating
lenses (see Ch. 8). Intact lenses that dislocate posteriorly can lie
in the vitreous or on the retinal surface for many years without
causing ocular damage.
Fig. 11.11 Anterior lenticonus is a
feature of Alport's syndrome. This is a
dominant disorder of variable
penetrance that is due to a basement
membrane defect. As well as the lens
defect, which causes irregular
astigmatism, the condition is associated
with renal failure and neuronal
deafness. Patients may have an
associated retinopathy of white inner
retinal flecks .
 ANOMALIES OF SHAPE AN

Fig. 11.12 Spherophakia is seen in a number of conditions in

which the lens has an abnormally short radius of curvature and
may also be exceptionally small (microphakia). Extreme myopia
results. Although this lens is normally situated, there is usually a
tendency for lenses to subluxate and dislocate anteriorly.
By courtesy of Mr N Phelps Brown.

Fig. 11.13 The Weil-Marchesani syndrome is inherited recessively and characterized by short stature and stubby fingers (left) and toes
(right), which have stiff joints. Spherophakia, lenticular myopia of 10-20D and lens dislocation are common. Heterozygotes may show a
milder form of the disease.

subluxated lens

Fig. 11.14 Marfan's syndrome is a dominantly inherited disorder

that affects the eye, skeleton and cardiovascular system. It is due to
a deficiency of fibrillin, a component of the microfibrillar system
associated with elastin and encoded on chromosome 15q. The lens
tends to dislocate upwards (in contrast to homocystinuria where it
dislocates inferiorly). The lens is more spherical, causing myopia
with marked astigmatism. Management of these patients has been
transformed by a complex procedure of lens removal, placement of
a sclerally sutured endocapsular ring to recentre the bag and IOL
implantation.
 CATARACT

A cataract is any opacity within the lens. Cataracts are classified
according to their morphology and position within the lens and
graded by the degree of opacity or 'maturity' produced. If lens
damage is insufficient to progress to maturity a localized opacity
is produced in the injured region that becomes surrounded by
new lens fibres as they are laid down beneath the capsule (see
glaucomflecken Ch. 7). The three major types of age-related
cataract are nuclear, cortical and posterior subcapsular opacity;
many patients have combinations of these . It has been suggested
that these represent different disease processes: nuclear changes
being caused by protein denaturation, cortical by damage to lens
fibres and posterior subcapsular cataract by migration of lens
epithelial cells posteriorly. This remains to be proven.
Occasionally the morphology of a cataract may give an indication
of its aetiology (e.g. posterior subcapsular cataract with trauma or
steroids) and this may have important medicolegal implications.
The morphology does, however, influence the patient's
symptomatology.
Genetic factors have shown to be important risk factors for
age related nuclear and cortical opacity; other recognized
cataractogenic environmental ris.ks are sunlight, smoking,
dehydration and chronic diarrhoea (Table 11.1).

Table 11.1 Causes of cataract

Congenita l
Maternal infection (e.g. rubella )
Genetic
Metabol ic (e.g . galactosaemia)
Chromosoma l (e.g. Down's syndrome)
Ocular developmental (e.g. Pet ers' anomaly)
Trauma
Acqu ired
Age related
Metabolic (diabetes, hypothyroidism, atopy)
Drugs (steroids)
Intraocular disease (uveitis, retinitis pigmentosa)
Trauma (blunt injury, radiotherapy, intraocular surgery)
Genetic (age related nuclear and cortical, Dystrophia myotonica)

Fig. 11.18 This diagram illustrates the different m orphological

• Subcapsular (cupuliform) D Cortical (cuneiform) Sutural [] Anterior
[] Supranuclear (coronary) D Nuclear (lamellar) D Nuclear polar
patterns of cataract together with their depth and location within
the lens.

CAPSULAR CATARACT

Capsular cataracts are a relatively uncommon type of cataract Posterior polar cataracts in children are frequently associated
that may be either congenital or, less frequently, acquired in later with a defect in the posterior polar capsule and this is of
life. Those involving the anterior pole seldom require treatment considerable surgical importance.
as they are unlikely to interfere with vision to any great extent.
 persistent
pupillary membrane

iris collarette

Fig. 11.19 Anterior polar capsular opacity is usually congenital. It can lie flat on the surface or protrude from the lens forwards as a small
pyramid (top); sometimes remnants of a persistent pupillary membrane are present (bottom). Underlying lens fibres are affected and may
produce an appearance similar to a stack of plates in the anterior cortex. The defect appears to be due to failure of lens fibres to meet and
interdigitate at the anterior pole. Anterior polar opacities do not affect visual acuity as severely as those in the posterior pole which lie
closer to the nodal point of the eye.

subepithelial
opacity

Fig. 11.20 Following prolonged use of high doses of

chlorpromazine in psychiatric treatment a characteristic pigmented
deposit appears on the capsule with a star-shaped cataract in the
subepithelial fibres outlining the lens sutures. This patient also had
increased cutaneous and corneal pigmentation, a well recognized
feature of long-term phenothiazine treatment.

SUBCAPSULAR CATARACT
Subcapsular cataracts are usually seen at the posterior pole.
Patients tend to have relatively good distance acuity in low light
conditions but very reduced near vision with marked glare in
bright light or with night driving as the opacity is situated
centrally on the visual axis near the nodal point. Posterior
subcapsular cataract can be seen as an isolated opacity or in
Fig. 11.21 Posterior subcapsular changes start as a polychromic lustre of the cortex adjacent to the posterior capsule progressing to a
greyish granular opacity. The subjacent cortex often contains opacities. These deeper cortical opacities are a sign of long-standing changes
and were themselves subcapsular at the time of their formation.
By courtesy of Mr N Phelps Brown.
CATARACT
combination with other types of age-related cataract. It is the
typical cataract of intraocular disease (high myopia, uveitis, etc.),
trauma or drugs but the cause cannot be established from the
ocular appearances in isolation. It is caused by the posterior
migration of lens epithelial cells from the equator.
posterior
subcapsu lar opacity
deeper
cortical opacities
posterior polar
cataract
Fig. 11.22 This is a discrete dense posterior polar cattaract.
These are often associated with a weakened or deficient posterior
capsule which is of considerable surgical importance.
 Dilated pupil

a
a'

Contracted pupil

a Fig. 11.23 The position of a posterior subcapsular cataract on

a' the visual axis has a very destructive effect on vision as it lies near
the nodal point of the eye so that light must pass through this
point. Pupillary constriction in bright light enhances this effect
because the reduced aperture prevents the entrance of the more
peripheral and less affected rays.

TRAUMATIC SUBCAPSULAR CHANGES

Posterior subcapsular cataract is frequently seen after ocular severe blunt trauma and a unilateral cataract should always raise
injury. If the damage is severe, cataract forms quickly and the possibility of previous trauma.
progresses rapidly. Cataract can develop many years after less

Fig. 11.24 Star-shaped cataracts at the posterior pole are a typical but uncommon sign of blunt injury which more commonly produces
just posterior subcapsular lens opacity. A possible explanation_ of the appearance is that the superficial lens cortex r.u:g.tur.es at the suture line
allowing fluid into the fibre tips which then spreads up the fibre before the defect is sealed.
 CATARACT

posterior
subcapsular
cataract
granular opacities

· ---
posterior subcapsular
plaque
7...

Fig. 11.25 Radiation cataract results from injury to the lens by ionizing radiation (X-rays, P-rays, y-rays and neutrons); about 4 Gy is
sufficient to produce a cataract. It begins as a centripetal streaming of granular particles in the posterior subcapsular zone (left) , which
form a plaque of opacities at the posterior pole. After severe irradiation the cataract deteriorates to maturity but with more minor
irradiation the cataract eventually becomes a static discrete opacity which comes to lie deeper in the lens with time (right) .

CORTICAL CATARACTS

Cortical cataracts are common. They are caused by damage to a

group of lens fibres and are seen as radial wedge-shaped
opacities. Their size and position means that they produce little
visual impairment until the visual axis is affected when the
patient notices glare and loss of contrast.

Fig. 11.26 Spoke, or cuneiform, cataracts are a relatively

common form of senile opacity that lie in radial wedge shapes at
about mid-depth in the cortex. They form peripherally and
produce symptoms when they extend into the pupillary area.

Fig. 11.27 Congenital blue dot or punctate opacities are seen as

discrete punctate opacities with a bluish colour throughout the
cortex. They have little effect on vision and are often found
coincidentally on routine examination, although patients tend to
develop presenile cataract.
THE LENS
Fig. 11.28 While punctate cataracts are usually situated in the
cortex, they may also be seen within the nucleus if opacity
formation began either in utero or in infancy.
By courtsey of Mr N Phelps Brown.
NUCLEAR CATARACTS
Nuclear cataracts occur at the two extremes of life. In the very
young they are rare and their effect on vision may diminish with
time if normal clear lens is laid down around the cataract. They
are very common in old age. Nuclear cataracts show
opalescence from protein aggregation and light scattering and
brunescence from protein denaturation which causes loss of
spo ke opacities
Fig. 11.29 Coronary cataracts are spoke opacities in the
peripheral lens that do not affect vision. When viewed by
retroillumination the cataract is seen to form a crown (corona)
around the nucleus. This form of cortical cataract may be
developmental and nonprogressive .
Fig. 11.30 Sutural cataract is usually congenital in origin and
inherited in an X-linked manner. The tips of the lens fibres opacify
as they insert into the suture lines demonstrating the lenticular
anatomy.
transparency. Nuclear cataract develops very commonly about
1- 2 years after vitrectomy; this has recently been shown to be
due to increased oxygen concentration in the vitreous cavity
after surgery. Nuclear cataract causes blurred distance vision
from opacity and refractive changes; near vision is often
preserved until much later.
 CATARACT

nuclear sclerosis

Fig. 11.31 The common age-related nuclear cataract is seen as a

central opalescence in the lens that scatters light.

nuclear sclerosis

Fig. 11.32 Nuclear cataracts also show increasing brunescent pigmentation from yellow through to dark brown. This is an important
physical sign as brunescence correlates well with increasing lens hardness and hence more phaco power is required for removal.
Brunescence absorbs as well as scatters light and alters the patient's colour perception; this may have a beneficial effect as it protects the
macula from short wavelength blue light which is thought to be a risk factor in age-related macular degeneration. Increasing brunescence
lowers visual performance at low light levels and alters colour perception. This is thought to explain why artists such as Turner and
Rembrandt used a predominance of orange, red and brown colours in their later paintings.
By courtesy of Mr N Phelps Brown.
THE LENS

Fig. 11.33 In congenital cataract the extent to which the nucleus

is affected depends on the duration of cataract formation in utero.
The embryonal nuclear cataract, cataracta centralis pulverulenta -
or Coppock cataract after the family in which it was first described
- consists of a small grey opacity in the embryonal nucleus. It is
embryonal
nuclear cata ract bilateral and dominantly inherited and does not interfere with
vision because of its small size. The genetics are well understood
and the condition is due to expression of an abnormal y-crystallin
in the prenatal period.

lamell ar cataract

Fig. 11.34 Lamellar cataract affects a layer of lens fibres damaged by an insult for a limited period of time. It is usually seen as a nuclear
opacity that is congenital in origin although when first formed the cataract is actually subcapsular and moves deeper into the lens as norma
new fibres are laid down over it. If the precipitating cause continues to a lesser extent individual groups of fibres are subsequently affected
and are seen as 'riders' over the main opacity.
 PROGRESS AND PROGNOSIS OF CATARACT

Fig. 11.36 The commonest cause of congenital cataracts used to

be maternal rubella infection occurring during the first trimester of
pregnancy. Fortunately the incidence of this infection has declined
dramatically as a result of immunization of the female population.
concentric
Affected infants have active virus infection in the eye and raised
lamellar opacities titres of rubella antibody in the blood. Other signs of the disease
are frequently present as in this 2-year-old child who had bilateral
nerve deafness, microcephaly, severe intellectual impairment and a
congenital heart defect. Some patients also have retinopathy (see
Ch. 16).

Fig. 11.35 Scheimphlug photography in this lens shows two

affected concentric lamellae.
By courtesy of Mr N Phelps Brown.

PROG RE SS AND PROGNOSIS O F CATARACT

Cataracts cause blurring, glare and loss of contrast. The degree of
visual blurring depends on the site of the opacity within the lens,
its density and its proximity to the visual axis. Glare is produced
by light scattering and can be a disabling symptom. This can be
assessed by testing visual acuity or contrast sensitivity with and
without an illuminated glare-producing surround on the chart.
Monocular diplopia and ghosting of the image results from
changes in refractive index within the lens. In addition, higher
order aberrations will produce monochromatic haloes and
distortion, and brunescence will affect the patient's vision in low
light conditions and colour discrimination.

4
- Right
3 - Left

2
~
ill
.s::
a.
Vl

0 Fig. 11.37 In the normal ageing eye there is gradual shift

towards hyperopia with age but lenses developing nuclear cataract
-1 shift towards myopia which frequently preceeds diagnosis of the
cataract. This is caused by increased lens thickness and swelling.
-2
1990 1995 2000 2005 This graph shows the spherical equivalent in a patient followed for
many years. Increasing hyperopia is seen until the development of a
Year
cataract in the right eye when there is a rapid myopic shift.
THE LENS

Fig. 11.38 A cataract is said to be mature when all fibres are opacified up to the capsule (a); this is associated with water entry into the
lens by osmosis and swelling. The Scheimphlug image of another patient (b) shows water clefts, seen as dark areas between fibre lamellae.
By courtesy of Mr N Phelps Brown.

conjunctival injection

cornea l oedema

Fig. 11.39 The maturing lens, even in young subjects, can

become intumescent to such a degree that it causes shallowing of
the anterior chamber, pupil block and closed-angle glaucoma.
Phacolytic glaucoma can also result from leakage of lens protein
into the anterior chamber (see Ch. 8).
 CATARACTS AND SYSTEMIC DISEASE

calcific fla kes

sunken nucleus

Fig. 11.40 If the cortex liquifies, the nucleus may sink inferiorly
(Morgagnian cataract) and can be mistaken for a subluxated lens.

absorbed lens
material

absorbing
cataract

calcific remn ant

Fig. 11.41 With more time the liquified cortex will absorb,
leaving a calcific nuclear remnant. This can be very tough and
adherent to the capsule and very difficult to remove .

CATARACTS AND SYSTEMIC DISEASE

The vast majority of adult cataracts occur m the absence of developed countries and cataract may be the presenting sign. All
~'istemic disease. Diabetes is the commonest association in other systemic associations are rare .

eczematous skin

Fig. 11.42 This young woman has cataracts associated with

severe chronic eczema, possibly exacerbated by steroids used to
control the disease. She has had recent surgery to the right eye; the
left has a mature cataract. Such patients have an increased risk of
postoperative bacterial endophthalmitis from the skin disease.
2 THE LENS
PAEDIATRIC CATARACT
Congenital and infantile cataract is associated with a myriad of
rare genetic and metabolic causes, as well as more common
causes (see Table 11.1) . Most congenital cataracts are picked up
by routine screening of healthy neonates when there is no red
reflex or as a dense spot against the red reflex on ophthal-
moscopy, as a non-seeing baby, as a squint or on routine
surveillance of children with a predisposing risk. Most paediatric
Fig. 11.43 Dystrophia myotonica is a dominantly inherited
condition commonly associated with cataract. This disease
increases in severity with successive generations. This patient has
the typical facial appearance. Notice the frontal balding, wasting of
the temporalis muscles and evidence of external ocular myopathy
with bilateral ptosis. Characteristically polychromatic glistening
granules start to appear during the teenage years in the
subcapsular and cortical areas and progress to posterior
subcapsular changes and maturity. These opacities can be a useful
genetic marker although the lens is sometimes unaffected in people
who have overt disease. Myopathy of the respiratory muscles can
make general anaesthesia hazardous.
cataracts are suitable for IOL implantation the major
contraindication being paediatric uve1t1s. Ophthalmic
management brings together the problems of challenging
surgery, refractive correction in a developing eye, amblyopia and
posterior capsule opacification often in the context of a multiply
handicapped child.
Fig. 11.44 As well as having a mature cataract the right eye of
this child is convergent, and microphthalmic. He had rubella
retinopathy in the left eye. Ultrasonography is required to eliminate
posterior segment pathology in the right eye. In this situation
successful visual results from surgery are extremely rare because of
the insuperable problems of coexisting eye disease, optical
correction and treatment of amblyopia. Treatment is therefore
cosmetic.
 COMPLICATIONS OF CATARACT SURGERY

COMPLICATIONS OF CATARACT SURGERY

Cataract surgery accounts for about 70 per cent of all ophthalmic
surgery. In Western countries about 4 to 6 operations are
performed per 1000 population; this equates to about 1 million
operations a year in the USA and the number is forecast to rise
as a result of increasing surgical success justifying earlier
intervention and increasing longevity of the population. Serious
complications are rare but because of the vast amount of surgery
being performed even rare complications affect a lot of people.
Complications of phaco-emulsification surgery can be divided
into operative and early or late postoperative (more than 3
months after operation) (Table 11.2). The most serious
complications arise from infection, posterior segment
complications and the consequences of posterior capsular
rupture.

Table 11.2 Complications of phaco-emulsification surgery

Operative Early postoperative Late postoperative
Phaco wound burn* lnfecti ont IOL decentration*
Iris touch* Wound lea kt Posterior capsule opacification*
Corneal touch* Ra ised intraocular pressure Inadequate refractive correction*
Rhexis tear* Iritis Retinal detachmentt
Zonular dialysis* Medication al lergy Corneal endothelial failuret
Posterior capsule ruptu ret Retained lens materi al* Failu re of previous trabeculectomy*
Dropped nucleust Pseu dophakic cystoid macular oedema*
Vitreous losst
Choroidal haemorrhage
Induced astigmatism

*Serious complication; t potentially sight-threatening complication.

OPERATIVE COMPLICATIONS

fish mouthing
of phaco wo und w hit e coagulated
collagen

Fig. 11.45 Corneal wound burn has come into prominence with the advent of small-incision clear corneal phaco-emulsification surgery.
It is caused by a failure of aspiration, too tight a wound or too much phaco power. Heat is transmitted to the wound causing collagen
shrinkage, fish mouthing and defective closure and leading to increased postoperative astigmatism and a risk of postoperative
endophthalmitis.
Courtesy of Mr D Smerdon
4 THE LENS

Fig. 11.46 Choroidal haemorrhage is a rare but very serious

intra operative complication occuring more commonly in
hypertensive patients and exacerbated if the patient is
anticoagulated. The eye suddenly develops a shallow anterior
chamber and high intraocular pressure.
By courtesy of Mr B Damato

Fig. 11.47 Rupture of the posterior capsule during phaco-

emulsification can lead to loss of nuclear fragments into the
vitreous cavity followed by uveitis, glaucoma and corneal
decompensation. Fragments are best removed by a formal vitreo
retinal procedure.
By courtesy of Mr T Williamson

Fig. 11.48 The iris can be damaged either by touch with the phaco tip or from prolapse into the wound. This patient had an iris prolapse
through too large a side port incision during the procedure resulting in loss of the pigment epithelium with the potential risk of pupillary
distortion, iris translucency and synechiae.
 COMPLICATIONS OF CATARACT SURGERY 35

EARLY POSTOPERATIVE COMPLICATIONS

peaked pupi l

fresh blood

ciliary injecti on

Fig. 11.49 Wound-related problems have largely disappeared with the change from extracapsular to phaco-emulsification surgery. Iris
prolapse (top left) results from poor surgical technique, Valsalva manoeuvre or pressure on the eye; extensive hyphemas (top right) may be
associated with raised pressure or corneal blood staining. Ultrasonography to delineate the intraocular anatomy is indispensable if further
surgery is contemplated. Rupture of sutures occurs 1-2 years after surgery when the nylon digests and erodes through the epithelium
(bottom left). Patients present with a foreign body sensation and a red discharging eye.
6 THE LENS

blood and fibri

posterior on IOL
synechiae

red eye iris naevus

Fig. 11.50 Current rates of postoperative bacterial endophthalmitis are in the order of 2 per 1000 surgeries. After surgery a patient
should have a progressively whiter and more comfortable eye with improving vision. Increasing pain, photophobia and redness suggest
endophthalmitis. Such patients need to be seen as an acute emergency and, if examination confirms the diagnosis, require a vitreous tap for
bacterial culture and intraviteal antibiotics. This patient presented 2 weeks after surgery. The vitreal tap grew a fully sensitive coagulase-
negative staphlococcus.

conjunctival soft lens

naevus matter
fragment of
nucleus

Fig. 11.51 Nuclear fragments (left) left in the eye after surgery will
cause inflammation and glaucoma and must be removed. Soft lens matter (right) may be absorbed spontaneously if there is a limited
amount but patients need to remain under observation until it has disappeared completely.
 COMPLICATIONS OF CATARACT SURGERY 3

post peaked pupil

synechiae

fibrin

Fig. 11.52 A fibrinous reaction after routine surgery is unusual unless the operation was traumatic. This patient suffered iris damage
when the operation was converted from phaco-emulsification to an extracapsular procedure. The anterior chamber cleared on treatment
with topical steroids and mydriatics.

posterior
synechiae

Fig. 11.53 Postoperative inflammation can cause a foreign-body giant cell reaction to the IOL. This seen most commonly with
hydrophobic IOL materials as pigmented multinucleate cells on the anterior IOL surface and eyes with large numbers of cells (left) have a
high incidence of posterior synechiae and cystoid macular oedema. Giant cells are often seen adjacent to posterior synechiae (right) . The
cells gradually reduce over many months with treatment or as the inflammation resolves.
THE LENS

posterior
synechiae

giant cells
IOL anterior
to iris

Fig. 11.54 Pupil capture of the IOL is another manifestation of

prolonged postoperative uveitis.

Suture too tight.

Steeper vertical axis
(with the rule astigmatism)

Suture too loose.

Steeper horizontal axis
(aga inst the rule
vitreous band
astigmatism)

peaked pupil
i

Fig. 11.55 Vitreous loss with entrapment in the wound and

distortion of the pupil occurs from dialysis of the zonule or rupture
of the posterior capsule at the time of surgery and an inadequate
vitrectomy. Such eyes carry a risk of prolonged inflammation,
cystoid macular oedema and retinal detachment. Small bands such
as this can be cut with a YAG laser.
'
Fig. 11.56 Suturing of the phaco wound can induce astigmatic
changes in the cornea.
 COMPLICATIONS OF CATARACT SURGERY 35!

iris clip IOL

corneal oedema

Fig. 11.57 C orneal oedema can result from damage to the corneal endothelium as a result of excessive phaco power or endothelial touch
during surgery, from the instillation of incorrect solutions at operation because of a failure in procedure, from decompensation of a pre-
existing endothelial dystrophy such as Fuchs' dystrophy (see Ch. 6) or long-term endothelial touch from an anterior chamber lens in which
case endothelial failure occurs many years later. In this eye with an iris clip lens the superior corneal endothelium was probably damaged
during implant insertion leading to corneal oedema 5 years later.

anterior capsu lar

f ibrosis
decentred IOL

Fig. 11.58 Postoperative capsular fibrosis from a contracting

capsular bag (often in association with a torn or asymmetrical
rhexis or pseudoexfoliation of the lens capsule) can displace and
decentre the IOL. This patient, who had had a phaco
trabeculectomy, presented with difficulty with night driving.
Examination shows a mildly decentred PMMA IOL, bringing the
lens edge into the visual axis with mydriasis.

iris defect

subluxed IOL

Fig. 11.59 This patient had a secondary sulcus placed IOL

following a traumatic injury and broad iridectomy some years
previously which subluxated inferiorly soon after surgery from
unrecognized previous zonular dialysis. The IOL was repositioned
and fixated with a scleral suture technique .
60 THE LENS

capsular f ibrosis

Fig. 11.60 Capsular phimosis is caused by excessive anterior

capsular fibrosis. It can lead to blurred vision, glare or poor night
vision. It is most commonly seen with pseudo lens exfoliation or
some types of hydrophobic lens materials.

Elschnig's pearl s YAG capsulotomy

rhexis on
anterior IOL
surface

Fig. 11.61 Posterior capsule opacification (top left) is the commonest complication of routine phaco-emulsification surgery. It is caused
by migration of the residual lens epithelial cells, inevitably left at the time of surgery, from the equator over the posterior capsule producing
symptoms similar to those of the previous cataract 1-2 years later. The problem is easily treated by laser capsulotomy (top right), but this
carries a small risk of medical complications and is inconvenient and expensive. The use of IOLs with a square edge profile (bottom left)
inhibits this process and the rates of this complication are starting to fall significantly as a result.
 COMPLICATIONS OF CATARACT SURGERY

peripheral
iridectomy

erosion of iris
stroma by loop
L_-=~~~~~~L_~~--~~~

Fig. 11.62 The IOL, especially if placed in the sulcus, can chafe the iris or iris pigment epithelium resulting in uveitis, pigmentary
glaucoma or recurrent hyphema (the UGH syndrome). This was a particular problem with iris clip IOLs which chaffed on the iris surface.
This patient presented with recurrent hyphema. Two years later this produced a full-thickness hole and the symptoms resolved.

retroillumunation
showing loss of iri s
pigment epithelium

Fig. 11.63 In another patient a posterior chamber sulcus placed IOL can be seen on retroillumination to chaff the iris pigment
epithelium. This patient had pigmentary glaucoma.
 leakage from
optic disc

early leakage from

perifoveal capillaries petalloid pooling of rR/--~-J.~f:P
fluorescein in late
phases of angiogram

Fig. 11.64 Visually significant pseudo-phakic cystoid macular oedema occurs in 1-2 per cent of patients after surgery and subclinical
changes may be seen on fluorescein angiography in many more patients. Most patients have transient symptoms, but a few have permanent
visual loss. Treatment with topical steroids and a nonsteroidal agent such as ketorolac for 3 months leads to resolution in the majority of
cases.

Fig. 11.65 If, for some reason, an IOL cannot be inserted the
postoperative aphakic must be corrected by means of glasses or
contact lenses. Aphakic glasses magnify by 30 per cent; they
produce visual distortion from spherical aberration and a restricted
visual field from the prismatic effects of the lens, which also
produces a roving 'Jack-in-the-box' scotomatous effect. Contact
lenses produce about 4-5 per cent magnification and allow fusion
in a monocular aphakic patient at the expense of the problems of
contact lens management.
Vitreous and
Vitreoreti na I
Disorders
Thomas Williamson

Anatomy and Embryology of the Vitreous

Vitreous Changes
Rhegmatogenous Retinal Detachment
Differential Diagnosis of Rhegmatogenous Retinal Detachment
Special Types of Rhegmatogenous Retinal Detachment
Intraocular Foreign Bodies
Extraretinal Neovascularization
Macular Vitreoretinal Pathology
Macular Epiretinal Membrane (Pucker)
Principles of Vitreoretinal Surgery for Rhegmatogenous Retinal Detachment
 s

ANATOMY AND EMBRYOLOGY OF THE VITREOUS

The vitreous cavity is the space bounded anteriorly by the lens
and its zonular fibres and more posteriorly by the ciliary body,
retina and optic disc. Its volume is about 4 ml, although this may
be as much as 10 ml in highly myopic eyes. Normally the space
is entirely occupied by vitreous gel a virtually acellular, viscous
fluid with 99 per cent water content. Its low molecular and
cellular content is essential for maintaining transparency. Major
constituents of the vitreous gel are hyaluronic acid and type 2
collagen fibrils . The cortical part of the vitreous gel has more
hyaluronic acid and collagen than the less dense central gel. In
addition, the gel exhibits 'condensations' both within its
substance and along its boundaries. Boundary condensations are
the anterior and posterior hyaloid membranes. The gel is
unimportant in maintaining the shape or structure of the eye;
indeed, apart from its role in oculogenesis, the vitreous has no
well substantiated function . An eye devoid of gel is not harmed
apart from having an increased risk of nuclear cataract, (which is
thought to be due to increased partial pressure of oxygen (po 2 ) in
the posterior segment after vitrectomy). The vitreous gel is
implicated, however, in the pathogenesis of a variety of sight-
threatening conditions.
During early development the invaginated optic vesicle (optic
cup) contains the primary vitreous, a vascularized tissue
supplying the lens and retina, both of which are of ectodermal
origin. During the third month of gestation the primary vitreous
gradually loses its vascularity and is replaced by the secondary
vitreous which is derived from the anterior retina and ciliary
body. The principal remnants of the primary vitreous are
Cloquet's canal, a central tubular stucture that stretches
sinuously between the lens and the optic disc and some
epipapillary gliosis. In later life an exaggeration of the latter is
seen as Bergmeister's papilla and a Mittendorf's dot is a primary
vitreous remnant seen on the posterior lens capsule (see Ch. 17).
The most common and severe developmental anomaly of the
vitreous is persistent hyperplastic primary vitreous. This usually
presents in infancy as a microphthalmic squinting eye with
leukocoria. Pupil dilatation may demonstrate dragging of the
ciliary processes towards a central plaque of fibrovascular tissue;
this invades the lens posteriorly and ultimately causes complete
cataract and secondary angle closure glaucoma (see Ch. 8).

neuroepithelium

artefactual separation
of optic vesicle

Fig. 12.1 Light micrograph of a section through the eye of a 13-mm human fetus
showing primary and secondary vitreous with artefactual re-establishment of optic
vesicle (silver stain).
 ANATOMY AND EMBRYOLOGY OF THE VITREOUS 3

cataractous lens

persistent hyaloid
artery

Fig 12.2 The hyaloid artery may occasionally persist as a vascular channel between the central gel and optic disc (left), or as a glial
plaque on the posterior lens capsule (centre). The B scan (right) demonstrates a persistent hyaloid artery.

VITREOUS ATTACHMENTS TO SURROUNDING STRUCTURES

The posterior hyaloid membrane adheres to the internal limiting
membrane of the retina (the basement membrane of the Muller
cells consisting of type 4 collagen) by the insertion ofvitreous gel
fibrils. The potential space between the internal limiting
membrane and posterior hyaloid membrane is the plane at which
the gel cleaves from the retina in posterior vitreous detachment.
The vitreous adheres to surrounding structures at various
sites; these attachments are responsible for much vitreoretinal
pathology. The vitreous base is an annular zone of adhesion
3-4 mm wide straddling the ora serrata. The anterior border is
the insertion of the anterior hyaloid membrane. The posterior
border forms the anterior limit at which the gel and retina can
potentially separate and is surgically important being a common
site for retinal tears. Adhesion of the vitreous base to the retina
and pars plana is strong and difficult to break even with severe
trauma. Weiger's ligament is a circular zone of adhesion,
8-9 mm in diameter, between the gel and posterior lens capsule.
It is the junction between the anterior hyaloid membrane and
the expanded anterior opening of Cloquet's canal. The posterior
hyaloid membrane and the slightly expanded posterior limit of
Cloquet's canal meet around the margin of the optic disc to
produce another ring of adhesion. During posterior vitreous
detachment gliotic tissue is avulsed from the edge of the optic
nerve head to produce Weiss' ring, a sign of posterior vitreous
detachment. A circle of relatively increased adhesion to the
retina may be present parafoveally and is implicated in macular
hole formation.
Vitreoretinal adhesions are exaggerated in areas of lattice
degeneration. Oval or elongated areas of retina are thinned with
sclerotic vessels and degenerate overlying vitreous. The lesions
tend to be oriented circumferentially but may also be radial or
directed along postequatorial retinal veins. Lattice degeneration
is found in approximately 7 per cent of normal eyes and is
frequently associated with retinal tears. Some eyes have
abnormally strong vitreoretinal adhesions along retinal veins
(paravascular adhesions) which may also result in retinal tears.

Weiger's ligament vitreous base

ora serrata

cystic tufts

paravascular adhesion

Cloquet's canal
epipapillary gliosis

Fig. 12.3 Diagram of normal vitreoretinal anatomy showing the macroarchitectural

features of the gel and the important sites of vitreoretinal attachment.
6 VITREOUS AND VITREORETINAL DISORDERS
VITREOUS CHANGES
POSTERIOR VITREOUS DETACHMENT
Posterior vitreous detachment which occurs when the posterior
hyaloid and internal limiting membranes separate is the
commonest and most important pathological event affecting the
vitreous. It occurs in about 50 per cent of individuals aged
between 40 and 80 years and earlier in myopes. Most patients do
not have pathological sequelae but acute symptoms of floaters
and flashers are associated with a 10 per cent risk of developing
retrolental gel
lacuna
vitreous gel
a retinal tear, the cause of most retinal detachments. The great
majority of tears are associated with visible retinal pigment
epithelium (RPE) cells in the anterior vitreous having been
released through the tear (Shafer's sign). Tearing of retinal blood
vessels or neovascular complexes causes haemorrhaging into the
vitreous cavity. Posterior vitreous detachment is also implicated
in the pathogenesis of epiretinal membranes and macular holes.
Fig. 12.4 With ageing vitreous degenerates to cause syneresis
(condensation) and lacuna (cavity) formation and collapse. At slit-
lamp examination the detached posterior hyaloid membrane looks
like a wrinkled hanging curtain moving freely on eye movement. It
separates from the retina up to the posterior border of the vitreous
base (or the posterior aspect of any vitreoretinal adhesions).
Weiss' ring
Fig. 12.5 On posterior vitreous detachment epipapillary glial
tissue can become avulsed from the disc margin and is seen
ophthalmoscopically as a ring of tissue on the detached posterior
hyaloid interface situated in front of the optic disc (Weiss' ring).
The patient sees a circular or oval floater (depending on how it
tilts) or describes a 'cobweb' or 'spider' that moves with the eye.
Aggregations of collagen fibrils can also produce symptomatic
floaters. 'Lightening flashes' may be seen in the temporal
periphery, each typically lasting for a few seconds and induced by
eye movement, possibly because photoreceptors depolarize when
the vitreous base tugs on the retina; these flashes are often more
noticeable on the transition from light to dark.
 VITREOUS CHANGES 367

VITREOUS HAEMORRHAGE

Vitreous haemorrhage can reduce vtswn profoundly.
Haemorrhage may be in vitreous gel (intragel) or behind a
detached gel (retrohyaloid); haemorrhage in both situations
tends to be associated with posterior vitreous detachment.
Spontaneous vitreous haemorrhage is principally caused by
retinal tears, retinal vein occlusion or retinal neovascularization,
for example secondary to diabetic retinopathy. Other common
causes are posterior vitreous detachment without retinal tear
formation or retinal macroaneurysm. Haemorrhage elsewhere in
the eye often disperses into the vitreous cavity (e.g.
suprachoroidal blood from trauma, subretinal blood secondary
to choroidal neovascularization or blood under the internal
limiting membrane in Terson's syndrome).
The blood in the vitreous gel initially forms a localized clot
but subsequently disperses throughout the gel following
fibrinolysis. During haemolysis biconcave erythrocytes loose
haemoglobin to become spheroidal erythroclasts. Biodegraded
haemoglobin stains the gel ochre-yellow or orange. Erythroclast
clogging of the vitreous cortex produces an 'ochre membrane ' at
the posterior hyaloid face. The mechanisms by which vitreous
haemorrhage is spontaneously absorbed are not clear although
phagocytosis by macrophages, outflow through the trabecular
meshwork and syneretic disintegration of the gel play a part.
Erythroclasts in the trabecular meshwork can reduce outflow to
produce raised intraocular pressure and 'erythroclastic
glaucoma' (see Ch. 8). Rarely, vitreous haemorrhage causes
'synchysis scintillans', a localized form of cholesterolosis bulbi
characterized by cholesterol crystal accumulation in the vitreous
cavity. The crystals sediment inferiorly but shower through the
vitreous cavity with eye movement.

Fig. 12.6 A bulla of subhyaloid haemorrhage forces the posterior hyaloid face
forwards into the vitreous cavity.

- - -----1 retrogel
haemorrhage

Fig. 12.7 B scans show a retrogel haemorrhage

moving from side to side with right and left gaze.
There is complete vitreous detachment from the
optic disc.
VITREOUS AND VITREORETINAL DISORDERS

VITRITIS

Inflammatory cell infiltration of the vitreous is a feature of patients to obtain specimens for cellular diagnosis, microbial
posterior uveitis, bacterial, viral, yeast and fungal infections, and culture, removal of the vitreous scaffold and delivery of
intraocular lymphoma (see Ch. 1 0). Vitreous biopsy or therapeutic drugs.
vitrectomy has an increasing role in the management of these

optic disc

foci of Candida

Fig. 12.8 Candidaemia in patients taking broad-spectrum

antibiotics or with indwelling intravenous catheters or in
intravenous drug users (Candida can grow in the lemon juice that
may be used to dissolve heroin), carries a significant risk of
metastatic endophthalmitis which manifests as intravitreal white
puff-balls. Candida endophthalmitis, although more slowly
progressive than bacterial endophthalmitis, usually requires
vitrectomy to remove the infected gel, to administer intravitreal
medication and to restore vision. Vitreous puff-balls are seen in this
intravenous drug user with Candida endophthalmitis.

ASTEROID HYALOSIS

Asteroid hyalosis is a specific form of gel degeneration in which preclude ophthalmoscopy of the retina although they rarely
globules of calcium soaps aggregate on vitreous fibrils and move impair the patient's vision. They are not associated with any
with the gel on eye movement. When dense, asteroid bodies may systemic condition and their aetiology is unknown.

Fig. 12.9 Typical white glistening particles are

seen in the anterior gel of this patient. B
scanning shows the densely reflective echoes in a
collapsed gel.

AMYLOIDOSIS
Amyloidosis of the vitreous is a very rare condition usually
associated with the primary or familial (dominantly inherited)
forms of amyloidosis. Proteinaceous material, probably derived
from the retinal circulation, becomes deposited on the
Fig. 12.10 Slit-lamp photograph showing proteinaceous material coating the
retrolental vitreous fibrils.
RHEGMATOGENOUS RETINAL DETACHMENT
Strictly speaking, 'retinal detachment' is a misnomer. Rather
than the retina detaching from choroid the retinal
neuroepithelium separates from the RPE to re-establish the
original space between layers of the embryonic optic cup.
'Rhegmatogenous' retinal detachment is most commonly caused
by a 'break' or full-thickness discontinuity in the neuro-
epithelium allowing fluid from the vitreous cavity to enter the
subretinal space. Classically breaks are subdivided into 'tears'
due to dynamic vitreoretinal traction and 'holes' secondary to
localized retinal disintegration or atrophy.
Most retinal tears occur in association with posterior vitreous
detachment from the forces generated by 'dynamic vitreous
traction'. This is the transmission of rotational energy generated
by saccadic ocular movement to the vitreous. If the vitreous
remains attached to the retina this energy is uniformly dispersed
over the whole area of vitreoretinal contact. With posterior
vitreous detachment these forces accelerate the posterior gel and
cause excessive traction at focal points of vitreo-retinal adhesion.
The vitreous base remains anchored anteriorly; such gel
movement can result in U-shaped tears at the site of 'abnormal'
vitreoretinal adhesions. The tongue of retina which produces the
U has its base anteriorly and points posteriorly; vitreous first
separates posteriorly, tears the retina at the point of adhesion
VITREOUS CHANGES
collagenous framework of the gel bilaterally to produce a 'glass-
wool' opacification; associated cellular invasion is conspicuous by
its absence.
then extends the tear anteriorly back towards the vitreous base.
Vitreous adheres to the periphery of lattice lesions so that the
traction tears along the posterior border of the lesion and then
extends anteriorly around its edge. Multiple tiny flap breaks at
the posterior border of the vitreous base are associated
particularly with aphakia or pseudophakia. If the flap of the tear
is avulsed completely from the retina the piece of avulsed
neurosensory retina is seen attached to the posterior vitreous
membrane as an operculum and a round tear is produced.
Haemorrhage from rupture of a blood vessel that crosses a U tear
may produce a floater or shower of floaters.
Rhegmatogenous retinal detachment may also arise from
atrophic retinal holes without posterior vitreous detachment,
often in young myopic patients, or by dialysis at the ora serrata.
In both retinal detachment is of slow onset, often noticed only
coincidentally at routine examination or when the condition
becomes symptomatic with foveal detachment. Atrophic holes
are often equatorial and associated with lattice degeneration.
Retinal dialyses are ellipsoid separations of the retina at the ora
serrata, usually inferotemporally. They differ from U tears
because there is no posterior vitreous detachment and the gel is
attached to the posterior rather than the anterior margin of the
break.
70 VITREOUS AND VITREORETINAL DISORDERS

FORMATION OF RETINAL BREAKS

Cystic tuft Opercu lated break Flap tea r with

with avu lsion gel attached
of retina and gel anteriorly

Vitreous attached

Retinal dialysis

Posterior vitreous
detachment
Weiss's ri ng

Fig. 12.11 Diagram illustrating the concept of dynamic vitreoretinal traction after posterior vitreous detachment and how this generates a
flap-tear or an operculated tear. In contrast with a dialysis the vitreous remains attached and there is no posterior vitreous detachment.

Fig. 12.12 Lattice degeneration containing round holes is seen in the

equatorial retina.

Fig. 12.13 AU-shaped horse-shoe tear is seen surrounded by subretinal

fluid.
 RHEGMATOGENOUS RETINAL DETACHMENT

anterior edge
· of dialysis

Fig. 12.14 A peripheral retinal dialysis seen through the indirect

ophthalmoscope.

indirect lens

round breaks

Fig. 12.15 Atrophic round retinal breaks are seen with an attached vitreous gel. They are usually equatorial and often associated with
lattice degeneration. Recruitment of fluid with round hole detachment probably occurs by connection of the hole to vitreous lacunae; this
may cause a stepwise detachment with multiple demarcation lines in a chronic-looking retinal detachment (see Fig. 12 .24) . The vast
majority will not cause retinal detachment and prophylactic therapy is generally regarded as unnecessary.
VITREOUS AND VITREORETINAL DISORDERS

sclerosed vei ns

Fig. 12.16 Retinal breaks are seen in a patient with retinal

vasculitis in whom the vitreous has separated avulsing small discs
of retina that remain attached to the posterior vitreous surface as
opercula. Round retinal tears result.

new collagen in gel

Fig. 12.17 Slit-beam photograph of the anterior gel after a retinal break showing RPE cells in the
retrolental gel (the 'tobacco dust' or Shafer's sign). Retinal tears are usually associated with release of
RPE cells into the vitreous cavity and, when seen, suggest that a retinal break is present. This is of
particular value when assessing a patient following an acute posterior vitreous detachment. These cell:
transform into fibroblast-like cells in proliferative vitreoretinopathy.

t---+-+---1 U t ear
ru ptured
.f-,-t.,b,---:,....-j--,\--1 blood vessel

Fig. 12.18 Haemorrhage from a ruptured blood vessel crossingf

U tear may produce a 'tadpole' floater or shower of floaters . Showr
here is a U-shaped tear, with a bridging blood vessel, surrounded
by laser scars. These breaks may still bleed despite the laser
therapy.
 RHEGMAT

SUBRETINAL FLUID ACCUMULATION

Separation of the neuroepithelium from the RPE occurs at first
in the immediate vicinity of the break. Progressively more
subretinal fluid is recruited from the vitreous cavity (from the
retrohyaloid space or syneretic gel) increasing the area and
elevation of retinal separation. If the globe is completely
immobilized at an early stage the retina may reattach partially or
even completely. This implies that the movement of the eye
causes gel movement and dynamic vitreoretinal traction that
extends the retinal detachment. Gel movement induces fluid
currents in the retrohyaloid space which forcefully elevate the
neurosensory retina and gravity encourages spread of the
subretinal fluid.
Subretinal fluid accumulates more quickly when fluid is
recruited from the retrohyaloid space (e .g. through aU tear after
posterior vitreous detachment) than when the posterior vitreous
is still attached (e.g. atrophic holes and dialyses). In the latter,
recruitment of fluid from syneretic gel may be limited by the size
of adjacent lacunae in the gel. As a retinal detachment progresses
the patient notices an increasing field defect corresponding to the
detached area; central vision becomes distorted and lost as the
fovea detaches.

a b c d

D Attached retina D Detached retina [] Breaks

Fig. 12.19 Gravity causes subretinal fluid to spread in a pattern that can help the surgeon localize a retinal break. A tear between the 11
and 1 o'clock positions causes a retinal detachment which becomes total (a). Tears above the horizontal meridian (from 3 to 9 o'clock)
produce subtotal detachments. Fluid recruitment progresses downwards on the same side as the tear, at first producing a concave edge to
the detachment, and then upwards as a convex edge on the opposite side of the disc but to a level lower than that on the side of the tear
(b,c). Inferior subretinal fluid from a superior tear tends to separate partially into two bullae leaving a cleft or 'cleavage' of less elevated
retina in the 6 o'clock meridian (b,c). A break located below the horizontal meridian tends to accumulate fluid more slowly than superior
breaks (d) . The upper limits of the detachment form convex curved edges on each side, the higher edge indicating the side of the break.
Bullae are not seen with inferior breaks. Occasionally a small anterior and superior tear leaks fluid down the post-oral retina, producing an
inferior retinal detachment. Therefore, inferior retinal detachments can occur from both superior and inferior tears.

NATURAL HISTORY OF RHEGMATOGENOUS RETINAL DETACHMENT

If untreated most retinal detachments progress to total or near-
total detachment. Visual loss is profound and potential recovery
of vision after successful surgery reduces as the weeks go by.
Initially the retina is thickened and becomes less transparent; if
left detached for many months it becomes progressively atrophic.
In a longstanding subtotal retinal detachment a 'high-water
mark' or pigment demarcation line of retinal pigment hyperplasia
may appear which sometimes stops the detachment from
extending further. Multiple high-water marks indicate recurrent
extension of the detachment and are seen more often in slowly
evolving detachments with round holes or dialyses. Other signs of
longstanding detachment include retinal cysts (secondary
retinoschises) and peripheral neovascularization. The longer the
retina remains detached the higher the risk of proliferative
vitreoretinopathy.
Very rarely the retina reattaches spontaneously to leave
pigmented chorioretinal changes; invariably, however, surgery is
required to reattach the retina. After successful surgery the rods
recover their function surprisingly well and any visual field defect
disappears. When the fovea has been involved recovery of cone
function is good if the detachment is treated quickly (within 1
week of onset) but central vision may be permanently impaired
after prolonged foveal detachment.
 Fig. 12.20 Characteristic wrinkling of the retina from outer
retinal swelling (outer retinal shagreen) is seen after detachment.

Fig. 12.21 These two photographs demonstrate a bullous superior retinal detachment with movement of subretinal fluid that spares the
fovea as the eye rapidly looks up and down; the retinal detachment is 'macula on' and freely mobile with no retinal fibrotic changes.

Fig. 12.22 The fovea has been elevated by subretinal fluid in this
'macula off' inferior retinal detachment.
 RHEGMATOGENOUS RETINAL DETACHMENT

degenerating
outer nuclear
and shed ding
layer
of receptor
outer segments

macrophage in
subretinal flu id

rod and con e

outer segments L-=.===-===~-"- lo==========='"===_i

Fig. 12.23 A comparison of the histological appearance of normal and detached retina demonstrates shedding and sh ortening of rod
outer segments. Pigment-laden macrophages are seen in the subretinal space.
By courtesy of Professor J M arshall.

Fig. 12.24 The pigmented demarcation line along the superior edge with thin
strands of subretinal fibrosis and a rather atrophic appearance suggests that this
retinal detachment is chronic.

Fig. 12.25 Intraretinal cysts in this retinal detachment suggests that the retina
has been elevated for at least a year. ·
 RETINAL DISORDERS

lens retina attachment

to optic disc
posterior
vitreous f----,c+---t:-----71
detachment

Fig. 12.26 A B scan shows a posterior vitreous detachment and total retinal
detachment with the retinal attachment to the optic disc visible. The degree of
retinal fibrosis can be assessed by watching the retinal mobility on dynamic B scan.
The more fibrotic the retina the less retinal movement on ocular movement.

retinal hole

Fig. 12.27 This patient has a spontaneously

reattached retinal detachment temporal to the macula
associated with a round hole in an area of lattice.
Although the retina is flat it is atrophic and the
patient had a corresponding nasal field defect.

PROLIFERATIVE VITREORETINOPATHY

Some retinal detachments, especially those present for weeks or detachment. Occasionally the proliferation is predominantly
months, are complicated by proliferative vitreoretinopathy (PVR), sub retinal producing fibrous strands that elevate the retina like the
a cellular proliferation producing 'epiretinal membranes' that has guy ropes of a tent or even 'purse-string' the retina around the
important implications in determining surgical management and optic disc. The response can be classified as:
visual prognosis. PVR is variable: some eyes develop proliferation
Grade A-clumping of RPE cells and stiffening of the vitreous
quickly whereas others with chronic detachment remain free from
Grade B-partial-thickness folding of the inner retina
proliferation. Proliferative change appears to start with RPE cells
Grade C-full-thickness fixed folding of the retina,
being dispersed from retinal breaks into the vitreous particularly
commencing as localized star folds and progressing
after retinopexy or failed surgery. Metaplasia to myofibroblasts
to an open funnel detachment, then to a closed
occurs through the action of growth factors released during or
funnel in the final stages. Grade C proliferative
after retinal detachment. Types 1 and 3 collagen are laid down and
vitreoretinopathy can be further classified according
contract as a wound healing response. Whereas wound
to where the folding occurs as either anterior (A) or
contraction on a planar surface usefully closes a wound, wound
posterior (P) to the equator, and by the number of
contraction on the inside surface of the spherical eye tends to drag
clock-hours of retina involved ( 1- 12).
the neurosensory retina centripetally to worsen the retinal

Fig. 12.28 This tear is distorted by early proliferative vitreoretinopathy. The

tear will be splinted open by the fibrosis unless this is removed during surgery.
 RHEGMATOGENOUS RETINAL DETACHMENT

,.,....,.-L---t--""='--"i centre of fibrosis

full thickness
-F""=--"-,....--',.___--1 fo Ids

Fig. 12.29 This retina is wrinkled by preretinal fibrosis from proliferative

vitreoretinopathy and graded as CP2 (full-thickness folds posterior to the equator
extending for 2 clock-hours).

"!-- ---"---1 distorted

flaptear

stretched
fixed folds of periphera l
oedematous retina
retina

oedematous
posterior retina

Fig. 12.30 Fundus photographs from an eye with a total

retinal detachment and m assive preretinal proliferation. The
immobilized central retina is drawn into an open funnel-shaped
configuration while stretching of the peripheral retina distorts
and immobilizes the original flap-tear.

inner retinal bridge of

folding or -="'~~::__ _j epiretinal fibrous
striation ti ssue

degenerate
photoreceptors

Fig. 12.31 Histological appearance of a fixed retinal fold

showing striation of the retinal surface and maintenance of full-
thickness folding by surface proliferations bridging between the
retinal leaves.
By courtesy of Professor J Marshall.

Fig. 12.32 (Left) B-scan ultrasonography showing a rigid,
closed, posterior funnel retinal detachment attached to the optic
disc indicating CP12 proliferative vitreoretinopathy. (Right) A
macrophotograph shows the clinical correlation.
DIFFERENTIAL DIAGNOSIS OF RHEGMATOGENOUS RETINAL DETACHMENT
The majority of retinal detachments are rhegmatogenous, caused
by a break in the retinal neuroepithelium. 'Traction' detachments
reflect the effect of 'static' tractional forces from fibrotic tissue
directed either along the posterior hyaloid membrane or on the
retinal surface. A combined rhegmatogenous and traction
detachment can occur in PVR when abnormal epiretinal
proliferation and contraction complicate the initial
rhegmatogenous retinal detachment. Alternatively, in other
'combined' detachments, tangential traction from epiretinal
proliferation is the primary event with subsequent retinal break
formation, as frequently happens in proliferative diabetic
retinopathy. Two other broad groups of retinal detachment are
recognized in the absence of retinal breaks: 'solid' detachments
(for instance those due to choroidal malignant melanoma; see
Ch. 9) and 'serous' detachments (uveal effusion syndrome,
Harada's disease, central serous retinopathy, polypoidal
choroidal vasculopathy; see Chs 9, 10 and 16). Disturbances in
other coats of the eye may mimic retinal detachment; these
include scleral infolding (e.g. from hypotony), scleral swelling
(e.g. from posterior scleritis), choroidal detachment, RPE
detachment and retinoschisis.
'bare' pigment epithelium
tight 'tubular' f---.7~~~-~ 1 1 ...
folding of retina
optic disc CO---"'"'"--"""-""-'--'-~=-...J
RETINOSCHISIS
Retinoschisis is a splitting of the neuroretina into two layers. It is
classically divided into 'juvenile' and 'senile' varieties. Juvenile
retinoschisis is a rare X-linked recessive dystrophy affecting
young males (see Ch. 16) and must be considered when a boy
presents with an apparent retinal detachment. A common
presentation is vitreous haemorrhage, and central vision may be
impaired by associated foveal schisis. The retina is split between
the nerve fibre layer and ganglion cell layer.
Degenerative or 'senile' retinoschisis is usually bilateral, tends
to be located inferotemporally, and is frequently discovered
during routine examination of the peripheral fundus. The retina
is split in the outer plexiform layer. The outer leaf of the schisis
often has a grey translucency with a mottled pattern; the inner
leaf is diaphenous and is most easily identified by the blood
vessels on its surface. Outer leaf breaks tend to be large with
rolled edges, whereas inner leaf breaks are usually small and
round. Progression of schisis itself is exceptionally uncommon
but combined schisis and rhegmatogenous detachment may
occur.
 DIFFERENTIAL DIAGNOSIS OF RHEGMATOGENOUS RETIN

Fig. 12.33 A retinoschisis with large outer leaf breaks in the

temporal peripheral retina. Outer leaf breaks tend to be large with
rolled edges whereas inner leaf breaks are usually small and round
and best seen in the thin diaphenous retina by an oblique view
with indirect ophthalmoscopy, with a fundus lens or three-mirror
lens.

UVEAL EFFUSION SYNDROME

The uveal effusion syndrome (see Ch. 9) is an unusual condition,
often mistaken for either a rhegmatogenous detachment
complicated by choroidal detachment or a 'ring melanoma' of
the anterior choroid. It is characterized by choroidal detachment,
mottling of the overlying RPE (leopard spots) and serous retinal
detachment which exhibits marked 'shifting fluid' (movement of
subretinal fluid with gravity). PVR is not seen as there is no
retinal break. The aetiology appears to be an abnormality of
trans-scleral fluid outflow from the vitreous through an
abnormally thickened sclera in a normally sized eye or vortex
vein compression in a nanophthalmic eye. Spontaneous
resolution may occasionally occur over months; otherwise the
effusion responds to scleral thinning and decompression
procedures.

Fig. 12.34 This photograph shows the typical 'leopard spot' pigmentation seen with chronic uveal effusions. These spots mask the
background fluorescence on angiography. A B scan is necessary to look for scleral thickening and an A scan to measure axial length. Similar
changes can be seen.
 TREOUS AND VITREORETINAL DISORDERS

SPECIAL TYPES OF RHEGMATOGENOUS RETINAL DETACHMENT

Certain rhegmatogenous detachments pose special management related, for example, to posterior paravascular vitreoretinal
problems owing to the unusual size or location of their retinal adhesions or to radially oriented postequatorial lattice
breaks. While most breaks are located between the equator and degeneration. This is especially true of the dominantly inherited
the ora serrata, more posterior breaks are sometimes seen vitreoretinal anomaly, Stickler's syndrome.

Fig. 12.35 Stickler's syndrome is characterized by myopia,

paravascular pigmentary changes, dragging of major vessels at the
optic disc, 'veils' or condensations of cortical vitreous around large
lacunae or dehiscences in the gel and multiple posterior
vitreoretinal adhesions. Patients have a characteristic facies with a
flattened nasal bridge, a short mandible and long philtrum; other
associations are a high palate and arthralgia . The gene has been
localized to COLIIAl.

RHEGMATOGENOUS MACULAR HOLE DETACHMENT

Fig. 12.36 Breaks in the macula of emmetropic eyes do not

usually cause retinal detachment (e.g. age related macular holes).
In highly myopic eyes posterior breaks especially at the macula or
temporal to the optic disc, often associated with areas of
chorioretinal atrophy and posterior staphylomas, can cause retinal
detachment. A macular hole has caused the retina to detach in this
myopic eye with the subretinal fluid accumulating at the posterior
pole. The detachment usually remains localized at the posterior
pole but occasionally extends anteriorly if peripheral breaks are
also present.
 SPECIAL TYPES OF RHEGMATOGENOUS RETINAL DETACHMENT

GIANT TEARS

bare pigment epithelium

totally detached retina f---->.,.----- rol led-over posterior

U tear t:==:"'::::~::::::::::::=__ _j edge of tear

Fig. 12.37 Other breaks are noted for their size. Giant retinal
breaks are defined as extending for over goo of the retinal
circumference with a freely m obile posterior flap. They are located
immediately post-orally or, less frequently, equatorially. They are
caused by vitreous traction (the gel being attached to the anterior
margin of the break). The posterior flap moves independently of
the gel, essentially by gravity, and breaks may extend radially and
posteriorly, especially at their upper limit. Giant tears may extend
from goo to 360° and often have satellite U tears. Giant tears are
commonly associated with congenital myopia, Stickler's syndrome
and trauma and have a high risk of developing PVR.

TRAUMATIC RETINAL DETACHMENT

Many types of retinal break are found in traumatized eyes; they of traction or as a consequence of later induced posterior vitreous
may develop at the time of impact or penetration, subsequently detachment.
from incarceration of the retina or vitreous and the development

flap tear
detaching posterior
margin of 'bucket
handle ' tear

disinsertion
penetrating wound

Fig. 12.38 Composite fundus painting demonstrating some of the types of retinal break seen after trauma . With blunt trauma the
commonest break is an inferotemporal dialysis which, because of the slow onset of detachment, remains asymptomatic for months or years
after the trauma until the macula detaches. The free posterior edge of torn retina may also become detached. Severe blunt trauma can
produce commotio retinae which rarely can develop into a large ragged degenerative break. Occasionally an avulsion of the vitreous base is
seen which comprises of a strip of ciliary epithelium, ora serrata and immediately post-oral retina, into which the basal vitreous gel remains
inserted; this 'bucket handle' is most often found in the supranasal quadrant and hangs down in the vitreous cavity. Penetrating trauma can
tear the retina at the site of injury or incarcerate vitreous, retina and choroid which progressively scars to shorten the vitreous and retina
and produce further tears either at the incarceration site or, due to transvitreal traction, elsewhere.
 INTRAOCULAR FOREIGN BODIES
Penetration of the posterior segment by a high-energy foreign
body can result in severe vitreoretinal complications. To diagnose
a retained small foreign body, careful attention needs to be paid
to the history of the details and circumstances of the injury. The
eye is examined for evidence of p enetration such as an entry site,
damage to the iris (often most easily seen by retroillumination)
or, after mydriasis, to the lens as well as hypotony and blood or
pigment in the vitreous. Immediate posterior segment damage is
generally restricted to where the foreign body ultimately imp acts
or through-and-through perforation occurs.
In most hammer and chisel accidents (probably the
commonest cause of intraocular foreign body), high-velocity
ferrous material penetrates the cornea or limbal sclera, lens and
vitreous and impacts in the retina. Initially there may be local
tissue coagulation from the h ot foreign body and bleeding into
the cortical gel around the site of impaction and along the ' track'
of penetration through the gel. If the foreign body impacts
chorioretinal scarring u sually secures the retina around the
foreign body but a retinal break leading to retinal detachment
may develop if the foreign b ody ricochets off rather than impacts
in the retina . Subsequent fibroblast proliferation may occur at
the site of impaction (to encapsulate the foreign body or distort
the underlying and adjacent retina) or along the haemorrhagic
track (to for m a transgel traction band). Visual loss depends on
the site of impaction (macular, papillary or peripheral), media
opacity (cataract or vitreou s h aemorrh age) and retinal
detachment. '
Surgical removal of the foreign body is indicated to avoid
severe posterior segment complications su ch as vitritis and
endophthalmitis (infectious or toxic, e.g. acute chalcosis).
Siderosis results from the ocular absorption of retained toxic
ferrous material. Glaucoma and cataract appear several months
after the injury (see Ch. 8). Destruction of photoreceptors
produces characteristic ERG changes that are useful in assessing
the remaining visual potential.
Radio-opaque intraocular foreign bodies are best detected by
orbit CT scans, although plain radiography is also useful for
screening and, by taking views on up and down gaze, showing
whether or not the foreign b ody is retained in the eye.
Ultrasonography is useful for detecting radiolucent foreign
bodies although its main value is for assessing their vitreoretinal
complications. Foreign b odies give rise to high-amplitude
echoes, provided they are appropriately oriented to the sound
beam. It is less effective for detecting small metallic foreign
bodies, especially when they are emb edded in the ocular coats.
Magnetic resonance imaging is absolutely contraindicated as
ferromagnetic particles rotate or move in the magnetic field .
Fig. 12.39 This patient has evidence of an intraocular foreign
body with a corneal laceration (repaired with suture) (top left), iris
damage, cataract and a poor red reflex from vitreous haemorrhage
(top right) . In another patient the entry site lies over the ~clera at
the limbus (bottom left).
 INTRAOCULAR FOREIGN BODIES

haemorrhage metallic foreign

in cortical gel body lyi ng on
over impact site reti na

haemorrhage syneret ic gel

along track of !--~--'""'--~• '"'­ k~;;;:;;~~- 1 ove rlying
fore ign body foreign body

Fig. 12.40 Fundus photograph of another patient shows a foreign body impaction site with prepapillary haemorrhage in the cortical gel
and along the track of the foreign body (left). A lacuna of syneretic gel is seen overlying a large reactive foreign body on the retinal surface,
viewed some days after injury (right).

foreign body intraocular

embedded in fo reign body
posterior retina
(change in foreig n body
location on v#l~~¥1-- embedded in
looking up and the superior
down) retina
haemorrhage

\
Fig. 12.41 Radiological detection and localization of a foreign body by an 'eye mover' lateral film (left) and by computed tomography
(centre). In another eye B-mode ultrasongraphy shows a large intravitreal foreign body with surrounding haemorrhage or vitreous
inflammatory reaction (right) .

foreign body

light pipe vitreous cutter

Fig. 12.42 Metallic foreign bodies in the posterior segment are best removed by
vitrectomy. This shows the operative view at the time of surgical removal.
VITREORETINAL COMPLICATIONS OF CATARACT SURGERY
Cataract surgery is associated with retinal detachment, occurring
at a rate of 0.1 - 1 per cent of cases. Major risk factors are the
degree of myopia and capsular rupture or vitreoretinal
complications at the time of surgery. The phrase 'dropped
nucleus' has been used to describe dislocation of the lens nucleus
(or part of the nucleus) of a cataract into the vitreous cavity
Fig. 12.43 Extensive soft epinuclear lens material can be seen lying in the posterior pole at the time of its surgical removal. In another
patient a dislocated silicone plate lens is seen on the inferior retina following laser capsulotomy.
EXTRARETINAL NEOVASCULARIZATION
Vascularized epiretinal membrane formation in response to
retinal hypoxia and ischaemia may be complicated by vitreous
haemorrhage, vitreoretinal traction and retinal detachment.
Causes of extraretinal neovascularization include retinal vein
occlusion, haemoglobin SC disease and retinal vasculitis but the
most common is diabetic retinopathy. Ischaemic diabetic
retinopathy characteristically affects the mid-peripheral retina
outside the major temporal vascular arcades and nasal to the
optic disc (see Ch. 15). Neovascularization generally develops
near the junction of ischaemic and normal retina (frequently at
the optic disc and along the major vascular arcades). Abnormal
neovascular tissue arising from intraretinal venules grows out
through the inner limiting membrane and proliferates on the
during phaco-emulsification. The nucleus can be seen in the
inferior vitreous accompanied by fluffy white soft lens material.
Pars plana vitrectomy and removal of the nucleus material is
usually required within 1 week to avoid the development of
glaucoma, chronic uveitis or corneal decompensation.
retinal surface or within the most cortical part of the vitreous gel
as a vascularized epiretinal membrane (flat new vessels). New
vessels do not grow into the central gel except occasionally within
Cloquet's canal. The membranes incarcerate the gel on which
they proliferate producing vitreoretinal adhesions.
Fibroblasts within the vascularized membranes contract to
cause tangential traction that is consolidated by subsequent
collagen synthesis. Tangential traction is exerted along the retinal
surface. It initially causes folding of the inner retinal layers
(internal limiting membrane and nerve fibre layer) and may then
progress to full-thickness retinal folding and to traction retinal
detachment. Anteroposterior traction is exerted along the
incompletely detached hyaloid face between the vitreous base

and the point of vitreoretinal attachment. Contraction of
membranes combined with vitreous gel shrinkage pulls the retina
at these points of adhesion towards the centre of the eye. Without
a retinal hole, subretinal fluid does not accumulate and the
detached retina has a concave configuration. The vitreous
detachment is taut and stretches from vitreous base to the
neovascular membrane and between membranes. Areas of retinal
detachment are often multifocal and surround neovascular
membranes on the retinal arcades. Eventually the macula
detaches whilst the periphery remains flat. If a hole appears in
the fragile ischaemic retina subretinal fluid will accumulate; the
retinal detachment then becomes convex and may extend
anteriorly in a bullous fashion.
The vascularized membranes tend to become drawn forwards
from the retinal surface and proliferate on the detached posterior
vitreous cortex. Bleeding into the vitreous from neo-
vascularization usually occurs at the time of posterior vitreous
detachment or from vitreous traction on neovascular complexes.
Haemorrhage invades the gel or, more commonly, the
vitreous
haemorrhage
cataractous lens
blood fluid
level vitreopapillary
attachment
Fig. 12.44 B scans showing a fluid level from retrogel haemorrhage over the posterior pole (left) and an intragel 'ochre membrane'
(centre). A traction retinal detachment is seen in (right).
vitreous
epiretinal
membrane
Fig. 12.45 Light microscopy of a diabetic retina shows a fibrovascular epiretinal
membrane producing outer retinal folding.
By courtesy of Professor J Marshall.
EXTRARETINAL NEOVASCULARIZATION 38
retrohyaloid space, which is loculated by the vitreoretinal
adhesions, often covering the macula posterior to the hyaloid
face. Retrohyaloid haemorrhage tends to clear more quickly than
intragel haemorrhage. With a long-standing intragel haemorr-
hage lysed erythroclastic red cells in the cortical gel tend to settle
on the internal side of the detached vitreous producing an 'ochre
membrane', clearly seen on B scanning.
Although vitreous haemorrhage may clear spontaneously after
some months, pars plana vitrectomy is frequently required to
remove the haemorrhage and rehabilitate the patient. Surgery is
more urgent in young diabetics to prevent irreversible loss of
vision. Concurrent panretinal photocoagulation is applied to
prevent iris neovascularization as removing the gel facilitates the
access of angiogenic factors to the anterior segment. Dissection
of any of membranes is required if there is significant neo-
vascularization or retinal detachment; membranes must be
removed totally to prevent future reproliferation and
detachment.
~£3
-~[i'\ posterior hyaloid membrane
~0'~
t&~~ forward traction of retina
i~o'
~1.
-.F'>•'-':o.) _H
VITREOUS AND VITREORETINAL DISORDERS

posterior . - - - - -7'7""---.-----.,-----.=-'--------. ora serrata

hyaloid membrane
vitreous base
retrohyaloid space
~----;1-----J'J"""'~ incomplet ely
attached retina detached gel
(·J'"'~-+----1 retinal vessels

wide vitreoretinal focal vitreoretinal

1/r.~'¥-:1'-----! adhesion
adhesion r------"~~~.4::.\

Fig. 12.46 Macrophotograph of a hemisected diabetic globe

shows an incomplete posterior vitreous detachment adherent to the
optic disc and temporal parapapillary retina.

Fig. 12.47 (Left) This diabetic shows gross neovascularization, fibrosis and vitreoretinal traction along the temporal vascular arcades with
tractional retinal detachment of the posterior pole. (Right) Inactive fibrotic changes are seen along the temporal vascular arcades with some
tractional retinal detachment temporal to the macula.
 MACULAR VITREORETINAL PATHOLOGY

blot haemorrhages

Fig. 12.48 This is the appearance of a diabetic traction detachment before and after operation following vitrectomy, membrane dissection
and intravitreal injection of gas to flatten the retina. The acuity improved from HM to 20/80. A considerable amount of retinal ischaemia is
evident in the posterior pole; this will require further laser photocoagulation.

MACULAR VITREORETINAL PATHOLOGY

AGE-RELATED MACULAR HOLE

Age-related macular holes are due to a dehiscence of the
neuroretina at the fovea which occur in middle-aged or elderly
patients, more commonly in women. They are bilateral in 10 per
cent of patients, usually presenting within 18 months of each
other. Patients present with blurred vision, distortion or a
scotoma. A helpful diagnostic test is the Watzke-Allen sign which
is the perception of a break in a narrow beam of light projected
on the macula. The underlying pathology appears to be
tangential vitreofoveal traction before a posterior vitreous
detachment has occurred which either causes a split (dehiscence)
in the retina or avulsion the neuroretina.
Optical coherence tomography (OCT) is invaluable in
confirming the diagnosis and in planning treatment. Macular
holes can be closed by vitrectomy with insertion of a gas bubble
to tamponade the hole for approximately one week. During this
time the patient has to position themselfface downwards to allow
the bubble to float upwards and tamponade the hole.
Supplementary manoeuvres such as dissecting the internal
limiting membrane off the retina or applying autologous platelets
to the hole, have been tried to maximize the chance of closure.
Successful closure arrests progression to a stage 4 hole. About 70
per cent of patients improve by two lines or more of vision; many
patients develop nuclear cataractous changes 1- 2 years after
surgery.
VITREOUS AND VITREORETINAL DISORDERS

Stage 1A
Im pend ing hole

--.
- ~~

· - "~- ~· --
~

-. --<

Stage 1B
~ Occulthole

. (: -- -~~ ·-' .
~ -~ :: "
,,II
~ ' •,

Normal Lamel lar hole

Stage 2
Hole

,. , "-.~~~_,::·· ·~WR'~:: ·9\'1'

. ' .~

Stage 3
Hole
.---
·'"'-
~"
~=··· ~-'l)"·"<b·' ..
,.~

Stage 4
Hole

Fig. 12.49 Classification of macular holes. Stage lA is an intrafoveal cyst. A yellow spot is seen with no PVD on biomicroscopy although
there may be perifoveal detachment on OCT. Sometimes the anterior lamellae may separate at the stage lA creating a lamellar hole. Stage
lB is an intrafoveal cyst with a posterior lamellar split. A yellow ring is seen on biomicroscopy with perifoveal detachment on OCT. The
patient is usually asymptomatic or may have some metamorphopsia. Stage lA and lB may resolve spontaneously with posterior hyaloid
separation or may progress to a full thickness hole with visual symptoms in 50% of cases, initially as a small hole of less than 300 ~-tm with
posterior hyaloid attached to the lip (stage 2), enlarging to a hole of more than 300 ~-tm diameter, the vitreous separated from the fovea but
with the PVD still incomplete (stage 3) and finally to a hole with complete posterior vitreous detachment (stage 4) over a few months.
By courtesy of Mr G Duguid.

Fig. 12.50 This fundus photograph shows a stage lB hole. OCT shows that the neuroretina has been elevated by vitreous traction. Many
stage 1 holes resolve or remain static.
 MACULAR VITREORETINAL PATHOLOGY

Fig. 12.51 A small grade 2 macular hole (left) and an OCT scan showing foveal dehiscence with separation of the posterior hyaloid
membrane and a tiny operculum (right). Cystoid spaces are present in the edge of the hole .

Fig. 12.52 A larger grade 3 macular hole. The visual falls to about 20/200 or CF. Typically the retina surrounding the hole is thickened
and small yellowish excrescences can be seen on the exposed RPE. Fluoroscein angiography will show mild hyperfluorescence
corresponding to the hole. OCT shows a partial vitreous separation from the fovea, an operculum and a large hole with rolled everted
edges, adjacent cystoid intraretinal spaces and a shallow rim of subretinal fluid.

full thickness
macular hole

Fig. 12.53 Histology of a stage 4 hole . Note the retinal pigment epithelium is intact.
VITREOUS AND VITREORETINAL DISORDERS
MACULAR EPIRETINAL MEMBRANE (PUCKER)
Idiopathic epiretinal membrane formation at the macula occurs
with posterior vitreous detachment producing the clinical entities
of macular pucker or cellophane maculopathy. In this situation
RPE and glial cells from the retina, migrating through breaks in
the internal limiting membrane, proliferate on the retinal surface
to produce traction on the retinal surface. Epiretinal membranes
can also occur without posterior vitreous detachment secondary
conditions such as retinal vein occlusion, retinal vasculitis,
cryotherapy or laser photocoagulation. The membrane can be
seen as a reflective sheet (cellophane maculopathy) with minimal
visual symptoms or as a thick opaque membrane drawing the
retinal vascular arcades together and sometimes giving the
appearance of a macular hole. The patient notices a reduction of
vision coming on over some weeks accompanied by distortion of
images and macropsia (increased image size) as the membrane
pulls the retina into the glial focus, often preceded by symptoms
of posterior vitreous detachment. After presentation, symptoms
and signs remain static in the great majority of patients. The
distorted vascular anatomy in the posterior pole gives the clue to
the diagnosis.
Fig. 12.54 The OCT shows an epiretinal membrane distorting
the inner retinal surface.
 MACULAR EPIRETINAL MEMBRANE (PUCKER)

disto rted
-~'----H vascul ar
pattern

Fig. 12.55 (Left) A fine epiretinal membrane is seen over this macula with vascular distortion and an appearance of a pseudo-macular
hole. Note the crinkly macular sheen from the epiretinal membrane giving the appearance of a pseudo-macular hole. Although the patient
had metamorphopsia the acuity remained good. On the right an epiretinal membrane can be seen distorting the blood vessels at
the posterior pole.

retinal
folds

Fig. 12.56 In this eye, retinal folds originate from an area of

epiretinal membrane temporal to the macula .
12 VITREOUS AND VITREORETINAL DISORDERS
Fig. 12.57 A gross epiretinal membrane can be seen in the left eye of this patient (right), distorting the retinal vasculature when
compared to the the normal eye (left).
PRINCIPLES OF VITREORETINAL SURGERY FOR RHEGMATOGENOUS RETINAL
DETACHMENT
A variety of surgical techniques are used to treat vitreoretinal
disorders; the choice of method depends on the condition
needing correction and on the individual surgeon's preferences.
Certain principles need to be followed, however.
RETINOPEXY
If a patient presents with a retinal break that is at high risk of
producing a retinal detachment (fresh U tear, paravascular tear,
operculated tear or dialysis) but has no subretinal fluid then
epiretinal
membrane
distorting retinal
vascu lature
retinopexy is applied to seal the tear and prevent fluid from
accumulating underneath the neurosensory retina. Laser therapy
around the break (usually in two rows around the circumference
of the break) or trans-scleral cryotherapy is used. Both methods
damage the neurosensory retina, RPE and perhaps Bruch's
membrane and choroid causing scarring that results in adhesion
within approximately 7 days sealing the retinal layers together,
preventing fluid accumulation and detachment. However, once
subretinal fluid is present, additional measures are needed to
relieve vitroretinal traction and produce contact between the
neural retina and RPE before retinopexy will work.
 PRINCIPLES OF VITREORETINAL SURGERY FOR RHEGMATOGENOUS RETINAL DETACHMENT 393

Fig. 12.58 Two rows of fresh argon laser burns seal this
operculated peripheral round hole; within days they will start to
become pigmented and atrophic producing a permanent
chorioretinal adhesion.

:::,_r .\
adhesive receptor outer
glial scar segments

pigment
u~~~~~~~~~~~~~~ epithelium

Fig. 12.59 The histological appearance of a chorioretinal scar induced by laser photocoagulation shows damage at the level of the RPE
and outer retina. Reparative glial tissue from the outer retina establishes a direct connection to Bruch's membrane. RPE cells have migrated
forwards in clumps.
By courtesy of Prof essor J Marshall.

REATTACHING THE RETINA, RELIEVING TRACTION AND TAMPONADE

Identifying and closing the retinal break or breaks is the prime
aim of surgery and is acheived either by an external approach or
byvitrectomy, depending on the case . Attaching a silastic explant
(aplomb) to the sclera indents the eye wall underneath the break
to relieve traction on the break and bring the retina and RPE into
contact allowing the retina to reattach. Alternatively, the vitreous
traction can be removed by pars plana vitrectomy and a long-
acting gas bubble, such as sulfahexafluoride (SF 6- lasts for 2
weeks and expands 2-fold) or carbon tetrafluoride (C 3 F 8- lasts
for 2 months and expands 4-fold) inserted into the vitreous
cavity. The gas bubble contacts the rim of the break (gas
tamponade) to prevent fluid re-entry through the break.
Thereafter subretinal fluid is reabsorbed and the retina flattens.
Retinopexy is always needed because the gas bubble is only
temporary and indentation from an explant gradually lessens
with time. Fibrosis and shortening of the retina from proliferative
vitreoretinopathy can prevent successful retinal reattachment;
hence the fibrous membranes need to be removed surgically and
in some cases the retina needs to be cut to relieve traction and
allow it to refit the inside of the eye (retinectomy) .
Perfluorocarbon liquids ('heavy' liquids) can be used during
surgery, for example to aid dissection of membranes, or to roll
out folded retina and giant tears or to elevate intraviteal foreign
bodies. When long-term tamponade is required silicone oil can
be injected into the vitreous cavity to keep the reattached retina
in place and allow time for the proliferative vitreoretinopathy
process to become quiescent. Long-term use of silicone oil in the
vitreous cavity is, however, associated with a number of
complications such as cataract, glaucoma, refractive changes and
low-grade retinal toxicity.
94 VITREOUS AND VITREORETINAL DISORDERS

Rectus muscle

Fig. 12.60 A large variety of shapes and sizes of episcleral

implants are available. This figure shows an encircling band, a
circumferentially placed tyre and a radial plomb.

lattice-based
breaks
ora serrata
cryo-adhesive scars

radial buckle from

L __ _ _ __ l_ _ _ _ _ _ ~
sponge
encircling buckle

Fig. 12.61 Fundus painting of total retinal detachment with multiple breaks in lattice degeneration shows how explants can be used and
the postoperative appearance after cryotherapy.

Fig. 12.62 Heightened light reflections are seen on the retinal

surface following intraocular silicone oil tamponade indicating
adequate oil filling.
PRINCIPLES OF VITREORETINAL SURGERY FOR RHEGMATOGENOUS RETINAL DETACHMENT 39

Fig. 12.63 Perfluorocarbon liquids ('heavy' liquids) have been

erroneously left in an eye after surgery and can be seen in the
anterior chamber resting on the inferior angle with a long-term risk
of glaucoma or corneal decompensation.
The Normal Retina,
Retinal Imaging and
the Interpretation of
Pathological ·
Changes
David Spalton, John Marshall, Victor Chong

The Normal Retina

Retinal Imaging
Physical Signs of Retinal Disease
398 THE NORMAL RETINA, RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

THE NORMAL RETINA

EMBRYOLOGY

The optic cup develops from the optic vesicle in the first 6- 7
weeks of gestation and consists of two layers of neuroectoderm
separated by a space. The outer layer of cells will eventually form
the retinal pigment epithelium (RPE) and the inner layer the
neurosensory retina; the potential space between them is re-
established pathologically in later life in conditions such as
rhegmatogenous retinal detachment or central serous
retinopathy.
The inner layer of neuroectoderm (i.e. that adjacent to the
vitreous gel) is initially about 10 cells deep. By 3 months of
gestation it has differentiated into two layers, the inner and outer
neuroblastic layers, separated by the transient layer of Chievitz.
During the next 2 months of development the inner neuroblastic
layer further differentiates: the presumptive ganglion cells appear
first and migrate towards the inner retinal surface where they
form the ganglion cell layer, the remaining cells migrate
downwards to form the amacrine cells of the adult inner nuclear
layer, the inner plexiform layer of nerve fibres and synapses forms
in between. Muller cells are differentiated early on from the inner
neuroblastic layer and then their nuclei migrate downwards to lie
in the inner nuclear layer. The outer neuroblastic layer also
contributes to the inner nuclear layer by supplying the horizontal
and bipolar cells, their migration obliterates Chievitz's layer. The
photoreceptors are the final layer to be differentiated although at
13 weeks the inner segments of the cones can be seen in the
macular area. Some authorities believe that the photoreceptors
are derived from the neuroectoderm of the outer neuroblastic
layer but it is more likely that they are adapted from ciliated cells
derived from the ependymal layer lining the primitive neural tube
and optic vesicle.
The overall adult arrangement of retinal layers is present by
51> months' gestation but retinal development is not uniform. For
example, although photoreceptors first differentiate at the
macula, this is soon overtaken by development in other retinal
areas so that at birth the macula is the only area not to be

primary vitreou s

signs of
formation of bl ood vessels
outer and inner of hya lo id
neuroblastic layers vascular system

Fig. 13.1 An axial section of the eye of a 20-mm fetus (6 weeks ' gestation)
shows the inner and outer layers of the optic cup; these will form the
neurosensory retina and RPE respectively. The primary vitreous and hyaloid
vascular system are visible, and the inner retina already shows signs of dividing
into the inner and outer neuroblastic layers.

o uter and inner

fusion of eyelids
neuroblastic layers

hyaloi d blood
formation of vessels
ganglio n cell layer
angl e of anterior
chamber

Fig. 13.2 An axial section of a 35-mm foetus (9- 10 weeks

gestation) shows that the eye is much larger and better developed.
The inner and outer neuroblastic layers are well formed .
developed fully- it is not completely developed until about 3- 4
months after birth, when the baby starts to fixate.
The RPE starts to become pigmented at about 6 weeks of
gestation and the process appears to be complete by 3 months
ANATOMY OF THE RETINA
The photoreceptors detect light and the RPE cells provide their
metabolic support. The inner retinal structure is supported by
the Muller cells. These are glial cells which support the neuro
retinal structure, they also have important metabolic functions.
The remaining neuroretinal tissue integrates and processes visual
information so that by the time the visual signal reaches the
axons in the optic nerve there has already been a considerable
processing of information.
The retina consists of just four layers of cells and two layers
of neuronal interconnections. In histological sections of the
retina, this simple six-layered structure appears lost and a far
more complex multistratified appearance is seen arising from the
D
ganglion cell layer
c
layer of intermediary
neurones
B } 5 ""Pro' """"' '""
photoreceptor
cell layer
A
retinal pigment {
epithelium
Fig. 13.3 The retinal cell layers are listed on the left and the apparent layers that these cells give rise to are shown on the right.
Bruch's membrane
Bruch's membrane is the basement membrane complex that lies
between the RPE and the choroid. In young healthy eyes the
retinal surface of Bruch's membrane is smooth and ensures the
regular alignment of RPE cells. By contrast, the choroidal surface
when the epithelium is seen as a densely pigmented monocellular
layer. Thus the RPE, derived from neuroectoderm, is fully
pigmented before the process of choroidal pigmentation, derived
from neural crest cells, has even begun.
juxtaposition of anatomically similar parts of adjacent cells. The
two so -c al~ed 'limiting membranes' are formed by components of
the Muller cells. Their nuclei are found in the inner nuclear layer,
and the cell extends across the retinal layers between the limiting
membranes. The outer limiting membrane, lying at the
innermost aspect of the inner segments of the photoreceptors, is
not a real membrane, but an alignment of junctional complexes
between adjacent Muller cells and photoreceptor cells. In
contrast, the inner limiting membrane on the retinal surface is a
tough acellular membrane, laid down by the Muller cells and into
which fibres from the hyaloid membrane of the vitreous cortex
insert.
II inner limiting membrane
I 0 nerve fibre layer
} 8 inner plexiform layer
} 7 '""" """~' '''"
} 6 outer plex iform layer
4 outer limiting membrane
3 inner segment
I retinal pigment epithelium
is irregular and projects columns into the intercapillary spaces of
the choriocapillaris. The structure of Bruch's membrane varies
topographically with the elastic layer relatively thin in the
macular region and much thicker in the periphery.

The retinal pigment epithelium
The RPE is a single layer of hexanocuboidal cells lying on
Bruch's membrane. The function of the RPE is to service and
maintain the overlying photoreceptor cells and in order to do this
it sustains five major processes. These are the absorption of stray
light, active transport of metabolites in and out of the
photoreceptor, the provision of a blood-retinal barrier,
regeneration of visual pigments and phagocytosis of the
photoreceptor outer segments.
The RPE cells contain fusiform granules of browny-black
melanin pigment in melanosomes which absorbs light strongly
between 400 and 800 nm and limits reflection or scattering
within the eye, thereby protecting the photoreceptor cells from
image degradation. With increasing age the melanin content of
the RPE cells decreases and many of the pigment granules are
degraded into phagosomes and melanolysomes.
In younger eyes the border of the RPE cell adjacent to
Bruch's membrane IS extremely convoluted and many
5 basement membrane of
choriocapillaris endothe lium
1 basement membrane of RPE
2 inner col la genous layer
3 elastic layer
4 outer col lagenous layer
5 basement membrane of
cho ri ocapillaris endothelium
endothelial cell
Fig. 13.4 Bruch's membrane is traditionally considered to have
five layers, which from retina to choroid are: (1) basement
membrane of the RPE; (2) inner collagenous layer; (3) elastic
layer; (4) outer collagenous layer; (5) basement membrane of the
choroidal capillaries, the choriocapillaris.
mitochondria reside within this portion of the cell. These
convolutions increase the surface area of the cell membrane
which is covered with specific biochemical binding sites. RPE
cells actively accumulate and transport metabolites diffusing
through Bruch's membrane from the underlying choriocapillaris
and actively excrete waste products to the choriocapillaris (the
retinal artery circulation does not contribute to the metabolic
needs of the photoreceptors). Each RPE cell services up to 45
photoreceptors held in close physiological contact by
membranous extensions from the surface of the RPE, termed
'receptor sheaths'. These sheaths extend up to 50 per cent of the
height of outer segments and play a major role in metabolite
exchange between the cells. The extracellular space between the
photoreceptors is filled with a glycosaminoglycans ground
substance called the interphotoreceptor matrix. This differs in
structure and chemical composition around rods and cones.
There is no anatomical bond between the RPE cell and
 THE NORMAL RETINA

photoreceptor so that these two layers can be easily separated
pathologically (e.g. by retinal detachment). However, the cone
matrix sheaths are more strongly adherent to the RPE and
resistant to the cone outer segment being withdrawn; this may
explain the increased resistance of the macula to retinal
detachment.
The action of light on the visual pigments in the outer
segments of the photoreceptor cells causes structural changes in
the visual pigment so that the chromophore separates from the
protein. In the rods this process is known as bleaching and results
in the visual pigment rhodopsin being split into retinol and the
protein opsin. The enzymes required for recombining the two
into rhodopsin are situated in the RPE. The RPE, therefore, has
a critical role in maintaining the visual cycle. Each RPE cell also
functions as a static macrophage in that throughout life it
phagocytoses the tips of the overlying rods and cones. The
engulfed particles, known as phagosomes, are progressively
degraded intracellularly by the action of lysosomes. The
breakdown products are then recycled to be incorporated into
the photoreceptor cells or voided from the RPE into the
choriocapillaris. With increasing age this system becomes less
efficient and breakdown products may accumulate in the RPE as
lipofuscin. The highest concentration of photoreceptors to RPE
cell occurs in the macula and throughout life the highest
concentration of lipofuscin is found here. Lipofuscin exhibits a
strong .autofluoresence and high levels are thought to be a risk
factor for age-related macular degeneration. The mechanism may
involve absorption of blue light resulting in RPE damage from
the generation of free radicals and apoptosis.

Fig. 13.5 A flat preparation shows the monolayer of hexagonal RPE cells and the natural colouration of their melanin granules. Tight
junctions or zonular occludens between RPE cells prevent free diffusion from the choriocapillaris into the neural retina. These junctional
complexes extend around the entire circumference of each RPE cell and bind it to its neighbours. The tight junctions and the active
transport mechanisms together constitute the 'outer blood-retinal barrier' which ensures that photoreceptor cells are exposed only to
selected molecules. The line drawing illustrates the intracellular anatomy. The complex of a pigment epithelial cell and its photoreceptors is
a highly metabolically active area and specific failures in the metabolic route to and from the photoreceptor produce many of the inherited
retinal dystrophies.

The photoreceptor cells

Although the photoreceptor cells are of two distinct types (rods
and cones), both show the same basic structural organization.
The cells are elongated and their cytoplasmic components
arranged in such a way that different functions take place at
specific positions along their length. The photoreceptor cell
transduces light to neuronal signals. The action of light on the
photoreceptor surprisingly results in the 'switching off' of the
cell. The sequence starts with photons being absorbed by visual
pigment m the outer segment that then undergoes
conformational change. The molecular changes in the visual
pigments cause the release of an internal transmitter from the
discs that passes in turn to the boundary membrane of the cell
inducing membrane alterations and hyperpolarization. The net
flow of current around the photoreceptor is changed and
switches off the release of neurotransmitter at the cell's synapse.
On returning to darkness the situation reverses and the
neurotransmitter is switched on again.
 IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

melanosomes

zonu lar
occl udens

phagosomes

Fig. 13.6 The zonular occluden s junction between RPE cells can be seen here. These surround
the cell en su ring that the m etabolites entering and leaving the retina from the choroid must pass
intracellularly.

Rod Con e can be thought of as analogous to a stack of coins in a tube. If

the tube is broken and the stack disturbed individual coins will
be lost. In cones the outer segments differ in that all the 'discs'
are joined to the boundary membrane with an aperture; through
this hole the discs are in contact with the extracellular space
and, therefore, with each other. Consequently, it is not possible
to isolate a single 'disc' from a cone outer segment.
Cone nucleus • A constricted region called the cilium which resembles the
structu re of other cilia in that it contains a number of paired
Inner segment microtubules.
Outer limiting • An inner segment which is the manufacturing portion of the
membrane cell; in each case this is divided into two, an outer ellipsoid and
an inner myoid. The ellipsoid contains mitochondria and
Ciliary rootlets provides energy for the transduction processes in the outer
segment, and the myoid contains Golgi bodies and ribosomes
for manufacture of cell components and membranes .
Basal body
of cilium
• An outer connecting fibre that runs from the inner segment to
the nucleus. In cones this tends to be short as the nuclei are
situated in the outer part of the outer nuclear layer close to the
outer limiting membrane . For rods the length varies with

r
Outer segment
Ciliary filaments
•
•
nuclear position.
A nucleus.
An inner connecting fibre that runs from the nucleus to the
synaptic region. In cones it is this structure that becomes

l
Pigment epithelium
• A synaptic region. In rods this is sometimes called the rod
Fig. 13.7 The structure of a photoreceptor consists of:
• An outer segment, which is the light-sensitive portion of the cell
and consists of a stack of hollow coin-like discs whose
membranes contain the visual pigment molecules. In each rod
there are about 1000 discs that are separate from all the others
and the boundary membrane of the cell. Rod outer segments
elongated as the fibres run out of the foveal pit to make contact
with the displaced intermediary neurones and form the fibre
layer of Henle.
spheral and in cones the cone pedicle. In both cells the synaptic
region contains vesicles and mediation of transsynaptic
inform ation is by chemical transmitters . Both cells exhibit so-
called invaginated connections with components from
intermediary neu rones deep to their synapse surface. These
invaginated synapses are called 'triads' because they contain
three processes, usually one from a bipolar cell and two from
horizontal cells. Rods have a single triad whereas cones may
have u p to 20.
 THE NORMAL RETINA

mitochondria
in ellipsoid

cilium

cone outer
segment

Fig. 13.8 Electron micrograph shows the junction between the inner and outer
segment of a rod. Note the cilium. Photoreceptor discs are formed by invagination of the
outer segment membrane. In contrast, cone outer segments remain attached to the cell
membrane over a small part of their circumference.

packages of
phagocytosed
rod outer
segments in
RPE cell

Fig. 13.9 Unlike neurones photoreceptor cells continually replace a major structural portion of
themselves throughout life and again this process differs between rods and cones. In rods new discs are
formed in the region of the cilium at the rate of about 1-5 an hour and as each new disc is formed
older ones are progressively displaced towards the RPE. The oldest discs are shed from the tips of the
outer segments in packets of about 30 at a time in a balanced process that does not radically alter rod
length. Packets of rod discs are shed first thing in the morning or, if in periods of prolonged darkness,
at the onset of light. The shed discs are phagocytosed by the RPE and, therefore, the rod outer segment
is replaced entirely every 8-14 days. Less is known about cones although the evidence suggests that
their discs are also renewed, however, the process is much slower than that for rods so that it takes
about 9 months to 1 year for the outer segment to be replaced fully. This time course is supported by
clinical observations on the recovery of cone function after retinal detachment surgery. In contrast to
rods, cones shed their phagosomes at night. This circadian rhythm is one of many thought to be
initiated by the effect of light absorption on the photopigment melanopsin which is located in some
retinal ganglion cells.
THE NORMAL RETINA, RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES
The inner retina
The inner nuclear layer contains the cell bodies of bipolar cells,
horizontal cells, amacrine cells and the Muller cells which are a
specialized glial cell. The bipolar cell was once thought to be the
only retinal neurone to connect the outer plexiform layer with the
inner plexiform layer thus effectively providing a channel for
information from the photoreceptor cells to the ganglion cells. In
reality, the bipolar cells do not connect photoreceptors directly to
ganglion cells because in the outer and inner plexiform layers
respectively the horizontal and amacrine cell processes intervene.
Thus, horizontal cells connect groups of photoreceptor cells
together and modify their group output through the triads in the
photoreceptor synapses before the signal is passed by the bipolar
cell to the inner plexiform layer. In the inner plexiform layer the
bipolar cells commonly synapse with amacrine cells which in turn
modify the signal before it is passed to ganglion cells.
Muller cells are specialized glial cells that form the scaffolding
of the retina. As they approach the vitreous cortex they expand to
form a large footplate which can sometimes be seen clinically in the
posterior pole as tiny reflecting spots known as Gunn's dots. Muller
cells produce the fibrous, acellular, inner limiting membrane, a true
membrane that is extremely strong. The outer limiting membrane
is not a true membrane but rather the close alignment of specialized
junctions of the Muller cells around the outer connecting fibres of
the photoreceptors. Apart from supporting the retinal structure
Muller cells are associated with nutrition of the photoreceptor
inner segments and the generation of neuronal impulses. They act
as an ionic reservoir during hyperpolarization of the photoreceptor
by light and this is reflected in their contribution to the b-wave of
the electroretinogram. They also proliferate to form the major
element of scar tissue or gliosis which is the retina's characteristic
response to cell death or disease.
The ganglion cell layer, together with its nerve fibre layer, is
the innermost layer of the retina. By the time the neuronal signal
Fig. 13.10 This illustrates the neuronal connections in the retina and the cells that
participate. Each neuronal cell eventually relates to a group of photoreceptors- its
'receptive field'.
is generated from these cells information has been coded to a
considerable extent. The retina responds to changes rather than
to a steady state so that changes in contrast or movement of
edges are important stimuli. Each neuronal cell in either the
inner nuclear layer or ganglion cell layer has its own receptive
field (i.e. an ultimate connection with a group ofphotoreceptors)
but receptive fields have been most studied at the ganglion cell
level. Foveal cones are said to have a 1 : 1 : 1 relationship with a
bipolar cell and ganglion cell, thereby producing a highly specific
pathway. Outside the fovea photoreceptors are grouped into
larger receptive fields. If taken on average, one ganglion cell
would service 130 photoreceptors, but, because the macular area
is served by over 50 per cent of the ganglion cells, receptive fields
in this area are far smaller than those in the periphery.
Some ganglion cells are turned off by a bright light projected
into the centre of their receptive field; others are turned on, in
effect giving a response to white on black or black on white.
Rods and cones can be integrated in receptive fields; some
receptive fields respond to a different colour or cone population
when stimulated centrally or peripherally. Some ganglion cells
give a sustained discharge if light is projected on to their
photoreceptors whereas others fire only transiently and still
others respond to a moving edge. There is good physiological
evidence to link midget ganglion cells to spatial discrimination
and visual acuity in the parvocellular pathway, whereas parasol
cells are concerned with detection of motion and direction in
the magnocellular pathway. Recently it has been shown that
some ganglion cells contain a light-sensitive pigment called
melanopsin with an absorption peak of 470nm. These cells are
thought to be an important element in the control of various
diurnal rhythms.
Topographical variation in the retina
Clinically the macula is the area within the temporal arcades
subserving the central zoo of visual field, the fovea is the
darkened area of light reflex and the foveola is the central pit with
a population exclusively of cones. The fovea is darker than the
surrounding retina, partly because of the presence of yellow
xanthophil pigment in the neural retina and partly because the
underlying RPE cells in this region are smaller and more densely
pigmented. The foveola contains only about Z500 cones, which
have long thin outer segments. Cones are found in greatest
density (15000/mm 2 ) in the fovea decreasing to about
4000- 5000/mm2 in the macula. In contrast, rods achieve their
greatest density at about zoofrom fixation (the field isopter just
peripheral to the optic disc). In total, the young adult retina
contains about 1ZO million rods and 6 million cones.
Fig. 13.11 In the foveola, the neural retina is about 170 mm
thick, compared to 350 mm in the fovea. This thinning arises
because the neurones of the inner retina, together with the
ganglion cells, are displaced radially as the nerve fibre layer of
Henle; incident light can thus fall on the highly specialized cones
without passing through a potentially light-scattering medium of
neural retina and retinal capillaries.
Fig. 13.12 At the fovea the cones have a tall slender shape with a
diameter of 1. 5 J.Lm permitting a resolving power of 20° of arc at
the nodal point of the eye.
 gang lion cells

inner nuclear layer

inner co nnecting
foveal cones f ibres of cones

Fig. 13.13 For the foveal cones to connect with the displaced inner retinal neurones, the inner connecting fibres of the cones become
very elongated and collectively form the fibre layer of Henle. Macular xanthophil pigment is located in this layer and absorbs blue light,
which is potentially harmful to the photoreceptors. Pathological oedema and exudation readily accumulate here because the inner
connecting fibres are not held tightly together. This is seen clinically as the radially oriented cystoid spaces of macular oedema or as a
macular star with lipid exudation.

160

140
M'
0
~ 120
"'
Cll
§ 100
v
0
"' 80
'0
e
....0 60
~

Cll
..c
E 40
:J
z
20

0
- Rods - Cones

Fig. 13.14 (Left) At post-mortem examination, the macula has a yellowish colour from the xanthophil pigment (hence the name macula
lutea). This pigment has a role in protecting the photoreceptors from short wavelength blue light which has the ability to produce cellular
damage as a result of the generation of free radicals. (Right) Histological examination shows the pigment in Henles layer.
Left image from Miller D (ed.) Clinical Light Damage to the Eye. New York: Springer, 1987.
 THE NORMAL RETINA

sparse inner
t hick ganglion non-pig mented ciliary
cel l layer at ganglion cells
neuroretina epith el ium
post erior pole at equatorial retina
I
.-~.·~ ;_;~::~~:.;;~;,~~~:;-;;-~;;;.;.;._;:,~_~,.~ - ~ RPE

~~=~:.:~==
~~
cystic spaces
outer pigmented
ciliary epithelium
ora serrata

Fig. 13.15 In the posterior pole the ganglion cell layer is several cells thick. Towards the periphery the retina becomes thinner and the
ganglion cell layer less dense. In the elderly the peripheral retina adjacent to the ora serrata may show cystic spaces within the attenuated
neuroretina . At the ora serrata the inner retinal layers are lost and the photoreceptors become shorter and fewer until finally the retina is
lost to fuse with the nonpigmented monolayer of the pars plana which runs forwards over the ciliary processes (see also Ch. 9) .

Retinal blood vessels

The central retinal artery supplies all the cells of the neural retina
with the exception of the photoreceptors which receive their
metabolic supply from the choroid by active transport through
the RPE (see Ch. 9) . The central retinal artery is a true artery
and as such can suffer atherosclerosis which may cause, for
example, a central retinal artery thrombosis. At the optic disc the
central retinal artery divides into four main branches which are
technically arterioles each of which is an end vessel with no
anastomosis. These arterioles have a media of smooth muscle 7-8
cells thick; they can undergo arteriolar sclerosis or hypertensive
changes but are not involved in atherosclerosis. The major
arterial branches run in the nerve fibre layer below the internal
limiting membrane and share a common adventitial sheath with
veins where they cross. Cilioretinal arteries are seen in about 20
per cent of patients and may be the major blood supply to the
macula in a minority of people.

ca pill ary-f ree

fovea

Fig. 13.16 There is a capillary-free zone around the retinal

arteries of 150 j.tm and within the foveola of about 400 jlm in
diameter. The foveola, the centre of fovea, is therefore
unencumbered by blood vessels which would otherwise degrade
visual acuity; like the rest of the photoreceptors this area receives
its blood supply from the choroid.

RETINAL IMAGING
A number of retinal imaging techniques are commonly used to
diagnose retinal diseases and to understand their pathogenesis.
Fluorescein angiography is a standard investigation. Indocyanine
green (ICG) angiography is particularly useful in situations
where fluorescein is 'masked' by haemorrhage or when the
choroidal circulation needs to be visualized. Optical coherence
tomography (OCT) is useful for assessing structural changes in
the macula and the vitreoretinal interface (see Chs 1 & 12) and
autofluorescence imaging can be used as a research technique to
study the lipofuscin load of the RPE.
FLUORESCEIN ANGIOGRAPHY
Over the past 30 years fluorescein angiography has greatly
advanced the ophthalmoscopic interpretation of retinal disease, so
much so that fluorescein angiography is now performed less
frequently for diagnostic purposes. Following an intravenous
injection of sodium fluorescein the dye is carried in the blood both
as the free molecule and bound to albumin. Dilute solutions
absorb light with a peak wavelength of 480 nm (blue) and emit it
with a peak wavelength of 530nm (yellow green). By using
appropriate filters exciting light can be separated from the emitted
light and this forms the basis of fluorescein angiography. Some
5 ml of 10- 20 per cent fluorescein solution is injected
intravenously through a butterfly cannula (severe anaphylactic
reactions can occur and, although rare, full resuscitation
Fig. 13.19 This photograph of normal rat retina (left), together with a freeze-dried preparation taken after the injection of fluorescein
(right), demonstrates that dye is kept intravascularly by the inner blood retinal barrier of the retinal circulation. Dye leaks from the
choriocapillaris into the choroidal extravascular space and spreads posteriorly to stain the sclera but is prevented from entering the retina
by the outer blood-retinal barrier of the RPE.
RETINAL IMAGING
equipment must be available). After 15- 20 seconds, the dye
appears in the eye and its transit through the choroidal and retinal
arteries to the veins is observed and imaged for later study.
The normal fluorescein angiogram demonstrates two distinct
circulations: retinal and choroidal. The choroidal circulation fills
a few -seconds before the retinal vasculature; choroidal blood flow
is high so that filling is completed rapidly. The choriocapillaris
has fenestrations at the junction between endothelial cells and
fluorescein readily diffuses out of these vessels to fill the
extravascular space. This lake of plasma is prevented from leaking
into the retina by the tight junctions of RPE cells (outer
blood- retinal barrier) whose pigment also tends to 'mask'
choroidal fluorescence. By contrast, in the retinal circulation
capillary endothelial cells lack fenestrations and have tight
junctions (inner blood-retinal barrier) so that fluorescein is
normally confined to the intravascular space. Hence, in the
normal angiogram the discrete retinal circulation is seen as
separate from the diffuse choroidal circulation because of the
RPE barrier.
Fluorescein angiography may be considered as a dynamic
study of the passage of dye from the arterial to the venous
systems in the two ocular circulations. As well as being able to
examine vascular anatomy and its variants, vascular pathology is
seen as changes in the dynamics of circulation or as signs of
breakdown of the inner or outer barriers. Points of particular
interest are delay or lack of filling of blood vessels and areas of
hypofluorescence or hyperfluorescence.
fluorescein dye
contained in retinal
vessels
" .
fluorescein dye
extravasated into
choroid
~-:._ . .
~- . · ~~~:::-_ . . . . ea rly sclera l stain ing
·- .
-
THE NORMAL RETINA. RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

Table 13.1 indicates the changes that can be seen on
fluorescein angiography. Hypofluorescence can be produced by
either a vascular filling defect in the circulation or blocking
(masking) of the normal retinal or choroidal fluorescent pattern
by, for example, blood or pigment. Hyperfluorescence may result
from leakage from retinal vessels (i.e. breakdown of the normal
inner blood-retinal barrier), atrophy of the RPE allowing the
choroidal fluorescence to be seen more prominently (window
defect), or breakdown of the RPE cell barrier (outer
blood-retinal barrier) in which case fluorescein is seen as pooling
and staining in the subretinal space. Neovascular tissue is
demonstrated dramatically by fluorescein angiography. All new
vessels, whether derived from the retinal or choroidal circulation,
lack tight capillary endothelial cell junctions and therefore leak
fluorescein; they fill in the early phases of angiography and leak
intensively as it progresses.

Table 13.1 Changes seen on fluorescein angiography

Hypofluorescence
Vascular filling defect
Masking of normal fluorescence,
e.g. by blood or pigment
Hyperfluorescence Angiographic features
Atrophy of RPE revealing choroidal _ _ _ _ _,.. Hyperfluorescence increases and decreases in
fluorescence 'window defect' phase w ith angiogram
Breakdown of outer blood-retinal barrier - - - - . . Slowly increasing hyperfluorescence throughout
angiography
Breakdown of inner blood-retinal barrier ---~ Leakage from retinal arteries, capillaries or veins
Neovascularization - - - - - - - - - - - - . . Early intense leakage, increasing in intensity and
area throughout angiography
Staining ---------------~ Retention of fluorescein from adjacent focal
leakage

The normal fluorescein angiogram

.---=-o::r--=c- - - - . patchy filling of

x:· \f':.--"""- 1 choriocapillaris
lobules

empty retinal veins

early retina I
artery filling
fil led cil ioretinal
'-----"""""--""""----'artery

Fig. 13.20 (Left) Colour images are taken before angiography for later comparison. A small cilioretinal artery can be seen on this optic
disc. (Right) In the earliest choroidal phase, there is patchy filling of the choriocapillaris due to its lobular supply and the deep optic disc
capillaries. As the cilioretinal artery derives from the posterior ciliary circulation it also fills in the choroidal phase. Dye is starting to appear
in the retinal arteries but the veins are empty and appear black against the background of the choroidal fluorescence .
 RETINAL IMAGING

masking of
choroidal
fluorescence
by macu lar --:~~::....J complete
pigment
/V1'dl~i!r'·/ 1 choroidal filling

Fig. 13.21 A second or two later choroidal filling is complete so that the retinal circulation is viewed against a uniform choroidal glow,
masked in the macular area by both the luteal pigment and the denser pigment in the RPE cells. Retinal arteries are well filled with dye.
(Right) The early arteriovenous phase shows complete choroidal and retinal arterial filling and laminar flow in the major retinal veins. This
is due to the presence of dye in the plasma adjacent to the vessel wall, the central blood stream being filled by a nonfluorescent core of red
blood cells.

scleral staining
of disc rim
fi xation pointer empty choroidal
bIood vesse I
seen against
background of
extravascular
fluorescence

Fig. 13.22 (Left) A later image shows complete filling of the various systems; laminar flow appears in the retinal arteries as they empty.
The vertical fixation pointer is easily seen against the background fluorescence and allows the fovea to be identified precisely. A late-phase
image (right) shows emptying of the retinal and choroidal circulations and some peripheral hyperfluorescence around the edge of the optic
disc from staining of the scleral rim . The fading choroidal fluorescence is masked in the macular ar-ea . Some of the larger choroidal vessels
are seen as filling defects in the choroidal vascular bed.

INDOCYANINE GREEN (ICG) ANGIOGRAPHY

Indocyanine green is a water-soluble dye that is highly bound (98
per cent) to albumin and lipoproteins. It absorbs red (790 and
805 nm) and fluoresces (835 nm) in the near-infrared range. This
allows more incident light to pass through the melanin of the
RPE and reach the choroid. The protein binding means that
more dye remains intravascular to show the choroidal vasculature
which allows better imaging of the choroid and associated
choroidal abnormalities, for example, focal leakage from
choroidal vessels in central serous chorioretinopathy or focal
accumulation of dye in choroidal vessels in idiopathic polypoidal
choriovasculopathy can be visualized. The fluorescence ofiCG in
the near-infrared range allows pathological conditions to be seen
through overlying haemorrhage, serous fluid, exudation and
pigment that would otherwise be blocked in fluorescein
angiography. Thus, occult choroidal neovascularization and
vascularized pigment epithelial detachment can be seen.
ICG is relatively safe but should not be used in patients who
are allergic to iodide or shellfish because ICG contains 5 per cent
iodide by weight. As the dye fluoresces in the near-infrared range
scanning laser ophthalmoscopy or infrared imaging systems are
needed to obtain good images. Although used for research
purposes the wider applicability of ICG angiography in clinical
ophthalmology is currently limited.
412 THE NORMAL RETINA, RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

Fig. 13.23 ICG using SLO imaging

of a normal eye. In the early phase
(left) there is filling of the retinal and
choroidal circulations with better
hypofluorescent definition of choroidal vessels
optic disc and
compared to FFA. In the late phase
retinal circulation
(right), the empty retinal circulation is
choroidal vessels seen against the uniform background
of choroidal fluorescence from
extravasated dye from the
choriocapillaris.
By courtesy of Mr Ethan Priel.

OPTICAL COHERENCE TOMOGRAPHY (OCT)

Optical coherence tomography (OCT) allows high-resolution
cross-sectional imaging of the retina in a way analogous to
ultrasonic B scanning (see Ch. 1) but with much higher spatial
resolution. It is a noncontact and noninvasive technique that is
particularly useful in imaging structural macular changes such as
measuring macular thickness, oedema and assessing
holes and vitreoretinal traction (see Ch. 12). It is less useful
identifying subretinal changes such as neovascularization.
development may have significant uses in measuring optic
cupping and nerve fibre layer thickness.

- - - - ---1 vitreous traction

on macula
Fig. 13.24 OCT image of the normal macular region;
(right) shows vitreoretinal traction to an early macular hole. optic disc
By courtesy of Mr P Stanga.
 PHYSICAL SIGNS OF RETINAL DISEASE

AUTOFLUORESCENCE IMAGING

Fundus autofluorescence originates in the RPE and has the by scanning laser ophthalmoscopy. Fundus autofluorescence
spectral characteristics of lipofuscin. With special processing and imaging is used in research to identify subtle changes in ageing
image enhancement autofluorescence may be reliably detected and hereditary macular dystrophies .

increased
autofluorescence

"A~"T"'---'ir---+--_J autofluorescence
from RPE

masking by luteal
and melanin
Fig. 13.25 The image of a normal eye (left) shows a darker area in the macular region
pigments due to the presence of macular pigment. In Best's disease (right), increased increased
hyperfluoresence is seen in the macular lesion.

PHYSICAL SIGNS OF RETINAL DISEASE

The retina can react only in limited ways to disease and exhibits appearances may be produced by a number of different disease
a limited range of physical signs so that similar fundus processes.

COTTON-WOOL SPOTS

Cotton-wool spots (sometimes incorrectly called soft exudates or
cytoid bodies) lie in the nerve fibre layer of the retina and
represent the ophthalmoscopic appearance of a microinfarct;
their presence implies ischaemic microvascular disease . The spots
appear initially as white fluffy patches, most commonly in the
posterior pole, as this is where the retinal nerve fibre layer is
thickest. They become smaller and more circumscribed with time
absorbing completely over 6- 8 weeks although they may persist
for longer in diabetic retinopathy. At this time a nerve fibre defect
may be seen as a groove in the retina corresponding to a bundle
of infarcted and destroyed axons and a matching tiny arcuate
field defect.
All neurones in the body transport intracellular organelles
bidirectionally between the nucleus and the synapse; this process
is known as axoplasmic transport. Pathologically, a cotton-wool
spot results from the accumulation of organelles as a result of
interrupted axoplasmic transport between the retinal ganglion
cell and its synapse in the lateral geniculate body (orthograde
transport), or vice versa (retrograde transport). Orthograde
transport is the more prominent component and largely involves
mitochondria. Electron microscopy and histological examination
show that the axonal stumps at the edges of a microinfarct are
packed with mitochondria which produce the white appearance.
(Papilloedema is produced by the identical mechanism of hold-
up of axoplasmic flow at the lamina cribrosa; see Ch. 17 .)
Cotton-wool spots are most commonly associated with diseases
that cause microvascular ischaemia such as hypertension,
diabetes, systemic lupus erythematosus and AIDS retinopathy.
THE NORMAL RETINA, RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

'--+-='l't-"1 hypofl uorescence

~~-=-~

Fig. 13.26 (Left) These fresh, fluffy cotton-wool spots are seen around the optic disc in a patient with recent-onset radiation retinopathy.
Their localization to the superficial retina can be seen by the way they overlay the retinal vessels. At this acute stage the nerve fibre layer
appears intact. Nerve fibre loss produces grooves in the nerve fibre layer; these take about 6 weeks to appear ophthalmoscopically. (Right)
The fluorescein angiogram shows that the cotton-wool spots correspond exactly to small areas of hypofluorescence in the retinal capillary
network. These persist throughout the angiogram and are not associated with extravascular leakage confirming their aetiology as
microvascular infarcts.

arteritic changes

fresh cotton- ~~:~N resolving cotton-

wool spot wool spot

Fig. 13.27 Photographs from a patient with an inflammatory

arteritis show a fluffy cotton-wool spot with some haemorrhage in
the acute stage (left). Note also the arteritic changes of focal
sheathing in the superior temporal artery. Six weeks' later (right),
the cotton-wool spot is absorbing and remains only as small, well
circumscribed spots. The arteritic changes are less prominent and a
nerve fibre defect has appeared.
 PHYSICAL SIGNS OF RETINAL DISEASE

frill of orthograde fresh, cloudy, sw ollen

axoplasmic hold-up and t otally infarct ed
from viable retina retina

Fig. 13.28 The distinction between retinal infarction and axonal infarction is shown by this patient with a recent lower temporal branch
artery occlusion. The retina supplied by the obstructed artery appears pale due to cloudy intracellular oedema of the infarcted neuroretinal
layers (which are supplied by the retinal circulation to the depth of the outer plexiform layer). A patch of viable retina remains in this
territory, however, supplied by a cilioretinal artery. These retinal ganglion cells are still able to generate orthograde axoplasmic flow which
passes along the axon until it reaches the area of ischaemia where it becomes held up as a thin, whiter frill of axoplasm corresponding to a
cotton-wool spot.

cytoid
bodies

stumps of retinal
axons distended
by axoplasmi c flow

ph otocoag ulation
--~"""":'~:--:"=
-l burns

Fig. 13.29 (Top) Light microscopy of a cotton-wool spot shows

the distended and disrupted axons in the nerve fibre layer.
Eosinophilic inclusions are seen in the axons and resemble a cell
nucleus, giving rise to the term 'cytoid body' . The true nature of
cytoid bodies as swollen axonal stumps is clearly demonstrated in
silver preparations. In this case (bottom right), the axons have been
damaged as they pass over an area of photocoagulated retina, and
the axonal stumps swollen with axoplasm can be clearly seen.
Electron microscopy (bottom left) demonstrates that these are
crammed with mitochondria and degenerating membranes.
16 THE NORMAL RETINA, RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

HARD EXUDATES

Hard exudates are formed by the deposition of lipid and
lipoproteins and are a sign of abnormal vascular permeability
from either optic disc, retinal or subretinal vessels. Lipid
deposition does not invariably follow vascular leakage: leakage is
an almost universal finding in posterior uveitis and yet hard
exudates are rare in this instance. Lipid is normally deposited at
the interface between normal and abnormal retina. Within the
retina a hard exudate is seen as a yellowish, well circumscribed
accumulation, deep to the retinal vessels in the outer plexiform
nerve fibre layer. They occur in two types of retinal distribution:
either as a circin~te pattern (a _complete or partial circk
separated from the leaking vessel by a clear zon~) or as a macular
sfar in which case the lipid accumulates in the fibre layer of
:HcrllPs surrounding the macula. Macular stars may result from a
leaking vascular focus either adjacent to the macula, in the
peripheral retina or in the underlying RPE. They m ay also result
from optic disc leakage when they tend to be more prominent on
the nasal side of the macula; these are particularly common in
the resolving phases of optic disc infarction. Further lipid
deposition in a circinate exudate or macular star will progress to
form a plaque of exudate.
Choroidal neovascularization with penetration of Bruch's
membrane is frequently associated with subretinal deposition of
lipid (see Ch. 16). Really gross examples of sub retinal lipid
deposition with serous detachment of the retina are seen with
Coats' disease and this can superficially resemble a
retinoblastoma (see Ch. 15).

circinate exudate

Fig. 13.30 In this patient circinate exudates are seen surrounding the macula. They have a circumscribed yellowish appearance deep to
the retinal vessels. In the macular area they adopt a more linear pattern from deposition within Henle's layer. Fluorescein angiography
demonstrates that the leakage originates from a previous macular branch vein occlusion.

Fig. 13.31 (Left) A photograph taken 2 weeks after argon laser treatment to the leaking area of retina shows that the exudates are
beginning to break up and absorb, especially inferiorly where the photocoagulation is heaviest. Occasionally following photocoagulation the
amount of hard exudate may transiently increase before starting to absorb. (Middle) The angiogram demonstrates scarring of the RPE
from the laser and less pronounced vascular leakage. (Right) Several months later the hard exudation has completely absorbed leaving RPE
scars in the affected areas.
 PHYSICAL SIGNS OF RETINAL DISEASE 41

pale swollen disc

circumpapillary nasal macular star

subretinal exudate

Fig. 13.32 A partial macular star and circumpapillary subretinal hard exudate is
seen in a patient with a pale, swollen and infarcted optic disc. Note the linear radial
deposition in the fibre layer of Henle's on the nasal side of the macula indicating the
optic disc to be the site of leakage.

Fig. 13.33 Histological appearance of hard exudates showing amorphous deposition of eosinophilic protein and lipid in the outer
plexiform layer. Muller cells probably limit the lateral spread of exudate.

RETINAL HAEMORRHAGES

Retinal haemorrhages are always of pathological significance.
Their ophthalmoscopic appearance indicates their anatomical
depth and this has implications for their aetiology and the clinical
sequelae. Haemorrhage may be found in the vitreous gel (intragel
haemorrhage), between the posterior hyaloid membrane or the
inner limiting membrane and the nerve fibre layer (preretinal,
subhyaloid or retrogel), within the nerve fibre layer (flame-
shaped haemorrhages), in the deeper retina (blot haemorrhages),
under the photoreceptors or under the RPE. All types of
haemorrhage mask the choroidal fluorescence on angiography.
THE NORMAL RETINA, RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

Posterior

cr--.:----:....-_-:_-_-_-_-: :_. - '.:-_.:· -.:~_-:=

....:. _--'.:_:.:._.:·:...:. . ... .:-s_:·.-"·.,·-~-~-~-~~~
~= :~,::~: ': :
\
'\.1----- Preretinal
haemorrhage

HHHf.··
Inner limiting
membrane

y y ~

I ~ (II ~ I II) II) I (II ~

I ' II ' ~ !f ' j ~~

Fig. 13.34 Preretinal haemorrhages result from bleeding into the subhyaloid space between the internal limiting membrane of the retina
and the posterior vitreous face. Sometimes a haemorrhage causes a localized detachment of the internal limiting membrane and then settles
with gravity forming a horizontal fluid level. The preretinal location is demonstrated by masking of the retinal blood vessels. Preretinal
haemorrhage is caused by bleeding from retinal tears, superficial retinal neovascularization or bleeding within the retina rupturing the
internal limiting membrane. With any persistent haemorrhage the haemoglobin can absorb from the erythrocytes to leave white
erythroclasts.

Fig. 13.35 Microscopy shows haemorrhage stripping the internal

limiting membrane of the retina.

nerve fibre haemorrhage

infarcted retina

Fig. 13.36 Nerve fibre layer haemorrhages tend to be seen in !!"le

posterior pole where the nerve fibre layer is at its thickest. They
havea linear, flame-shaped appearance caused by tracking along
the retinal axons and usually absorb with relatively little damage.
This patient also has areas of white retinal infarction from multiple
e~
 PHYSICAL SIGNS OF RETINAl DISEASE

blotchy haemorrhages
Fig. 13.37 (Blotchy haemorrhag~ lie deeper in the retina in the plexiform or inner
nuclear layer~e seen in the peripheral retina where the nerve fibres are thin . In these
regions the vertical arrangement of the Muller fibres and neurones limit lateral spre ad.-

capillary closure

bra nch ve in occ lusion

Fig. 13.38 Full-thickness retinal haemorrhage has a dark brownish, patchy appearance . This is usually a feature of venous occlusions or
diabetic retinopathy and is a sign of severe retinal ischaemia with retinal capillary closure indicating a high risk of subsequent retinal
neovascularization if this is extensive.
 extravasated
~=7::""~T"0m blood lying
extravasated diffusely in the
blood lying ganglion cell and
as globules nerve fibre layers
in the outer
retina l layers

= -- ·-~···-··-

Fig. 13.39 Dark brownish patchy haemorrhages are seen with full-thickness retinal haemorrhage. This is usually a feature of venous
occlusions or diabetic retinopathy and is a sign of severe retinal ischaemia with retinal capillary closure, indicating a high risk of subsequent
retinal neovascularization.

sub retinal haemorrhage w hite resolving

haemorrhage

Fig. 13.40 Subretinal haemorrhage appears as a blotchy red area (left) u~derlying the retinal blood vessels with the retina usually
elevated by the blood. In the macula these haemorrhages are frequently associated with choroidal subretinal neovascularization but, in the
absence of this, can als~ occur with trauma or excessive Valsalva manoeuvres. The density and extent of the haemorrhage can mask an
underlying neovas~ular membrane and, if treatment is to be considered, the patient must be observed until the haemorrhage clears
sufficiently to allow visualization of angio.graphic subretinal fluorescence which might take 2- 3 weeks or longer. (Right)~ subretinal
Il1!_emorrhage associated with a traumatic choroidal rupture. As the haemorrhage absorbs over a period of weeks, it can become -
depigmented with a whitish-yellow appearance as a result of the absorption of haemoglobin from the red blood cells leaving white
erythroclasts. .
 PHYSICAL SIGNS OF RETINAL DISEASE 42

preretinal haemorrhage

sub-RPE haemorrhag e

subretinal haemorrh age

Fig. 13.41 The RPE masks the redness of subpigment epithelial

haemorrhages which consequently appear dark greenish brown, as
in this patient with a bleed from a macroaneurysm. The
haemorrhage has burst through the RPE and retina to produce a
rim of subretinal haemorrhage and some preretinal haemorrhage.
Large subpigment epithelial haemorrhages can even be mistaken
for a malignant melanoma.

area of retinitis

Fig. 13.42 Roth's s ots are haemorrhages with a white centre that correspond to a cotton wool spot or a collection of polymorphs. Often
thought o.fas a manifestation of subacute bacterial endocarditis, they are a nonspecific sign tending to be seen more frequently in patients
with blood dyscrasias, anaemia or metastatic endophthalmitis.
MACULAR OEDEMA

The increase in retinal thickness and the unique structure of the peripheral retina. Macular oedema is a common feature of
nerve fibre layer of Henle result in the macula being particularly posterior segment mflammation, retinal ischaemia or retinal
susceptible to the accumulation of fluid and lipid from leaking vascular leakage with hard exudation.
vessels lying adjacent to the macula, in the optic disc or in the 1

optic disc and retinal

~-"lt--~--1 vessels partially
retina l folds obscured by vitreous
and debris
thickening

cystoid
macular
oedema

fluorescein
leakage from late phase
retinal cap illaries angiogram
and optic disc c<r:'~~--,-----1 showing
petaloi d cystoid
macular oedema

Fig. 13.43 Macular oedema is difficult to diagnose by direct ophthalmoscopy (left) and can be satisfactorily studied only with
biomicroscopy and a fundus lens (see Ch. 1). It occurs either as a diffuse thickening of the retina with a dull light reflex or, in more severe
cases, as cystoid oedema where cystic accumulations of fluid surround the macula in a petaloid appearance, as in this patient with posterior
uveitis. Early (middle) and late (right) phases of the fluorescein angiogram demonstrate dilatation and leakage from the veins and
capillaries of the retina and optic disc showing pooling of fluorescein in the extravascular tissue spaces corresponding to the cystic areas.
Macular oedema is u sually, but by no means always, associated with reduced visual acuity. It may persist for prolonged periods of time and
with resolution can leave a relatively normal macular appearance; alternatively coalescence of the cystic spaces can form a p artial thickness
hole or leave central RPE atrophy.
 PHYSICAL SIGNS OF RETINAL DISEASE

cystoid
spaces

inner nuclear layer

cystoid spaces
Muller cell core

photoreceptor nuclei

outer segments

cystoid spaces on OCT

Fig. 13.44 As the neural retina has limited intercellular space, fluid can accumulate only by physical movement of cells or their
components. In the outer retina oedema occurs predominantly in the nerve fibre layer of Henle but may extend between the outer limiting
membrane and the outer plexiform layer. The large spaces opened up in the retina show compression of retinal elements against the fibre
cores of the Muller cells; although the spaces appear to be individual cysts on angiography or histological examination they are, in fact,
interconnected as a single fluid-filled space.
424 THE NORMAL RETINA, RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

RETINAL PIGMENT EPITHELIAL DISTURBANCES

The RPE normally partially masks the background choroidal
fluorescence during angiography; therefore, increased
pigmentation will hide the choroidal fluorescence further
(causing a 'masking' or 'transmission' defect) whereas atrophy
allows the choroidal fluorescence to show more prominently
('window' defect). Atrophy of the RPE from any cause is often
accompanied b y adjacent areas of pigment hypertrophy.
Frequently RPE atrophy may not be very obvious
ophthalmoscopically but fluorescein angiography clearly
demonstrates the window defect. Increased fluorescence from
RPE atrophy appears and fades in phase as angiography
progresses. Large areas of atrophy often appear to have a
hyperfluorescent rim adjacent to the normal retina in the later
phases of performing the angiogram. This is due to fluorescein
leakage from the adjacent intact choriocapillaris diffusing
laterally to stain the sclera in the atrophic area .
Leakage of fluorescein through the RPE occurs as a result of
either functional breakdown of the RPE outer blood- retinal
barrier or choroidal neovascularization breaking through Bruch's
membrane and can be distinguished from a window defect by its
more intense fluorescence. With focal leakage angiography shows
early fluorescein leakage progressively increasing throughout the
angiogram to produce a hyperfluorescent pool in the subretinal
space. Neovascular tissue is distinguished from a disrupted
cellular barrier defect by its more intense leakage and increasing
area as the angiogram progresses.

Pigment
hypertrophy
blocking
r+-+-+-- transmission
of choroi dal
fluorescein

Fig. 13.45 Benign pigment epithelial hypertrophy is a common finding in Caucasian t;undi and is a good example of a lesion that masks
ch_groidal fluor.escence. T!_le flat, jes black lesion is avascular and well circumscribed. It results from hypertrophy of RPE cells which contain
more and large melanosomes and is totally benign and easily distinguished from a choroidal naevus or melanoma by its flat well-
circumscribed appearance. With time, the central pigmentation may atrophy leaving a depigmented ce~tre with surrounding pigmentation.

Fig. 13.46 RPE hypertrophy can take a variety of patterns collectively known as
' grouped pigmentation' or, more colloquially, as 'bear tracks' from their morphological
appearance. Such patients may have Gardner's syndrome (dominantly inherited intestinal
polyposis and bony osteomas with a very high risk of adenocarcinoma of the colon).
 PH YSICA[ SIGNS Of RE I IIlJA[ D ISEASE

Fig. 13.47 RPE hypertrophy must be distinguished from

~raretinal 12igmentatio which is always pathological and is
usually seen in various patterns as a sign of retinal dystrophy,
degeneration or inflammation. In the late stages of retinitis
J::>igmentosa, areas of black spidery 'bone corpuscular' pigmentation
are characteristi~a~lly seen in the retina, frequently adjacent to
blood vessels. RPE cells migrate into the neural retina and colonize
outside of the basement membrane of retinal capillaries.
Concomitant atrophy of the RPE is always present (see Ch. 16) .

window defect from

RPE atrophic changes

subretinal fibrosis masking of

fluorescence

Fig. 13.48 This eye has a macular scar, probably from toxoplasmosis, with areas of r-etinal pigment atrophy and hyperplasia. In addition,
there is white subretinal fibrosis, probably from previous subretinal neovascularization. Angiography shows the masking effect of the
pigmentation and associated window defects in the atrophic area. In addition the surrounding RPE has been damaged much more widely
than is apparent on ophthalmoloscopy.
 large
choroidal vessels

Fig. 13.49 RPE atrophy is almost invariably accompanied by loss of the choriocapillaris; extensive loss exposes the large choroidal
vessels.

focal area of
RPE changes

subretinal fluid
elevating macula

focal point
Fluid under of RPE increasing intensity
..,__ _ __ break and ----+- of leakage in late
r+--+-+-- photo-
receptors fluorescein stages of angiogram
leakage

Breakdown
" ..--1!1-lJ-..Ill--- of RPE Fig. 13.50 Mechanical breakdown of the outer blood retinal barrier of the RPE is
barrier
illustrated in thispatient with central serous retinopathy. A blister of subretinal fluid has
accumulated between the RPE and outer segments of the photoreceptors thus elevating
the macula. Angiography demonstrates a focal leak in the RPE through which this fluid
has been derived. Although this stains with increasing intensity as more fluorescein leaks
out during angiography, it lacks the early and sharply increasing intensity of neovascular
leakage .
 PHYSICAL SIGNS OF RETINAL DISEASE

.--h-1-/h+t'-t:H hyperf luo rescence

delineates RPE
detachm ent

Fluid
detaching Fig. 13.51 RPE detachments are not uncommon being seen either as isolated lesions
r+--+-+-+- RPE from (usually in young people), as part of the spectrum of age-related macular disease (see
Bruch's Ch. 16) or in some types of inflammatory disease such as the Vogt- Koyanagi- Harada
membrane
syndrome (see Ch. 10). They are due to the RPE separating from Bruch's membrane.
Their distinguishing angiographic feature is uniform hyperfluorescence that accumulates
during dye transit to delineate the area of RPE detachment. Bright hyperfluorescence or
uneveness of fluorescence suggests underlying choroidal neovascularization, which is an
important diagnostic feature for prognosis and management.

HH
Fig. 13.52 Scleral staining is seen in the late phases of
angiography around areas devoid of RPE and choriocapillaris,
such as a myopic crescent, of which this patient is an example.
The choriocapillaris in the healthy retina leaks fluorescein into
the sclera; this slowly spreads laterally to show as a
hyperfluorescent ring adjacent to the healthy retina .
28 THE NORMAL RETINA. RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

THE NEOVASCULAR RESPONSE

Neovascular tissue in the eye can be derived from the choroidal
or retinal circulations. (It can, of course, also be seen on the iris,
the angle of the anterior chamber and in the cornea.)
Neovascularization from retinal disease is associated with a wide
variety of diseases such as diabetes, venous occlusions,
retinopathy of prematurity or sickle cell disease. The common
factor across these widely varying conditions appears to be
retinal hypoxia which is manifested clinically by capillary closure
and loss of the retinal capillary bed. The precise events leading to
retinal capillary closure are still unknown . With branch venous
occlusion capillary closure usually occurs at the time of the initial
event although the areas of closure can extend or develop
subsequently.
There is evidence that retinal angiogenesis is controlled by the
release of a complex family of stimulatory and inhibitory growth
factors from hypoxic retina and, depending on the particular
circumstances, their release stimulates neovascularization on the
retina, optic disc or choroid. Biologically, ocular
neovascularization seems to be a similar process to wound
healing elsewhere in the body. The most important factor in
retinal neovascularization appears to be vascular endothelial
growth factor (VEGF) which targets mainly vascular endothelial
cells but can also act on RPE cells. Together with other growth
factors, VEGF induces a cascade of events to upregulate
transcription factors for matrix metalloproteinases that affect the
extracellular matrix, for mitogens that induce cell division, for
adhesion molecules that increase vascular permeability and for
the formation of tubular structures by endothelial cells. VEGF
diffusion through the vitreous gel and aqueous humour probably
results in neovascularization on the iris and the angle of the
anterior chamber. Although VEGF is important in the
development of choroidal neovascularization the process is more
complex. It is overexpressed in choroidal neovascular
membranes but overexpression itself does not in itself induce
choroidal neovascularization suggesting that additional factors
are implicated such as a stimulus caused by damage to Bruch's
membrane or a trigger from the RPE or choroid.
Neovascularization is always of great importance. Initially
retinal or optic disc neovascularization is usually seen as a flat
area of fine superficial blood vessels. Vitreous detachment is
induced at an early stage and drags the vessels forwards allowing
them to proliferate on the anterior hyaloid face (forward new
vessels). Within the eye all new blood vessels lack barrier
properties and rapidly and intensively leak fluorescein during
angiography which is a useful demonstration of their presence if
their clinical recognition is in doubt. New vessels are sight-
threatening because they are fragile and tend to bleed to obscure
the media. They are also associated with fibrosis and membrane
formation which leads to traction retinal detachment. Deposition
of hard exudates does not occur with retinal or optic disc
neovascularization but is a common feature of choroidal
neovascularization. The management of neovascularization in
retinal vein occlusions is discussed in Chapter 14, diabetes in
Chapter 15 and choroidal neovascularization in Chapter 16.

inferior t emporal capilla ry closure

vein occl usion

Fig. 13.53 Although iris neovascularization can occasionally occur with ocular tumours or posterior uveitis in the absence of capillary
closure, retinal capillary closure is almost always seen as a precursor of retinal neovascularization no matter what the primary cause may
be. In this patient with an inferior hemisphere vein occlusion, capillary closure can be inferred from the dark blotchy full-thickness retinal
haemorrhages. Fluorescein angiography shows massive capillary closure in the affected area.
 PHYSICAL SIGNS OF RETINAL DISEASE

perfused retina
retina l infarction

Fig. 13.54 This patient had an antiphospholipid antibody syndrome. He presented with rubeotic glaucoma in the right eye and sudden
visual loss in the left. Colour photography shows arterial and venous thrombosis with retinal infarction. Angiography shows that in the left
eye only a small area of peripapillary retina remains perfused. Such an eye has a grave risk of developing rapid iris as well as retinal and
optic disc neovascularization.

leakage of
fluorescein
from early
neovascu lar
complexes

Fig. 13.55 The optic disc is particularly prone to developing

neovascularization, possibly because it is itself an interface between
the retinal and choroidal circulations. Neovascularization is seen as
fine thready vessels that start to leak fluorescein early during
angiography and stain and leak intensively as the angiogram
progresses. This diabetic patient shows minute changes on the disc,
recognizable only on angiography.
JO THE NORMAL RETINA, RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

Forward proliferating
neovascu larization on
the posterior hyaloid

Optic disc

Posterior
vitreous detachment

Fig. 13.56 Neovascularization on the optic disc or retina induces

fluorescein partial vitreous detachment. New vessels are pulled forwards and
leakage are more vulnerable to minor trauma and haemorrhaging when the
gel moves and causes traction.

fibrotic tractional
retinal detachment

optic disc

Fig. 13.57 The end-result of untreated

optic disc neovascularization is visual loss
macula
from tractional retinal detachment and
vitreous haemorrhage.
 PHYSICAL SIGNS OF RETINAL DISEASE

neovascular tissue

perf used reti na

nonperfused retina
neovascula r 'sea fa n'
vascu lar shunts

Fig. 13.58 In the retina, neovascularization is usually seen at the boundary between perfused and nonperfused retina and is well
illustrated in this patient with sickle cell retinopathy. Note the vascular shunt.

13-11-1973 29-01-1974 30-04-1974 26-06-1974

vascular
remodelling
~~,_...J with areas of
ca pillary closure
c ____::__-"-- "-----'---___J retained

Fig. 13.59 Neovascularization can occur intraretinally, particularly in the area of venous occlusion or in areas of diabetic vascular closure.
This angiographic sequence shows the development of fine, stunted, intraretinal new vessels and vascular remodelling over a period of
several months following a branch retinal vein occlusion. These intraretinal new vessels, known as intraretinal microvascular anomalies
(IRMAs), are a common phenomenon adjacent to areas of retinal ischaemia but they remain stunted and do not grow progressively. They
do not cause any ocular morbidity or have the blinding sequelae of superficial neovascularization and can be thought of as an abortive
attempt at revascularizing the ischaemic retina.
Fig. 13.60 Choroidal neovascularization is most commonly seen as part of the spectrum of age-related macular disease in which it tends
to underlie the macula and destroys vision by causing haemorrhage, lipid exudation and subretinal fibrosis (see Ch. 16). Choroidal new
vessels fill with the choroid during early angiography and leak over time. This leakage is much more intense and brighter than that seen, for
example, with central serous retinopathy (see Fig. 13.47) or RPE detachment (see Fig. 13.48).

subretinal haemorrhage

w hite fibrotic tissue

Fig. 13.61 Subretinal fibrosis is seen as white tissue. It frequently ocurs as the end-result of choroidal neovascularization.

AGEING CHANGES IN THE RETINA

As part of the normal ageing process changes in the retina first
become apparent within the RPE as a build-up oflipofuscin. This
intracellular debris is thought to originate from the progressive
accumulation of partially degraded membranes phagocytosed
from the photoreceptor outer segments. This normal aging
process extends into the spectrum of age related macula
degeneration as the changes become more pronounced.
Following the accumulation of lipofuscin within the pigment
epithelium debris also begins to be deposited extracellularly
between the basement membrane of the RPE and the inner
 PHYSICAL SIGNS OF RETINAL DISEASE

collagenous layer of Bruch's membrane. This material within
Bruch's membrane may be diffuse when it is described as a 'basal
laminar deposit' or it may form localized accumulations called
drusen. As drusen increase in size they project through overlying
pigment epithelium towards the photoreceptor cells and further
compromise the already 'unhealthy' photoreceptors, leading to
further cell damage. In addition, Bruch's membrane thickens
with age restricting the passage of metabolites from the choroid
to the photoreceptor and the voiding into the choriocapillaris of
catabolites from photoreceptors degraded by the RPE. Age-
related macular degeneration is a spectrum of disease in which
both eyes tend to behave in a similar way, although there is
considerable interocular and interpatient variation. Drusen are
common in Caucasian eyes and are unusual in Blacks.

hard drusen

Bruch's membrane
choriocapillaris

~___:~__,""""'g.::=~k=.-J calcified
drusen

Fig. 13.62 Sub-RPE deposits. (Top left) Hard drusen lying between basement membrane of the RPE and the inner collagenous layer of
Bruch's membrane. (Top right) Soft drusen lying in a similar position; they are less homogenous and less sharply defined. (Bottom left)
Calcified drusen beneath a detached retina (Bottom right) Basement membrane deposit lying between RPE cell and its basement
membrane.
J34 THE NORMAL RETINA. RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

RPE
~---9---t----d:-r+---~- atrophy and
hypertrophy

Fig. 13.63 Drusen are commonly found in the macular area, but may be found anywhere in the posterior pole. The distribution in both
eyes is usually symmetrical. They are yellowish circumscribed areas of differing sizes, varying in appearance from fine granular deposits to
large, juicy confluent areas or hard, glistening calcific lesions (see Ch. 16). Drusen are distinguished from hard exudates by their deeper,
less defined appearance, their topographical location and bilaterality, and the absence of a concomitant retinal vascular focus of leakage.
During fluorescein angiography, drusen usually take up dye, which fades towards the later phases of the angiogram. If more intense leakage
occurs within a drusen, this may be a sign of early microscopic choroidal neovascularization (see Ch. 16).

atrophic RPE

calcified drusen

RPE hyperplasia

Fig. 13.64 Associated atrophy and hypertrophy of the RPE is

common with more pronounced disease.

RETINAL MEMBRANES

Epiretinal membrane formation on the retinal surface at the
vitreoretinal interface is associated with a wide variety of
disorders such as vascular occlusive retinopathy, excessive
photocoagulation or cryotherapy and posterior uveitis but many
patients who present with epiretinal membranes have no other
apparent ocular disease; in these cases age-related posterior
vitreous detachment is the underlying cause. The common
feature linking these diverse conditions is a physical disruption of
the internal limiting membrane allowing glial (Muller) cells to
spread from within the retina on to its surface; proliferation here
leads to traction and distortion. In the idiopathic variety, patients
usually present in their fifties and sixties with moderately blurred
vision and metamorphopsia. Once formed, epiretinal membranes
usually stabilize after about 6 months and do not progressively
cause more distortion and traction. By contrast, proliferative
vitreoretinopathy complicating rhegmatogenous retinal
detachment forms membranes consisting of RPE, glial cells and
fibroblasts that proliferate on both the anterior and posterior
surfaces of the retina to form collagen and causes progressive
contraction and traction. This may extend a retinal detachment
or if occurring after retinal detachment surgery, cause failure of
surgery (see Ch. 12).
 PHYSICAL SIGNS OF RETINAL DISEASE

wrin kled retina l

surface and
ep iretina l membrane

Fig. 13.65 Histological examination shows wrinkling of the

retinal surface by an epiretinal membrane .

Fig. 13.66 Cellophane maculopathy is the mildest form of epiretinal membrane formation and usually presents with slight blurring of
acuity and m etamorphopsia . Some epiretinal membranes will simulate macular oedema or a macular hole. In this patient, a preretinal
membrane lying inferior to the macula, which is clearly seen on red-free photography, mimics a pseudomacular h ole. It is not unusual to
find that traction and distortion of retinal vessels in the affected area cause vascular leakage and macular oedema. OCT can be very useful
in distinguishing the underlying pathology.

Fig. 13.67 This patient has a more marked membrane, reducing visual acuity to 20/60. Angiography shows distortion of the normal
vascular pattern.
436 THE NORMAL RETINA, RETINAL IMAGING AND THE INTERPRETATION OF PATHOLOGICAL CHANGES

epicentre

~?'7~~=___:,;~4-1 traction on the

macula

Fig. 13.68 This patient shows a more severe membrane with an epicentre on the
superior temporal vessels. There are prominent retinal folds, with traction and
distortion of the macula producing metamorphopsia. Such membranes are amenable
to removal by vitrectomy.

RETINAL AND CHOROIDAL FOLDS

Fig. 13.69 Retinal folds are seen

as fine striations of the retinal
surface. They do not alter the
fluorescein angiographic
appearance.

/~.;C·~,.z..--7'~---1 peaks and

troughsof
choroidal
folds
swollen d1

peri papilla
disciform

Fig. 13.70 In contrast, choroidal folds cause hypofluorescence and hyperfluorescent troughs on the angiogram as a result of folding of
the RPE .
The Retina: Vascular
Diseases I
David Spalton_, Jaheed !<.han_, John Shilling_, Victor Chong

Retinal Vascular Occlusions

Arterial Occlusions
Venous Occlusions
Slow Flow Retinopathy (Ocular lschaemic Syndrome)
Hyperviscosity Syndromes
Hypertensive Retinopathy
Retinal Macroaneurysms
Retinopathy of Prematurity
Traumatic Retinopathy
438 THE RETINA: VASCULAR DISEASES I

RETINAL VASCULAR OCCLUSIONS

The posterior ciliary circulation supplies the optic disc and
choroid through the short posterior ciliary arteries and the circle
of Zinn (see Ch. 17); the central retinal artery leaves the
ophthalmic artery in the orbit and only supplies the capillaries on
the surface of the optic disc and the retina (see Ch. 20) . Retinal
vascular occlusions are a common cause of visual loss especially
in elderly, hypertensive, diabetic or arteriosclerotic patients.
Patients usually present with sudden unilateral visual loss
although this might be noticed only coincidentally some time
after the initial event particularly in elderly people. All patients
need a careful assessment for associated underlying systemic
hypertension, diabetes or other atherogenic diseases. Subclinical
cardiac and cerebrovascular disease is frequently present and
patients should be investigated with these in mind as
prophylactic medical or surgical treatment might be indicated to
limit or prevent further systemic vascular damage.

ARTERIAL OCCLUSIONS

CENTRAL RETINAL ARTERY OCCLUSION

This is usually a disease of the elderly and is most commonly
caused either by thrombosis in the retrobulbar portion of the
central retinal artery or blockage of the artery by an embolus
which usually originates in the heart or carotid artery. Complete
occlusion may be preceded by attacks of amaurosis fugax. All
patients should be screened for hypertension, diabetes, cardiac
valvular and coronary artery disease and carotid atheromatous
disease. Temporal arteritis usually presents as an anterior
ischaemic optic neuropathy but occasionally causes a central
retinal artery occlusion (CRAO) and needs to be excluded (see
Ch. 17). In younger patients, the underlying aetiology is
occasionally found to be an inflammatory arteritis of which
polyarteritis nodosa, systemic lupus erythematosus and syphilis
are perhaps the commonest causes. Spasm of the central retinal
artery is an ill-defined and controversial phenomenon that
occurs only in exceptional circumstances such as drug toxicity
with ergot overdosage or pre-eclamptic toxaemia of pregnancy.
CRAO is a rare feature of migraine.
Experimentally retinal infarction takes 1 Yz hours of complete
arterial occlusion. Occasionally some eyes with CRAO achieve
some visual recovery probably because the embolus fragments
and disperses. If a patient is seen within a few hours of the initial
loss of vision it is worthwhile to presume that the occlusion is
embolic in nature. Working with this hypothesis attempts should
be made to dislodge the embolus by massaging the globe to
fluctuate intraocular pressure, giving intravenous acetazolamide
or performing paracentesis of the anterior chamber to lower
intraocular pressure. However, visual recovery is rare and the
prognosis is generally very poor. Patients have a reduced life
expectancy from vascular disease; cardiac infarction is the most
common cause of death.

cloudy swelling from

intracellular retinal oedema

cherry red spot

Fig. 14.1 The fundus of a recent CRAO shows a cloudy, opaque and swollen infarcted retina particularly noticeable in the posterior pole
where the retina is thickest. The fovea is the thinnest area of the posterior retina and there is little tissue here to infarct so that the underlying
redness of the choroid is seen contrasting with the whiteness ofthe surrounding infarcted retina to give the classical 'cherry red spot'
appearance. Within a few hours mild swelling of the optic disc often appears due to products of retrograde axoplasmic transport accumulating
in the optic nerve head. In the acute stage blood in the retinal arteries is dark from stagnation and the arteries themselves are often
attenuated. These acute appearances subside over a period of 2-4 weeks, usually leaving the eye with perception of light. Complete blindness
should suggest more extensive vascular occlusion involving the choroidal or optic disc circulation or ophthalmic artery.
 ARTERIAL OCCLUSIONS

Fig. 14.2 Fluorescein angiography is not usually performed but if

it is done: in the acute stages there is a considerable delay in filling of
the central retinal artery circulation following injection of dye; this is
seen as black retinal arteries against the normal background
choroidal fluorescence which, of course, is unaffected by the
occlusion. The artery fills eventually either directly or by retrograde
flow from the venous circulation. The central vessels in the posterior
pole fill poorly, possibly due to the retinal oedema increasing
external tissue pressure.

attenuated
arteries

lipid deposition

fig. 14.3 Late changes following CRAO in the right eye. The optic disc is pale and the branches of the central retinal artery are
anenuated in contrast to those of the normal left eye. Note the irregular whitish-yellowish deposition in the arterial walls which is probably
a mixture of gliosis and lipid deposition from vascular endothelial damage.

Fig. 14.4 Histology shows atrophy of the inner two-

thirds of the retina, (supplied by the retinal
circulation), following CRAO. The outer retina is
maintained by the choroid (see Ch. 13) .
0 THE RETINA: VASCULAR DISEASES I

Fig. 14.5 Cilioretinal arteries of varying size are found in about 20 per cent of eyes. These are part of the posterior ciliary circulation and
are therefore spared in a CRAO. The patch of retina supplied by the artery is left viable; if the patient is fortunate this will include the
macula . A small cilioretinal vessel is seen clearly in this patient supplying an area of retina temporal to the optic disc. Minute cholesterol
emboli can be seen in the inferior and superior temporal arteries and also in a small branch artery adjacent to the macula, indicating the
aetiology of the occlusion. Fluorescein angiography demonstrates the slow rate of filling of the retinal circulation and the normal filling of
the cilioretinal artery and choroid.

stagnated blood column

viab le retina

Fig. 14.6 This example of cilioretinal artery sparing in the presence of a CRAO in a
pigmented eye demonstrates clumping of the blood column in the inferior temporal
branch artery. This characteristic sign of a stagnant retinal circulation is known as 'cattle
trucking'.
 ARTERIAL

axoplasmic frill

Fig. 14.7 Cilioretinal infarction with central retinal artery sparing is the converse
situation to that shown in Fig. 14.5. Here, a small cilioretinal branch is occluded,
thus infarcting the retina temporal to the optic disc. A frill of axoplasmic material
from the viable retina is seen surrounding the cilioretinal infarct. Cilioretinal
infarcts have a similar aetiology to anterior ischaemic optic neuropathy, temporal
arteritis, which although it usually presents with more extensive disc infarction,
must be excluded as a potential cause.

RETINAL EMBOLI

Embolization of the retinal circulation usually occurs with
cholesterol or fibrin and platelet emboli from the carotid arteries,
or calcific fragments from a stenosed aortic valve. Occasionally
more exotic material such as talcum powder in drug addicts or
fat emboli in patients with multiple fractures can be seen. Emboli
may produce permanent or transient visual loss; cholesterol
emboli are also frequently seen coincidentally on routine
examination of an asymptomatic eye. Transient uniocular visual
loss is known as amaurosis fugax and is virtually always due to
embolization, whether or not emboli are actually seen on
examination. Patients typically notice uniocular visual loss
starting as a concentric peripheral dimming of vision or a vertical
curtain coming over the eye, depending on whether the central
retinal artery or a branch retinal artery is affected. Most attacks
last for periods of a few minutes but may persist for 2-3 hours
before vision quite rapidly returns to normal. Attacks may
happen singly or in groups, sometimes occurring in clusters or
showers during a day. Patients with retinal embolization have an
increased risk of developing a permanent stroke over the next few
months and the risk is substantially increased if the amaurosis
fugax is accompanied by signs of transient cerebral ischaemia or
an embolus is visible in the retina. This means that the
ophthalmologist plays an important role in the management of
these patients by referring them for prophylactic medical or
surgical treatment to forestall the development of permanent
neurological sequelae. In young patients, mitral valve prolapse or
cardiac septal defects can present as amaurosis fugax. Migraine
is another rare cause in young adults and m ay produce transient
visual loss by affecting either the retinal or the choroidal
circulation. The features are often atypical and more common
causes need to be excluded before a diagnosis is made. Choroidal
migraine produces patchy visual loss, rather like pieces missing
from a jigsaw puzzle, due to involvement of the choroidal lobular
circulation (see Ch. 9).

Fig. 14.8 Cholesterol crystals are seen frequently as a

coincidental finding in elderly patients and are a sign of
atheromatous disease in the carotid circulation (usually at the
bifurcation of the common carotid). They are flat crystals that glint
and reflect light as the ophthalmoscope is tilted to examine the
fundus and are most commonly found at bifurcations of the retinal
arteries. Because of the planar shape of the crystal, blood flow may
not be disturbed and the patient does not complain of any
symptoms. Cholesterol emboli are also known as 'Hollenhorst'
plaques after the Mayo Clinic ophthalmologist who made the first
description.
 Basilar artery

carotid artery

Right
subcl avia n art ery

Aortic
valve

Fig. 14.9 Cholesterol emboli usually arise at the bifurcation of

the common carotid artery, less frequently at the origin of the great
() Comm on sites of embolism
vessels. Calcific emboli usually arise from the aortic valve or
ascending aorta.

atheromatous cha nges

"!-- ---1 at bifurcation of
common carotid artery

Fig. 14.10 If the patient is likely to be a candidate for vascular surgery, imaging of the
carotid bifurcation is indicated to define an atheromatous lesion. This can be done by
Doppler ultrasonography or magnetic resonance angiography. These have now superseded
formal arterial angiography which carries a significant risk of stroke in its own right.
Clinical trials have established that if the patient is fit for surgery, symptomatic stenoses of
greater than 70 per cent are best treated by surgical carotid endarterectomy. Milder
degrees of stenosis and unfit patients are better treated medically with inhibitors of platelet
aggregation.
 ARTERIAL OCCLUSIONS

Fig. 14.11 Lipid deposition may be seen in the retinal arterial wall
following vascular endothelial cell damage after embolization. In this
patient there is marked yellowish white sheathing at the origin of the
superior temporal artery and, peripheral to this, the vessel is thin,
attenuated and fibrosed . Collateral vessels can be seen on the retina
and the optic disc has sectorial pallor; the patient had a dense inferior
nasal arcuate scotoma. Sometimes the lipid deposition occurs at a
bifurcation of a major retinal arteriole giving a 'trouser leg' pattern of
sheathing to the vessel.

embolus

infarcted retina

Fig. 14.12 Occlusion of a branch retinal artery is almost always the

result of embolization. In this patient with a branch inferior temporal
artery occlusion, a small embolus can be seen in the artery at a
bifurcation. The embolus is white and globular, unlike a cholesterol
embolus, and plugs the vessel. It originated from a stenotic aortic valve.

retinal infarction

Fig. 14.13 Platelet and fibrin emboli originate from an ulcerating

atheromatous plaque and look like soft porridgy material in the vessel.
They produce retinal infarction or amaurosis fugax and can sometimes
be observed moving slowly through the retinal arterial circulation as the
attack evolves. Video fluorescein angiography shows that transient
multiple platelet embolization is common during cardiac bypass
procedures.
THE RETINA: VASCULAR DISEASES I
VENOUS OCCLUSIONS
Retinal venous occlusions are the commonest retinopathy after
diabetes and age-related macular disease. They are classified
according to whether the occlusion affects the central retinal vein
or its tributaries. The early physical signs are dilatation of the
affected vein, haemorrhage in the territory of the retina drained
by the vein, retinal oedema, varying amounts of capillary closure
and retinal ischaemia with cotton-wool spots. Venous occlusions
vary considerably in their severity and the visual disability
depends on the part of the retina affected, the severity of the
occlusion and the amount of retinal ischaemia. Mild venous
occlusions cause visual disability from retinal haemorrhage or
vascular leakage and macular oedema whereas more severe
lesions also produce ischaemia and retinal capillary closure and
carry the risk of neovascularization.
CENTRAL RETINAL VEIN OCCLUSION
Mild central retinal vein occlusions (CRVOs) can be
asymptomatic but more severe occlusions present with loss of
vision due to macular oedema, ischaemia or haemorrhage, which
varies from minor to severe. Features of CRVO are retinal
haemorrhages which characteristically extend out to the
peripheral retina, dilated retinal veins, retinal oedema and
variable amounts of ischaemia. The appearance of the fundus can
vary from a grossly haemorrhagic fundus with optic disc oedema,
to mild forms with only a few fundal haemorrhages and mild
vascular changes; this range is reflected in the initial visual
symptoms and subsequent clinical sequelae.
Patients may present with nonischaemic or ischaemic
occlusions but about 30 per cent of patients presenting with a
nonischaemic CRVO progress to develop retinal ischaemia.
infarcted retina
Fig. 14.14 Embolization from fragments of a calcific aortic valve
are seen occasionally; their characteristic appearance is different
from that of other types of emboli, so aiding their identification.
They tend to be larger and globular with a pearly white appearance
and lodge in the larger arteries at the optic disc. Echocardiography
confirms the diagnosis.
Patients with the ischaemic type are more likely to have poor
presenting vision (worse than 20/200), a relative afferent
pupillary defect, cotton-wool spots, large areas of retinal
ischaemia and extensive deep haemorrhages in all four
quadrants. Significant ischaemia is defined on fluorescein
angiography as more than 10 disc diameters of nonperfusion.
Optic disc neovascularization is rare but ischaemic CRVO can
progress to neovascularization on the iris and in the angle and
eventually rubeotic glaucoma, typically about 3-4 months after
the acute episode. Panretinal photocoagulation can halt iris and
angle neovascularization and prevent rubeotic glaucoma. The
Central Vein Occlusion Study recommended waiting until new
vessels developed on the iris or angle before performing
panretinal photocoagulation but some retinal specialists believe
that early treatment with panretinal photocoagulation in eyes
with marked ischaemia is advisable, particularly when follow-
up may be difficult. Predictors of neovascularization include a
relative afferent papillary defect, vision worse than counting
fingers and more than 30 disc diameters of nonperfusion on
fluorescein angiography. Macular grid laser photocoagulation
has been shown to be ineffective for macular oedema in
patients with nonischaemic CRVO although some specialists
believe that young patients (aged less than 55 years) may
benefit from this treatment. No treatment has yet been shown
to improve the ocular prognosis.
Elderly patients with central retinal vein occlusion have an
increased incidence of arteriosclerosis, smoking, hypertension
and diabetes. The role of associated arterial disease in the
pathogenesis remains controversial but, as the central retinal
artery and vein share a common fascial sheath within the optic
nerve, thickening and hypertrophy of the artery can compromise
the vein's diameter leading to obstruction. Patients often notice
visual loss on waking with vision having been normal the night
before and it has been postulated that lower ocular perfusion
due to lower blood pressure and pulse rate and increased
intraocular pressure during sleep contribute to this (see Ch. 7).
CRVO is also a well recognized association of raised intraocular
pressure; this is particularly important to recognize as lowering
the lOP in the fellow eye may prevent a subsequent occlusion in
this eye.
Hyperviscosity states can produce a similar picture to central
vein occlusion from venous stasis, although a hyperviscosity
retinopathy is bilateral and usually less severe. Venous occlusion
must also be differentiated from low arterial pressure retinopathy
(ocular ischaemic syndrome or slow flow retinopathy).
Although CRVOs are most common in those aged over 60
years, younger patients may also be affected.
In younger patients an ocular or systemic vasculitis,
hyperlipidaemia and clotting abnormalities need to be excluded
in addition to the other risk factors such as contraceptive pill use.
CRVO can occur from inflammatory phlebitis in association with
sarcoidosis or Beh<;:et's disease. However, most younger patients
are generally well and have no associated systemic disease; the
probable aetiology in these patients is a congenital vascular
anomaly. In these patients involvement of the fellow eye, later
development of occult systemic disease or reduced life
expectancy from vascular disease is unusual.
Patients with retinal vein occlusion have an increased
incidence of death from cardiac or cerebral causes. Furthermore,
there is a 15 per cent risk of recurrence in the same or fellow eye
over 5 years. All patients require medical investigation
(Table 14.1).

Table 14.1 Investigation of patients with retinal vein occlusion

All patients More specialized tests as indicated
Full blood count and erythrocyte sedimentation rate (ESR) Plasma protein electrophoresis
Urea, creatinine, electrolytes, liver function tests Thrombophil ia screen, serum homocysteine
Fasting glucose level Antiphospholipid antibod ies
Fasting lipids Antinuclear antibodies (ANA), antineutrophil cytoplasmic antibody (ANCA)
Blood pressure (-reactive protein
Serum angiotensin-converting enzyme
Chest radiography
Electrocardiography
Thyroid function tests

Fig. 14.15 There is a wide range of spectrum appearances which reflect the degree of severity. These eyes show mild venous dilatation
and limited fundal haemorrhages. Fluorescein angiography shows venous and capillary leakage on the optic disc and in the retina. Retinal
haemorrhages mask the choroidal fluorescence.
 A: VASCULAR DISEASES I

Fig. 14.16 Patients with CRVO and macular oedema (left and centre) present with blurring of vision which tends to improve over 3-4
months as the central retinal vein recanalizes or venous collateral vessels develop on the optic disc to the choroidal circulation. At this stage
the visual acuity may improve and the retinal haemorrhages and macular oedema absorb. Six months later this patient shows a remarkable
improvement with improvement of acuity from 20/60 to 20/30. (right). In more severe cases the macular oedema may persist with
consequent visual loss.

cotton wool spots

Fig. 14.17 Signs suggestive of retinal ischaemia are dense, dark, blotchy haemorrh ages and cotton-wool spots. Retinal haemorrhages
make interpretation of the degree of ischaemia difficult in the acute stage as they mask the retinal capillary bed and angiography is more
informative if postponed until these have been absorbed. The major vessels fill with dye but there are large areas of capillary non perfusion.
In the later stages there is gross leakage of dye from th e major retinal vessels and the optic disc, especially in the ischaemic areas.
Surprisingly, marked capillary closure in the posterior pole can sometimes be compatible with reasonable preservation of visual acuity,
although the majority of such eyes have extremely poor vision.
 VENOUS OCCLUSIONS

gross ca pillary closure

Fig. 14.18 This eye shows gross retinal ischaemia and neovascularization on the optic disc.

iris neovascularization

Fig. 14.19 In the presence of gross capillary closure, 30-50 per cent of eyes develop rubeosis iridis and progress to thrombotic glaucoma.
Rubeosis iridis classically appears about 3 months after the vein occlusion. In the earliest stages a fine neovascular network is seen around
the pupil or the angle of the anterior chamber. This is followed by development of ectropion uveae from contraction of the neovascular
membrane, further vascular proliferation, glaucoma and corneal oedema (see Ch. 8). This sequence of events can be forestalled by early
panretinal photocoagulation as soon as the new vessels appear on the iris or angle; for this reason patients should be seen every month for 6
months after presentation. After treatment the rubeotic iris vessels will atrophy to leave the patient with an eye that has poor vision but is
comfortable. Retinal or optic disc neovascularization is very uncommon after CRVO. Glaucomatous eyes with rubeosis and visual potential
may be salvaged by a tube drainage procedure. Blind eyes can be made comfortable by topical steroid and mydriatic therapy but a
proportion of these eyes will eventually have to be enucleated as blind painful eyes.
THE RETINA: VASCULAR DISEASES I

swollen optic disc

blot haemorrhages

Fig. 14.20 CRVO may produce marked disc swelling that is distinguished from other causes of swollen optic discs by the presence of
haemorrhages in the peripheral retina in all four quadrants. Some of these patients may develop concomitant cilioretinal artery occlusion.
The perfusion pressure of the ciliary circulation is lower than that of the retinal circulation and the raised venous pressure increases the
retinal perfusion pressure above that of the ciliary circulation causing infarction. This patient presented with mild blurring of vision that
resolved, leaving a small centrocaecal scotoma.

Fig. 14.21 This eye shows collateral opticociliary shunt vessels on the optic disc as evidence of a previous resolved CRVO. These are
derived from normal vessels and shunt blood from the obstructed retinal venous circulation to the unobstructed choroidal circulation with
outflow through the vortex veins . The collateral vessels do not leak fluorescein, in contrast to neovascularization, because they are derived
from normal vascular channels with tight endothelial cell junctions.
 VENOUS OCCLUSIONS 44

Fig. 14.22 CRVO is common with glaucoma. The lOP and optic disc of
the fellow eye must be checked carefully in any patient with CRVO as this
may become the patient's only functioning eye. In many patients with
glaucoma the CRVO is subclinical, indicated only by the presence of shunt
vessels as a coincidental finding (see Ch. 7) .

Fig. 14.23 ·The optic nerve of a patient whose eye was

enucleated for thrombotic glaucoma shows gliosis and atrophy of
the nerve (compare with the normal nerve see Ch. 17). The
common fascial sheath of the central retinal artery and vein is
demonstrated; the artery is identified by its muscular wall. A
thrombus containing cholesterol crystals is lodged in the arterial
lumen, the.vein is pushed to one side, and there is recanalization
with multiple channels.

BRANCH RETINAL VEIN OCCLUSION

Occlusion of branch retinal veins produces a similar fundus
picture to that of central vein occlusion but limited to the
affected area. Most branch vein occlusions occur in the temporal
retina at arteriovenous crossings in patients with systemic
hypertension or arteriosclerosis. Thickening of the artery leads to
compression of the underlying vein within the shared fascial
sheath. Branch vein occlusions at other sites may occur from an
inflammatory phlebitis (see Ch. 10), with diabetes or
occasionally at the rim of a deeply cupped glaucomatous optic
disc where the vein bends over the rim.
Neovascularization can occur at the optic disc or peripheral
retina but rubeotic glaucoma is very rare after branch retinal vein
occlusion. Sectorial retinal photocoagulation is not indicated
unless there is retinal neovascularization; this carries a more
benign prognosis than other types of peripheral retinal
neovascularization and some retinal specialists wait until vitreous
haemorrhage occurs before embarking on photocoagulation.
Macular grid laser has been shown to be effective in treating
macular oedema due to leakage from branch vein occlusion.
However, the patient's vision commonly improves spontaneously
as the vein occlusion resolves and it is worthwhile delaying
treatment for 3 months and reserving treatment for patients with
vision of 20/40 or worse.
 E RETINA: VASCULAR DISEASES I

retinal haemorrhage
resolving haemorrhage
intraretinal leakage
of fluorescein

Fig. 14.24 A small macula branch vein occlusion is seen in a hypertensive patient who presented with blurred vision. Fluorescein
angiography shows the site of occlusion at an arteriovenous crossing with retinal vascular leakage, haemorrhage and oedema in the affected
area. Some weeks later the haemorrhage can be seen to be resolving with corresponding improvement in vision.

bifurcation of
central vein

Fig. 14.25 In some patients the central retinal vein divides within the disc and a major branch can be occluded within the disc,
producing a hemisphere venous occlusion analogous to a central vein occlusion.
 VEI'JOOS OCCLUSIONS

Sequelae of branch retinal vein occlusion

collateral venous shunts

intact capillary arcade broken macular

around macula arcade

Fig. 14.26 If the capillary vascular arcade surrounding the fovea is broken the prognosis for visual recovery is poor.

ve nous collaterals

Fig. 14.27 Following a branch vein occlusion collaterals may develop shunting venous drainage to the healthy circulation. These vessels
resemble venous collaterals on the optic disc in that they are derived from normal capillaries and do not leak fluorescein or produce ocular
morbidity.
2 THE RETINA: VASCULAR DISEASES I

--++~:+----'-'--'t----1 capil lary closure

/'/'~"h--'-,...---+-1 patent vein

Fig. 14.28 Major retinal arteries or veins that pass through an area of hypoxic retina may become white and sheathed with fibrosis and
lipid deposition in the vascular walls. These photographs show a superior temporal vein occlusion with dense dark haemorrhages and
cotton-wool spots indicating retinal ischaemia. The vein within the ischaemic retina has become white and sheathed. Angiography shows
considerable capillary closure but the vein is still patent. Such sheathing must be distinguished from the whiter, more ill-defined and fluffy
appearance of retinal periphlebitis (see Ch. 10).

in Hen le' s layer

Fig. 14.29 Visual loss in the acute stages of BRVO is due to involvement of the macula by haemorrhage, oedema or ischaemia. Vision
may improve as these changes resolve over weeks or months and if the capillary arcade surrounding the macula is left intact the visual
prognosis is comparatively good. Persistent visual loss may be caused by ischaemic macula damage, epiretinal membrane formation or
chronic macula oedema. Lipid exudation sometimes occurs some months after the initial occlusion and produces further deterioration of
visual acuity. This patient shows hard exudate and macula oedema extending into the viable inferior retina from a superior temporal BRVO.
Angiography demonstrates marked capillary dilatation and leakage in the area of the previous occlusion. If this area is photocoagulated, the
lipid will slowly be absorbed and further visual loss will be prevented.
Fig. 14.30 This patient has chronic macular oedema following a superior temporal vein occlusion. Following photocoagulation to the
affected area the oedema resolved as did the visual improvement.

Fig. 14.31 Severe branch vein occlusion with capillary closure may be followed by retinal neovascularization, usually at the junction of
ischaemic and healthy retina. There must be at least a quadrant of closure and commonly neovascularization takes about 6 months to
develop. These vessels readily regress following photocoagulation of the hypoxic retina. Rubeosis iridis is uncommon but when it does occur
it hardly ever progresses to thrombotic glaucoma. This patient shows a fibrovascular membrane with preretinal haemorrhage and traction
on the macula following an inferior branch retinal vein occlusion 6 months earlier. Angiography demonstrates the venous occlusion and
neovascularization in the scar and on the disc. Following vitrectomy, membrane peeling and photocoagulation, acuity remained unchanged
at counting fingers although distortion improved to some extent.
 SLOW FLOW RETINOPATHY (OCULAR ISCHAEMIC SYNDROME)
Poor arterial perfusion of the retina from severe occlusive
vascular disease (e.g. Takayasu's disease in young people, severe
carotid occlusion from atheroma in older people) produces a
fundus picture of dilated veins and peripheral haemorrhages,
similar to that seen in mild central retinal vein occlusion but
differentiated from this by a very low central retinal artery
perfusion pressure. Central retinal artery pressure must be
extremely low for these changes to occur; this low pressure can
readily be demonstrated by pulsation or occlusion of the artery
by slight digital pressure on the globe during ophthalmoscopy.
Patients may present with episodic blurring or washing out of
vision, sometimes precipitated by bright light, which can be
differentiated from amaurosis fugax because vision is not
completely lost. Severe hypoperfusion may lead to rubeosis
whic.h is difficult to manage . Carotid vessel surgery has not been
shown to improve visual outcome. The role of panretinal
photocoagulation in the prevention of glaucoma is controversial
and is possibly only effective in the presence of capillary closure.
peripheral blotchy
haemorrhage
Fig. 14.32 This 58-year-old man was a heavy cigarette smoker
with diabetes who presented with transient blurring of vision in the
right eye. Ophthalmoscopy showed mildly dilated retinal veins with
peripheral haemorrhages. The central retinal artery collapsed with
the slightest digital pressure on this globe.
". venous lea kage
peripheral
microaneurysms .- ~:~'~;,~:~:,~
Fig. 14.33 Fluorescein angiography showed prolonged slow
filling of both the choroidal and retinal circulations with diffuse
leakage from small vessels in the posterior pole and
microaneurysms and haemorrhages in the periphery in the later
phases. Magnetic resonance angiography showed that both
vertebral arteries and the right common carotid were completely
occluded. A Doppler study showed reversal of flow in the
ophthalmic artery, indicating that there was intracranial supply
from the external carotid artery.

HYPERVISCOSITY SYNDROMES
Blood viscosity can be raised by polycythaemia, increased levels
of plasma proteins from myeloma or exceptionally, by massive
leucocytosis in leukaemia. Waldenstrom's macroglobulinaemia is
the most common cause of hyperviscosity. It is a myeloma in
which large quantities of monoclonal lgM (the largest molecule
of all plasma proteins) are produced. Patients also have weight
loss, malaise, hepatosplenomegaly, Raynaud's phenomenon,
bleeding tendency and neurological signs. Although patients with
HYPERVISCOSITY SYNDROMES
hyperviscosity may develop a bilateral retinopathy of venous
dilatation and peripheral haemorrhages many patients have
normal fundi (apart from mild venous dilatation) in the presence
of very high plasma viscosity and the presence of a retinopathy
frequently correlates more with other concomitant
haematological changes such as anaemia and thrombocytopenia
rather than simple viscosity changes.
~-____,rl dark engorged
ret inal vein
coincidental
tilted optic disc
Fig. 14.34 This patient with primary polycythaemia rubra vera
shows dilatation of the retinal vessels with no other signs of retinal
ischaemia. The haemoglobin concentration was 23 g/1. The patient
complained of mild blurring of vision which improved rapidly
following venesection.
Fig. 14.35 This patient had the congenital cardiac defect of
Fallot's tetralogy. She has peripheral cyanosis, clubbing and
cyanosed retinal vessels.
56 THE RETINA: VASCULAR DISEASES I

Fig. 14.36 This patient had Waldenstrom's macroglobulinaemia with extremely high plasma viscosity, haemoglobin concentration of
8.9 g/1, and a platelet count of 120 000. The retinal veins are mildly engorged and peripheral haemorrhages are present.

Fig. 14.37 This patient with acute myeloid leukaemia presented with visual loss from macular haemorrhage, probably as a result of
anaemia and thrombocytopenia.
By courtesy of Dr E Graham.

Fig. 14.38 This patient with lipaemia retinalis had a familiallipoproteinase

deficiency with serum triglyceride levels of over 50 mmol/1.

HYPERTENSIVE RETINOPATHY
Systemic hypertension produces changes in the choroidal, retinal
and optic disc circulations; these changes depend on the severity,
rapidity of onset and duration of the hypertension and the age of
the patient. The branch retinal 'arteries' are, in fact, arterioles by
histological criteria. Recent work suggests that arteriolar
narrowing precedes the development of hypertension by
increasing the peripheral vascular resistance and haemodynamic
load. Narrowing of the arterioles reflects the intimal thickening
and medial hyperplasia, hyalinization and sclerosis seen
histopathologically. With accelerated hypertension necrosis of the
smooth muscle in the media from ischaemia, followed by
subsequent vascular dilatation and leakage of plasma into the
vessel wall produces fibrinoid necrosis. Occlusion, haemorrhage
and infarction follow.
HYPERTENSIVE RETINOPATHY 4!
The eye is the only site in the body where blood vessels can
be observed directly and several attempts have been made to
classify and grade the effect of hypertension on these vessels.
However, it is impossible to differentiate between the early
changes of hypertension and the normal ageing changes of
arteriolar sclerosis: changes in the light reflex of the arteriolar
wall and in arteriovenous crossing are seen in both and must be
interpreted in conjunction with the age of the patient. Arterial
attenuation, which may be focal or diffuse, occurs in both
situations. Severe systemic hypertension of sudden onset
produces a microvascular retinopathy with comparatively little
change in the major arterioles; the converse is true where the rise
in blood pressure has been gradual and prolonged allowing time
for compensatory sclerotic changes to take place in the major
retinal arteries.
irregular arterial
calibre
heightened
light reflex
Fig. 14.39 This photograph illustrates the fundus appearance of
a 40-year-old black patient with systemic hypertension of relatively
short duration. The inferior temporal artery has an irregular calibre
and increased light reflex from the vessel wall and there is
pronounced arteriovenous nipping where the vessels cross.
Although these changes are pathological in a young patient it
would be more difficult to say with certainty that they were so in
an elderly patient.
Fig. 14.40 Narrowed arterioles with focal attenuation can be
seen in the fundus of this 55-year-old seaman. The blood pressure
was normal indicating that these are arteriosclerotic rather than
hypertensive changes.
 TINA: VASCULAR DISEASES I

narrow
retina l lumens

in a cho roi dal arteriole

Fig. 14.41 In arteriolosclerosis (left) the smooth muscle of the vessel wall is replaced by collagen with narrowing of the lumen;
(right) shows fibrinoid necrosis in a choroidal arteriole .

Fig. 14.42 Retinal haemorrhages, particularly in the superficial retina

(flame-shaped) are a feature of chronic severe hypertension .
 HYPERTENSIVE RETINOPATHY

li pid exudate

cotton-wool spots
cotton-woo l spots

Fig. 14.43 Bilateral optic disc swelling or the sudden appearance of cotton-wool spots with hypertensive retinopathy is known as
accelerated hypertension. The prognosis is very poor if the blood pressure is not rapidly controlled to prevent cardiac failure and
hypertensive encephalopathy. This patient has acute hypertension of rapid onset and multiple cotton-wool spots in each eye . The main
retinal arteries are comparatively spared, indicating the acuteness and severity of the hypertension.

Fig. 14.44 This patient shows mild disc swelling in the left eye, cotton-wool spots, retinal haemorrhages and m acular stars, indicating
severe systemic hypertension. Macula stars suggest that the disc swelling has a vascular aetiology, commonly hyperten sive or ischaemic;
they usually appear as the disc swelling resolves.
 11 at RL IIICJA. VASCULAR DISEASES I

very atten uated

retin al arteries

disc swelling

lipid

Fig. 14.45 Swelling of the optic disc with accelerated hypertension probably results from local tissue ischaemia rather than raised
intracranial pressure, which is usually normal. Visual acuity remains normal in the absence of macula changes.

grossly swol len disc

Fig. 14.46 The blood pressure requires urgent control but this must be done cautiously as a sudden drop in tissue perfusion pressure car
cause infarction of the optic disc. This patient presented with blurred vision, a blood pressure of 210/ 130 mmHg and bilateral disc swelling
Over-enthusiastic control resulted in bilateral optic disc infarction and blindness of both eyes.
 Fig. 14.47 Changes in the choroidal vasculature with
hypertensive retinopathy do not usually affect vision but bullous
serous retinal detachments can be seen with very severe acute
systemic hypertension as a result of infarction of the
choriocapillaris and breakdown of the outer blood- retina barrier.
Elschnig's spots represent foci of infarction of the choriocapillaris
in the posterior pole with overlying changes in the retinal pig/nem
epithelium (see Ch. 9).

massive hard
~'fil----l exudate
with partial
macular star

Fig. 14.48 Hypertension with renal failure can produce a much more exudative pattern of retinopathy with less evidence of retinal
ischaemia. Following control of blood pressure and renal dialysis in this patient the retinal exudate was absorbed over several months and
visual acuity returned to normal.
2 THE RETINA: VASCULAR DISEASES I

RETINAl MACROANEURYSMS

Macroaneurysms of the retinal arterioles are usually seen in
elderly patients with systemic hypertension; they are similar in
pathology to the Charcot- Bouchard aneurysms of the cerebral
circulation which are thought to be due to embolization with
damage to the arterial wall. Retinal macroaneurysms tend to
occur at the branching points of second or third order arterioles.
They may be found either coincidentally or because they cause
visual disability due to haemorrhage or leakage of lipid and
macula oedema. Studies have shown that the haemorrhagic
complications resolve spontaneously and do not require specific
treatment but that exudative changes should be treated by
photocoagulation as they may damage the fovea producing
permanent visual loss. Retinal macroaneurysms must be
distinguished from Leber's miliary aneurysms (see Ch. 15) or
vascular anomalies due to venous occlusions or diabetes.

Fig. 14.49 This patient has a localized posterior vitreous separation and preretinal haemorrhage from a macroaneurysm. The
haemoglobin is being absorbed from the haemorrhage leaving white erythroclastic ghost cells. Macroaneurysms can often be difficult to
identify by ophthalmoscopy but are readily demonstrated by fluorescein angiography. The haemorrhage masks the background choroidal
fluorescence and the aneurysm is seen as a hyperfluorescent saccular dilatation of the artery- the 'light bulb' sign.
 subretinal lipid
Fig. 14.50 This patient has a macroaneurysm on the superior temporal artery with marked subretinal exudation. Fluorescein
angiography shows a hyperfluorescent aneurysm.
RETINOPATHY OF PREMATURITY
Screening for retinopathy of prematurity (ROP) has increased in
importance with the development of neonatalogy and the
survival of low birthweight infants: 65 per cent of babies
weighing less than 1000 g and 90 per cent of those weighing
between 1000 and 1500 g can be expected to survive.
Retinal vasogenesis commences from the optic disc at 16
weeks and is completed at only 36 weeks in the nasal retina and
only at term on the temporal side. Some 30-60 per cent of babies
born weighing less than 1500 g develop some ROP but sight-
threatening disease is confined to those infants with a gestational
age of less than 31 weeks and a birthweight of less than 1500 g.
It is generally accepted that ROP has multifactorial causes of
which prematurity and oxygen are the most important.
The disease process can be divided into a retinal and a
vitreoretinal phase and both of these phases can be divided into
either an active or a nonactive cicatricial phase. Acute ROP is
characterized by cessation of normal vasogenesis and the
formation of a demarcation line between the vascularized and
nonvascularized retina, soon to be followed by the development
of a poorly differentiated vasoproliferative lesion at the
demarcation line. Spontaneous regression of acute disease can
happen at any stage of development and the severity of
permanent cicatricial sequelae depends on the acute stage
reached before regression occurs. Only 1-2 per cent of cases run
the full course to total retinal detachment with spontaneous
regression in the remaining 98 per cent.
STAGING AND INTERNATIONAL CLASSIFICATION
The international classification is based on three factors: (1) the
degree of retinal vascular prematurity related to three retinal
zones, (2) the severity of disease expressed in increasing stages
from I to V and (3) the circumferential extent of disease
expressed in clock-hours. The zones are centred on the optic disc
with zone 1 circumscribed by an imaginary circle twice the optic
disc-fovea distance (a radius of 30°), zone 2 extending as a circle
demarcated by the nasal ora serrata/disc radius and temporally
by the equator and zone 3 represented by the remaining temporal
crescent outside zone 2. In Stages I- III the disease process is
confined to the retina. Further progression involves the vitreous.
Stages IVa (macula on) and IVb (macula off) represent the
cicatricial phase with localized traction retinal detachment. Stage
V represents end-stage disease with total retinal detachment.
The goal of screening is to identify and treat 'threshold' ROP.
This is defined as disease at stage III (ridge with extraretinal
fibrovascular proliferation) that involves zone 1 or 2 over five
contiguous or eight cumulative clock-hours or the presence of
THE RETINA: VASCULAR DISEASES I
'plus' disease in which the arterioles are tortuous and veins
engorged in the posterior pole. Argon laser photocoagulation
with the indirect ophthalmoscope of the peripheral nonperfused
retina should be undertaken in infants with 'threshold' disease as
these babies have a high risk of developing cicatricial retinal
detachment. Effective and economical screening can be achieved
by limiting screening to infants with a gestational age of 33 weeks
0 Zone 1 0 Zone 2 0 Zone 3
or less and weighing less than 1500 g. All such babies are
examined at 6-8 weeks after birth and again at a gestational age
of 36 weeks. Most cases of ROP develop between 32 and 44
weeks, and stage 3 occurs between 34 and 42 weeks; the more
posterior (zone 1 or 2) the involvement, the more rapid and
severe is the development. ROP that develops after 36 weeks is
unlikely to reach stage 3, as is ROP developing in zone 3.
Fig. 14.51 Diagram of ROP zones.
w hite line
nonvascularized retina
Fig. 14.52 In this baby with stage I ROP there is a thin white
demarcation line between vascularized and nonvascularized nasal
retina, signifying the onset of disease . This occurs at a gestational
age of approximately 32 weeks in the majority of cases.
By courtesy of Mr P Watts.
Fig. 14.53 In stage II the retinal lesion acquires volume and
projects out of the retinal plane.
By courtesy of Mr P U!Utts.
 RETINOPATHY OF PREMAtOkiTY

fibrovascular proliferation

demarcation line

Fig. 14.54 Stage III occurs at about 36 weeks of gestational age.

There is extraretinal fibrovascular proliferation from the posterior
edge of the ridge or posterior to it which projects into the vitreous,
which may be either segmental or continuous.
By courtesy of Mr P l¥Utts.

demarcation line

Fig. 14.55 'Plus' disease indicates activity. There is engorgement and increased tortuosity of the retinal vessels in the posterior pole, iris
vessel engorgement, pupil rigidity and vitreous haze . This stage is of great clinical importance as it precedes the onset of vitreoretinal
disease, which may be prevented by timely intervention. Severe ROP tends to progress rapidly and the window for therapeutic intervention
is short-about 2 weeks .
By courtesy of Mr P Watts.

laser burns

Fig. 14.56 Regression after laser photocoagulation is characterized by decreased congestion and tortuosity of the retinal vasculature;
formation of a brush border at the demarcation line; and a change in colour of the stage III retinal lesion from salmon pink to red as the
retinal lesion becomes more differentiated into a fibrovascular component and finally into white scar tissue.
By courtesy of Mr P l¥Utts.
56 THE RETINA: VASCULAR DISEASES I

,----=.-"""""""~-=--;----=~"""= vascu Ia rization of

peripheral retina

'open funnel' total

retinal detachment

Fig. 14.57 The onset ofvitreoretinal disease (stages IV and V) is signified by the sudden onset of a secondary vitreous haze in the
presence of stage III disease. With the onset of stage IVa (subtotal extrafoveal detachment) and IVb (with foveal detachment), retinal
ablation becomes ineffective and traction retinal detachment usually follows within 1 week. Progression to total retinal detachment (stage
V) usually occurs approximately at term, producing a vascularized white retrolental mass that must be differentiated from other causes of
leucocoria in an infant (e.g. retinoblastoma, congenital cataract, persistent hyperplastic primary vitreous, retinal colobomas or folds and
endophthalmitis).
By courtesy of Dr B Fantl.

Table 14.2 Sequelae of retinopathy of prematurity

Active retinopathy
Stage 1-111retinal phase
Inactive cicatrical phase Late complications
Tortuosity of vessels Nystagmus, microphthalmos
Dragging of disk and macula Glaucoma, corneal decompensation
Temporal retina l folds Retinal detachment
Myopia

Stage IV-V vitreoretinal phase Localized or total retinal detachment

Exudative retinal detachment
Vitreous haemorrhage

dragged macula

temporal retina

Fig. 14.58 Late cicatricial changes in eyes with vitreoretinopathy produce dragging of
the macula and temporal vessels towards the temporal periphery. Such eyes usually
have poor vision and nystagmus and may develop cataracts or retinal detachment from
peripheral lattice degeneration and hole formation in early adult life.
By courtesy of Mrs R Zakir.
 TRAUMATIC RETINOPATHY

TRAUMATIC RETINOPATHY

The retina can be damaged by excessive exposure to light, perforating injuries are discussed in Chapter 12 and drug toxicity
ionizing radiation or by contusion injury. Retinal tears and in Chapter 15.

Fig. 14.59 Solar burns are seen as minute central macular pits in the inner retina often just adjacent to the fovea in patients with a
history of sun-gazing, as in this LSD user. They probably result from uptake of blue light by the macular yellow xanthophil pigment. Visual
acuity is often quite good (from 20/30 to 20/40). Findings on fluorescein angiography are normal. Similar lesions are occasionally seen in
patients with no obvious history of solar exposure.

Fig. 14.60 Retinal oedema is a common finding following a

blunt injury to the eye (sometimes called commotio retinae,
Berlin's oedema). Any part of the fundus can be affected. The area
appears pale with a silvery sheen due to intraretinal oedema of the
outer retina. This usually resolves over a few days without sequelae,
although a careful examination of the retinal periphery for a
dialysis or break must be made (see Ch. 12). The possibility of
traumatic anterior chamber angle recession and future cataract
must not be overlooked.
THE RETINA: VASCULAR DISEASES I

choroida l rupture

subretinal haemorrhage

Fig. 14.61 More severe blunt trauma may produce a 'choroidal'

rupture affecting the choroid, Bruch's membrane and retinal pigment
epithelium but not the relatively elastic retina (these patients are
susceptible to later development of sub retinal neovascularization if the
injury affects the macular area; see Ch. 16) .

Fig. 14.62 Terson's syndrome. Preretinal haemorrhages from an acute rise in venous pressure can be seen as a result of subarachnoid
haemorrhage, strangling or a sudden Valsalva manoeuvre. Severe cases can produce intragel vitreous haemorrhage. This patient was a 37-
year-old woman who developed the retinopathy following a subarachnoid haemorrhage.

PURTSCHER'S RETINOPATHY

An acute retinopathy of peripapillary white intraretinal patches is
seen following severe crush injuries to the body; similar changes
are seen in patients with acute pancreatitis. Whether these
changes represent extensive microinfarcts, proteinaceous
exudation into the retina or a leucocytic retinal infiltration is
unknown and their aetiology is also controversial. Fat
embolization from bone marrow with extensive fractures has
been postulated but disseminated intravascular coagulation is
also present in these patients and is a possible cause. The
retinopathy can be asymmetrical and patients are often left with
patchy retinal dysfunction .
70 THE RETINA: VASCULAR DISEASES I

RADIATION RETINOPATHY

Radiation retinopathy usually presents 12-18 months after
inadvertent exposure of the retina to orbital or ocular
radiotherapy. The total dose of radiation received and the
amount of retina irradiated determines the extent of the damage
which is due to ischaemic vasculitis. The retinopathy is
characterized by signs of vascular occlusion that do not accord
with an anatomical vascular distribution; there is altered
permeability with cotton-wool spots, retinal haemorrhages and
oedema and later hard exudate. Fluorescein angiography shows
ischaemia with capillary closure and leakage in the affected area;
this may be confused with diabetic retinopathy. Extensive
retinopathy can progress to rubeosis. Photocoagulation may be
useful to prevent leakage from localized lesions, but no other
treatment has been shown to be effective. Radiation may also
cause an associated optic neuropathy.

Fig. 14.65 This patient received radiotherapy for an ethmoidal sinus tumour and presented 18 months later with an acuity of counting
fingers . Colour images show a localized area of ischaemia in the posterior pole that was inadvertently covered in the radiation field.
Fluorescein angiography demonstrates the area of ischaemia and leakage which does not correspond to an anatomical vascular distribution.
The eye eventually developed rubeotic glaucoma and became totally bind.
The Retina: Vascular
Diseases II
Jaheed Khan, Victor Chong, David Spalton

Diabetic Retinopathy
Sickle Cell Retinopathy
Systemic Lupus Erythematosus (SLE)
Retinal Vascular Anomalies
Retinoblastoma
472 THE RETINA: VASCULAR DISEASES II
DIABETIC RETINOPATHY
Diabetic retinopathy remains the commonest cause of blindness
in the working population and is the major cause of legal
blindness in this age group in the developed world despite the
present techniques of better medical control, ocular screening
and photocoagulation. Total blindness due to end-stage
proliferative diabetic retinopathy is now much less common but
unfortunately increasing numbers of diabetic patients become
visually impaired as a result of diabetic maculopathy. The natural
history of diabetic retinopathy is now well understood but the
sequence of the early biochemical and cellular events in the
retina is not.
Diabetes predominantly affects the microvascular circulation
of the retina and, apart from minimal venous dilatation in the
early stages, no changes are seen in the major retinal vessels.
Retinal blood flow is increased in the early stages of retinopathy
possibly as an autoregulatory response to tissue hypoxia. The
earliest structural changes are found in the retinal capillaries with
loss of mural pericytes, thickening of basement membrane, loss
of endothelial cells and capillary nonperfusion but the sequence
and interrelationship of these changes is uncertain. Capillary
basement membrane thickening is a common feature of diabetes
in many organs but the full range of microvascular changes is
unique to the retina and is not seen elsewhere in the body. The
retinal capillaries are supported by a plentiful population of
pericytes and a plausible hypothesis is that damage to these cells
plays a fundamental role in the genesis of retinopathy. Pericytes
support the capillary and also have an inhibitory influence on
capillary endothelial cell proliferation through cellular
transmitters. Capillary basement membrane thickening may
separate pericytes from endothelial cells. Capillary endothelium
is lost (some authorities believe this is the fundamental change)
and this is followed by non perfusion of the capillary and loss of
the retinal capillary bed. Microaneurysms are the hallmark of
diabetic retinopathy; although they are seen in a wide variety of
other retinopathies they never occur in the same profusion as in
VEGF
IGF-1 Abnormal
+-- Angiotensins Auto-regulation
L------.----~ FGF
Glycaemia Hypertension
diabetes. Potential causes for their appearance are mechanical
weakness of the capillary wall, capillary looping, proliferation of
endothelium, changes in haemodynamics or an abortive attempt
to perfuse adjacent retina. As the microvascular abnormalities
develop there is leakage of plasma, haemorrhage and vascular
shunting. Neovascularization seems to be controlled by a
complex interaction of many stimulatory and inhibitory factors
released from hypoxic retina, vascular endothelium, pericytes
and retinal pigment epithelium.
The underlying biochemical processes in diabetic retinopathy
are far from being understood. Chronic hyperglycaemia is
usually thought to be the underlying defect but the metabolic
abnormalities associated with diabetes are diverse. There appear
to be three major pathways of importance, these are the
glycosylation of proteins, the polyol pathway and the DAG- PKC
pathway. The nonenzymatic glycosylation of proteins by raised
levels of glucose appears to be of importance in the development
of capillary basement membrane thickening. The polyol pathway
in which aldose reductase converts intracellular glucose into
sorbitol through aldose reductase increases intracellular
osmolarity. Clinical studies have, however, cast doubt on the
importance of this pathway in human retinopathy. Diacylglycerol
(DAG) is produced during glycolysis; its concentration is
increased in diabetes and it is a potent activator of protein kinase
C (PKC), which regulates vascular permeability and plays a
significant role in the regulation of vascular endothelial growth
factor (VEGF), the best understood of the neovascular growth
factors. Other growth factors such as fibroblast growth factor,
pigment epithelium-derived factor and insulin growth factors,
also appear to be important in the neovascular response. PKC
inhibitors and VEGF modulators are currently under
investigation as potential treatments for diabetic retinopathy.
Clinical trials have shown that aspirin does not influence diabetic
retinopathy, suggesting that platelet aggregation is not an
important mechanism.
Fig. 15.1 Pathogenetic mechanisms in diabetic
retinopathy.
 DIABETIC RETINOPATHY 47

non perfusion
of ca pillaries

microaneurysm
ca pillary
loops

Fig. 15.2 (Top) These retinal trypsin digest preparations show early capillary damage and microaneurysms. (Top left) There are small
areas of capillary loss, many of the capillaries are acellular, and small microaneurysms can be seen along dilated and m ore hypercellular
capillaries. (Top right) More marked capillary dropout and well formed microaneurysms. (Bottom) An Indian ink injected preparation
showing capillary nonperfusion, capillary loops and microaneurysms.
Top figures reproduced with permission from The Retinal Circulation, edited by Wise, Dollery and Hawkin, Harper & Row, 1971 .
 DISEASES II

Fig. 15.3 An electron micrograph showing capillary basement Fig. 15.4 A trypsin digest preparation showing eosinophilic
membrane thickening and pseudopodia-like extensions into staining of degenerate capillary pericytes.
surrounding structures.

CLASSIFICATION OF DIABETIC RETINO PATHY

The initial clinical features of diabetic retinopathy are
microaneurysms, small retinal haemorrhages and small areas of
capillary closure (Table 15.1). Visual acuity is commonly normal
at this stage, although subclinical changes in colour vision and
contrast sensitivity might be found. This is followed by vascular
leakage, hard exudate and cotton-wool spots. Retinopathy may
progress to compromise vision in two ways: (1) maculopathy
develops with oedema, lipid exudation or ischaemia, or (2) a
proliferative retinopathy occurs, in which retinal hypoxia and
neovascularization predominate and reduce vision by vitreous
haemorrhage or traction retinal detachment. Not uncommonly,
both mechanisms coexist in the same patient. Diabetic
retinopathy is staged by its clinical features . Maculopathy is
classified by extent as focal or diffuse, and by mechanism as
exudative, ischaemic or mixed.

Table 15.1 Classification of diabetic retinopathy

Descriptive term
No diabetic retinopathy (DR)
Mild or moderate nonproliferative DR
Severe nonproliferative DR
Proliferative DR w ithout high-risk characteristics
Prol iferative DR with high-risk characteristics
Advanced proliferative DR
Features
Microaneurysms, retinal haemorrhages and exudate
Deep retinal haemorrhages in four quadrants, or venous beading or loops in two quadrants,
or t he presence of IRMAs
New vessels on the disc sma ller than one-third of a disc diameter without vitreous or
preretina l haemorrhages or new vessel elsewhere only
New vessels on the disc larger than one-th ird of a disc diameter or any new vessel with
vitreous or preretina l haemorrhages
Tractional retina l detachment, unresolved vitreous haemorrhage, rubeotic glaucoma
 DIABETIC RETINOPATHY

Diabetes

1
Pre proliferative retinopathy
(normal visual acuity)

r
Microaneurysms,

~
haemorrh ag es, hard exud ates

Proliferative retinopathy Maculopathy

Acuity lost from vitreo us Ac uity lost from macular

haemorrhage, t raction ret inal oed ema, ha rd exudate,
detachment, ca pillary clos ure ischaemia Fig. 15.5 A flow diagram illustrates the concept of progression
and neovasculari zatio n from initial nonproliferative or 'background' retinopathy to visual
loss from maculopathy or proliferative retinopathy.

NATURAL HISTORY

Visual loss is a late event in diabetic retinopathy. Retinopathy Careful monitoring of diabetic retinopathy when altering
normally develops many years after the onset of diabetes, glycaemic control is therefore critical. Pregnancy, renal disease
although in some adults it may be the first presenting sign of the and cataract surgery may worsen the retinopathy whereas high
disease. About 25 per cent of type I diabetics have some myopia, optic atrophy, glaucoma, central retinal artery occlusion
retinopathy after 10 years of disease, whereas type II diabetics and carotid artery stenosis appear to protect, possibly by
seem to develop retinopathy earlier with significant numbers reducing retinal metabolic demand (Table 15.2). Diabetic
being affected by 5 years after diagnosis and 50 per cent by 10 retinopathy is not seen before puberty.
years. Diabetics lose vision as a result of either maculopathy or
proliferative retinopathy. In general, type I diabetics are more
likely to have proliferative retinopathy whereas type II diabetics
are more likely to have maculopathy. More than 80 per cent of Table 15.2 Risk and protective factors for
visual loss in diabetics is due to maculopathy, due in part to the progression of retinopathy
10-fold greater number of type II patients. These patients lose Risk factors Protective factors
central vision but retain navigating sight. Proliferative Duration of diabetes High myopia
retinopathy is much more serious as about 70 per cent of these
eyes would be totally blind within 5 years from vitreous Poor long-term control Optic atrophy
haemorrhage and retinal traction detachment if left untreated. Tightening of poor control Glaucoma
Risk factors for the progression of retinopathy are the
duration of diabetes and the type (type I is worse than type II). Hypertension Carotid stenosis
Recent clinical trials have shown that meticulous long-term Pregnancy Retinal artery occlusion
glycaemic and blood pressure control retards the onset and
Renal failure
progression of diabetic retinopathy. Tightening poor glycaemic
control may, however, initially markedly worsen retinopathy and Hyperl ipidaem ia
cause neovascularization, possibly because initiating good
Puberty
control lowers retinal blood flow and exacerbates ischaemia.

MILD AND MODERATE NONPROLIFERATIVE DIABETIC RETINOPATHY (NPDR)

Previously termed 'background', this is the commonest form of
diabetic retinopathy. Microaneurysms, dot haemorrhages
(indistinguishable from microaneurysms without fluorescein
angiography) and small, deep, blotchy haemorrhages are seen in
the posterior pole and become more numerous as the retinopathy
progresses. Initially, NPDR tends to be most prominent in the
retina temporal to the macula, possibly because this is a
watershed area in the retinal circulation. Splinter haemorrhages
are a feature of combined hypertensive-diabetic retinopathy.
Small focal areas of closure in the capillary bed are common.
Hard exudates appear in relationship to focal vascular leakage,
and the occasional cotton-wool spot may be seen. Fluorescein
angiography shows more extensive changes than can be seen
ophthalmoscopically.
476 THE RETINA: VASCULAR DISEASES II

Fig. 15.6 This patient shows the

typical changes of early retinopathy
with scattered microaneurysms,
blot haemorrhages and hard
exudates and cotton-wool spots in
the posterior pole. The macula and
visual acuity are normal. The
retinopathy can fluctuate,
improving or deteriorating over a
period of time. Fluorescein
angiography demonstrates extensive
microvascular changes throughout
the posterior pole with scattered
microaneurysms and minimal
vascular leakage. Many more
micro aneurysms are visible that can
'dot and blot' haemorrhages be seen clinically. Although in some
areas capillary patterns around the
macula are irregular and show
minor areas of capillary closure,
they are, in the main, complete.

Fig. 15.7 With early retinopathy, the retina temporal to the macula is
often susceptible to earlier and more pronounced changes; elsewhere in
the posterior pole of this patient, retinopathy is comparatively sparse.

Fig. 15.8 These patients show a more marked nonproliferative retinopathy.

 DIABETIC RETINOPATHY

dilated ca pillaries

disappearance
of hard exudate vascular
disappearance remodelling
of some
microaneurysms
new microaneurysms

Fig. 15.9 Background retinopathy appearances can fluctuate and do not progress relentlessly. These photographs were taken 18 months
apart. The later photograph (top right) shows that the exudates temporal to the macula have been absorbed spontaneously and new
exudate has appeared inferior to the macula. Comparison of angiograms from the same patient shows there has been a considerable change
in the pattern of the microaneurysms. New microaneurysms have formed and others, on the temporal side of the macula in particular, have
disappeared over the same period of time .
178 THE RETINA: VASCULAR DISEASES II

SEVERE NONPROLIFERATIVE DIABETIC RETINOPATHY

Previously the stage between background and proliferative
retinopathy was called 'preproliferative diabetic retinopathy', but
is now termed severe or very severe nonproliferative diabetic
retinopathy. These patients have a substantial risk of progressing
to proliferative diabetic retinopathy (PDR). Severe or very severe
NPDR is characterized by signs of marked retinal hypoxia such
as cotton-wool spots, capillary nonperfusion, numerous
intraretinal haemorrhages, venous beading and loops, and
intraretinal microvascular abnormalities (IRMAs). Cotton-wool
spots have often been considered the hallmark of preproliferative
diabetic retinopathy, but the Early Treatment Diabetic
Retinopathy Study (ETDRS) found that IRMAs, venous
changes and many deep haemorrhages were more predictive of
imminent PDR. The retinopathy is defined as severe when one of
the following signs is present and as very severe when two ofthe
signs are present: (1) deep haemorrhages in four quadrants, (2)
venous abnormalities in two or more quadrants, and (3) IRMAs
in one or more quadrants.

Fig. 15.10 Numerous cotton-

wool spots, which persist for
longer in diabetes (up to 3
months) than with other causes
indicate marked retinal
ischaemia, as confirmed on
angiography.

Fig. 15.11 Areas of intraretinal

microvascular abnormalities (IRMAs)
with dilated tortuous veins along the
inferior temporal arcade are seen in
this patient. IRMAs represent
intraretinal neovascularization and are
found at the border of areas of
nonperfusion . They are entirely
intraretinal and do not leak
fluorescein . As they are associated
with nonperfusion it is not surprising
that they are associated with an
increased risk of PDR.
 non-perfusion (increased
size of foveal r--->r-____,.'-"-""i+---
fea t ureless retin a avascular zone)

Fig.15.12 Areas ofnonperfusion can often be recognized ophthalmoscopically by their flat featureless appearance and relative absence of
microvascular changes.

dark blotchy haemorrhage

.~---..,..__+__, diffuse cystic oedema

foveal avascular zone

Fig. 15.13 Blotchy, deep, retinal cluster haemorrhages are a feature of nonperfusion.
 ,------:::::=n='::;::--, r--="""'".....,._o--------, leakage from
major retinal
vessels
extensive
capillary closure
'normally'
'----=- -=-------' L_..:::::<====::::=-_ __j perfused retina
new vessels on disc
Fig. 15.15 This patient shows an extensive venous loop or 'omega anomaly'. There is
early neovascularization on the disc and deep cluster haemorrhages temporal to the macula.
PROLIFERATIVE DIABETIC RETINOPATHY {PDR)
This tends to occur in diabetics who have evidence of other
diabetic complications with renal, vascular and neurological
complications. The prognosis of these patients has improved
considerably in recent years with better medical management.
The stimulus for neovascularization, as in other neovascular
retinopathies, appears to be retinal hypoxia from extensive areas
of retinal capillary closure. This leads to a reduction of the
increased retinal blood flow which is a feature of nonproliferative
retinopathy. Neovascularization starts to appear from the
capillaries on the venous side of the circulation on either the
optic disc or retina, usually at the junction of normal and hypoxic
retina. At first the new vessels lie as vascular membranes flat on
the retinal surface, but induced changes in the vitreous gel cause
the gel to collapse and detach from the retina. New vessels that
have penetrated the internal limiting membrane are dragged
forwards on the posterior hyaloid face which acts as a scaffold for
Fig 15.14 Venous beading is seen where a vein
traverses an area of capillary nonperfusion.
veno us loo p
u v:=c-.,._~--.~ dark blotchy
haemorrhage
further proliferation. The neovascular tissue proliferates on the
posterior hyaloid face but does not penetrate the vitreous gel.
In common with neovascularization elsewhere in the eye these
vessels have fenestrated endothelial cell junctions and tend to
leak, while minor trauma and vitreous traction causes them to
tear and bleed to cloud the ocular media. Subsequent formation
of fibrous tissue produces traction bands between the retina and
posterior vitreous face; these eventually contract and detach the
retina (see Ch. 12) .
Clinically PDR is categorized by the location of
neovascularization, either on the optic disc (NVD) or elsewhere
(NVE), and by the presence of preretinal or vitreous
haemorrhage and fibrosis with retinal traction. Advanced
diabetic eye disease is characterized by vitreous haemorrhage and
tractional retinal detachment (see Ch. 12).
 DIABETIC

Fig. 15.16 This patient was a longstanding diabetic with renal

failure and poor vision (CF) in each eye. A composite mount of
the fluorescein angiogram of the right eye shows gross retinal
capillary closure and demonstrates how neovascularization tends to
arise on the retina at the border zone of the perfused and
ischaemic areas. This eye later developed rubeotic glaucoma.

i "'~-:>......,!-- f luorescein leakage

from neovascularization

Fig. 15.17 Retinal neovascularization begins as fine thready vessels that are difficult to see, usually adjacent to a vein. Angiography shows
them more clearly because of their leakage.
 A: VASCULAR DISEASES II

Fig. 15.18 More advanced changes are seen in these patients. Peripheral neovascular tissue is initially seen as a flat neovascular fan; in
more marked cases there is accompanying fibrous and retinal traction.

Fig. 15.19 Neovascularization on the optic disc carries a more serious visual prognosis than peripheral new vessel formation, and it is
therefore essential to detect this early. In common with all neovascular tissue, neovascularization leaks intensely on angiography; this sign
can, therefore, be very helpful in early diagnosis .
 DIABETIC RETINOPATHY

Fig. 15.20 Neovascularization starts as fine, flat, thready vessels on the disc that do not have a normal anatomical distribution. With time
it increases in extent and severity and with collapse of the vitreous gel is pulled forwards on the posterior hyaloid face.

New vessels pu lled forward

from optic disc

Fig. 15.21 This optic disc shows a prominent neovascular fan

which has been pulled forwards by the detached vitreous gel; the
vessels can be seen multiplying on the retrohyaloid face.
Movements of the gel with ocular movement will put traction on
these delicate vessels producing haemorrhage.
THE RETINA: VASCULAR DISEASES II

optic disc

Fig. 15.22 Histological examination shows vascularized fibroglial

tissue extending from the disc and adherent to the vitreous; note
that the neovascularization does not invade the gel.

Fig. 15.23 Preretinal and vitreous haemorrhages are a serious

complication of neovascularization both on the optic disc and in
the peripheral retina.

Fig. 15.24 This patient has marked neovascularization on the optic disc and
along the inferior temporal arcade. Vitreoretinal adhesions along the temporal
vascular arcades are very common in diabetes. Here localized fibrotic changes have
produced traction on the retina and distortion of the macula. If untreated the
natural history would be of further fibrotic tissue formation and traction,
progressing to localized or general traction detachment of the retina.
Fig. 15.25 In advanced cases vision is lost as a result of a combination of vitreous haemorrhage and traction detachment. In a few
patients, the retinopathy 'burns out' before this final stage and leaves inactive fibrotic tissue with varying distortion of the retinal
architecture. This patient, who never had photocoagulation, was left with visual acuities of hand movements and 20/60.

DIABETIC MACULOPATHY

Diabetic maculopathy is the leading cause of blindness in
diabetic patients, especially noninsulin-dependent (type II)
diabetics. It results from lipid exudation, oedema and ischaemia,
frequently in combination. The ETDRS used the term 'clinically
significant macular oedema' (CSMO) for the following signs:
retinal thickening (i.e. oedema) at or within 500 11m of the foveal
centre, hard exudates at or within 500 11m of the foveal centre if
associated with thickened adjacent retina or a zone of retinal
thickening covering at least one disc diameter (1500 !liD) within
one disc diameter of the foveal centre. Retinal thickening can be
satisfactorily assessed only by stereo-biomicroscopy; optical
coherence tomography (OCT) (see Chs 1 and 12) has an
increasing role in objectively assessing retinal thickness and the
response to treatment.

lipid and haemorrhage

seen more clearly on
red-free photograph

Fig. 15.26 Lipid exudation into the macula originates from a leaking vascular anomaly, usually a microaneurysm or area of capillary
closure, and spreads linearly in Henle's fibre layer. It is accompanied by oedema and thickening of the macula. Red-free photography shows
lipid and vessels more clearly and the angiogram shows that the leak originates from a microaneurysm surrounded by a small area of
capillary closure.
 ETINA: VASCULAR DISEASES II

circinate ring of
exudate involving
-h~---1 fovea (clinica lly
significant macular
oedema)
capillary dropout

Fig. 15.27 Circinate patterns of exudate form around leaking foci in more established cases. The angiogram shows the vascular
abnormalities in the centre of these lesions.

Fig. 15.28 Advanced exudative maculopathy results from prolonged and

untreated deposition of lipid within the macula. Circinate exudates coalesce to
produce massive plaques and although these will absorb if the sources of vascular
leakage are destroyed by photocoagulation neuronal destruction has occurred to
such an extent that vision rarely improves.
 DIABETIC RETINOPATHY

Fig. 15.29 Purely oedematous types of maculopathy are less common. Vascular changes produce macular oedema with relatively little
haemorrhage or exudation. These maculas have a thickened, rather amorphous, appearance and cystoid spaces are sometimes visible. These
changes are best appreciated by stereoscopic examination. Visual impairment is usually severe. Characteristically on angiography these
individuals show diffuse capillary dilatation over the whole posterior pole with relatively few focal changes. Later phases show massive
vascular leakage.

macular oedema

venous dilat ation

Fig. 15.30 Diabetic retinopathy can progress dramatically during pregnancy to maculopathy or proliferative disease. This patient had a
background retinopathy before her pregnancy but developed marked macular oedema so that acuity had fallen to 20/80 by 36 weeks when
labour was induced. At 3 weeks postdelivery (right) the oedema had resolved spontaneously and acuity improved to 20/30.
Fig. 15.31 With ischaemic maculopathy capillary closure produces deep intraretinal haemorrhage, oedema and ischaemia. Exudates are
comparatively sparse but may surround the central disturbance. The angiogram shows loss of the macular capillary circulation but the
patient still maintained an acuity of 20/80.

gross capil la ry closure

residual abnormal

Fig. 15.32 This series of angiograms shows three patients with increasing extensiveness of capillary closure and macular ischaemia. Visual
acuity is usually extremely poor and there is a high risk of progression to proliferative retinopathy.
 DIABETIC RETINOPATHY

DIABETIC PAPILLOPATHY

Fig. 15.33 This is an uncommon condition usually presenting with unilateral or bilateral optic disc swelling in a young adult diabetic. It
is often associated with signs of a mild optic neuropathy and only mild or moderate retinopathy. The aetiology is thought to be ischaemic
small vessel disease. The visual prognosis is generally good, with resolution without treatment.

MANAGEMENT OF DIABETIC RETINOPATHY

Many clinical studies have helped guide the management of
diabetic retinopathy. Rigorous control of systemic hypertension
has been shown to improve retinopathy and blood pressure
monitoring is essential for all diabetics. Mild or severe NPDR
without clinically significant macula oedema does not require
laser treatment. Exudative maculopathy with hard exudation
responds well to focal laser treatment of the leaking vessels.
Generalized macular oedema is more difficult to treat; grid
laser photocoagulation has been shown to be helpful. Ischaemic
maculopathy cannot be treated. The ETDRS did not find
aspirin (650 mg daily) to benefit or harm diabetic retinopathy
and thus aspirin can be safely used if needed for other
reasons. The study also found that hyperlipidaemia was
associated with a higher incidence of hard exudates indicating
that good serum lipid control is beneficial.
All eyes with neovascularization require panretinal
photocoagulation. This reduces the risk of severe visual loss by 50
per cent at 2 years and 70 per cent at 5 years. Some
ophthalmologists also treat all eyes with high-risk NPDR,
particularly if follow-up is difficult; others prefer to observe until
signs of neovascularization appear. The ETDRS showed that not
all eyes with PDR require urgent panretinal photocoagulation.
Eyes were shown to have 'high-risk characteristics' if they showed
signs of NVD larger than one-third of a disc area, NVD with
vitreous or preretinal haemorrhage, or NVE exceeding half a disc
diameter with vitreous or preretinal haemorrhage. Those eyes
with concomitant macular oedema or exudates should receive
additional focal laser therapy.
488 THE RETINA: VASCULAR DISEASES II

Fig. 15.31 With ischaemic maculopathy capillary closure produces deep intraretinal haemorrhage, oedema and ischaemia. Exudates are
comparatively sparse but may surround the central disturbance . The angiogram shows loss of the macular capillary circulation but the
patient still maintained an acuity of 20/80.

gross ca pillary closure

residual abnormal
_ ___,--t-,.-, capi llaries

Fig. 15.32 This series of angiograms shows three patients with increasing extensiveness of capillary closure and macular ischaemia. Visual
acuity is usually extremely poor and there is a high risk of progression to proliferative retinopathy.
 DIABETIC RETINOPATHY

DIABETIC PAPILLOPATHY

Fig. 15.33 This is an uncommon condition usually presenting with unilateral or bilateral optic disc swelling in a young adult diabetic. It
is often associated with signs of a mild optic neuropathy and only mild or moderate retinopathy. The aetiology is thought to be ischaemic
small vessel disease. The visual prognosis is generally good, with resolution without treatment.

MANAGEMENT OF DIABETIC RETINOPATHY

Many clinical studies have helped guide the management of
diabetic retinopathy. Rigorous control of systemic hypertension
has been shown to improve retinopathy and blood pressure
monitoring is essential for all diabetics. Mild or severe NPDR
without clinically significant macula oedema does not require
laser treatment. Exudative maculopathy with hard exudation
responds well to focal laser treatment of the leaking vessels.
Generalized macular oedema is more difficult to treat; grid
laser photocoagulation has been shown to be helpful. Ischaemic
maculopathy cannot be treated. The ETDRS did not find
aspirin (650 mg daily) to benefit or harm diabetic retinopathy
and thus aspirin can be safely used if needed for other
reasons. The study also found that hyperlipidaemia was
associated with a higher incidence of hard exudates indicating
that good serum lipid control is beneficial.
All eyes with neovascularization require panretinal
photocoagulation. This reduces the risk of severe visual loss by 50
per cent at 2 years and 70 per cent at 5 years. Some
ophthalmologists also treat all eyes with high-risk NPDR,
particularly if follow-up is difficult; others prefer to observe until
signs of neovascularization appear. The ETDRS showed that not
all eyes with PDR require urgent panretinal photocoagulation.
Eyes were shown to have 'high-risk characteristics' if they showed
signs of NVD larger than one-third of a disc area, NVD with
vitreous or preretinal haemorrhage, or NVE exceeding half a disc
diameter with vitreous or preretinal haemorrhage. Those eyes
with concomitant macular oedema or exudates should receive
additional focal laser therapy.
90 THE RETINA: VASCULAR DISEASES II

2000 equatoria l
laser burns
Fig. 15.34 Proliferative retinopathy requires treatment by
panretinal photocoagulation. By sparing the macular area
panretinal photocoagulation does not affect visual acuity. Some
2000 burns are usually given to the equatorial retina, normally in
one or two treatments, to produce regression of optic disc
Untreated neovascularization within a few weeks. A few patients require much
macular -+t-_.,,.r.-r.,;c,~>---~~. more treatment and all patients need to be followed up carefully
area with further treatment if neovascularization reappears. After
panretinal photocoagulation visual disability is surprisingly slight.
Preservation of the inner nerve fibre layer avoids the production of
arcuate field loss and patients normally notice only marginal
constriction of their visual field and sometimes a reduction in their
visual performance in the dark. It is essential that patients are
counselled about the effect of panretinal photocoagulation on their
ability to drive especially on the right.

loss of
photoreceptors

RPE damage

Fig. 15.35 The histology of a laser burn shows that there is atrophy of the retinal pigment epithelium (RPE) and photoreceptors in the
area of the burn. The energy is taken up in the RPE and, provided the amount of energy is restricted, the thermal injury is localized and
the inner nerve fibre layer spared. Damage to this layer would result in nerve fibre damage and visual field defects.
By courtesy of Professor J Marshall.
 DIABETIC RETINOPATHY

chorioretinal atrophy
from excessive treatment

Fig. 15.36 In practice, the burns must be of sufficient intensity to produce a soft white reaction in the retinal pigment epithelium; a
dense white reaction indicates damage to the inner retina. Within a few days the burns become pigmented atrophic scars (middle).
Photocoagulation that is excessive leads to damage of the RPE and subsequent atrophy (right), causing peripheral field constriction and
night blindness.

chorioretinal .------co~--,.-=-----,
atrophy from retrohyaloid
xenon arc photo- , haemorrhage
coagulation
gross forward
~~--"'-'---1 neovascular-
ization from
optic disc

Fig. 15.37 The efficiency of panretinal photocoagulation is demonstrated by this patient who participated with informed consent in a
controlled trial of panretinal photocoagulation in the early 1970s. (Left pair) Early neovascularization is seen on each optic disc, confirmed
by the presence of leakage on the fluorescein angiogram. The right eye was treated with xenon arc photocoagulation and the left rem ained
untreated as a control eye . (Right pair) Fifteen months after panretinal photocoagulation to the right eye, the new vessels on the optic disc
have regressed and marked chorioretinal scars can be seen from the photocoagulation (excessive treatment by present standards). Visual
acuity remained normal in this eye, with loss of peripheral visual field and night blindness. In contrast the left deteriorated to perception of
light with a marked neovascular membrane arising from the optic disc with total traction retinal detachment. This eye now has a substantial
risk of developing rubeotic glaucoma.
 RETINA: VASCULAR DISEASES II

Focal
photocoagu lation
to leaking vesse ls i n-+-----...--------=-~
centres of ci rci nate
exud ates

Fig. 15.38 Exudative maculopathy is treated by obliterating

the leaking microvascular abnormalities that produce the hard
exudate . These can often be identified clinically without the
need for routine fluorescein angiography. Absorption of hard
exudates takes several weeks, depending on their extent.

absorbing
hard exudate

Fig. 15.39 Fundus appearance (left) before and (middle) after laser photocoagulation. Before treatment, early deposition of hard exudate
can be seen in the macular area. Eight weeks after treatment the exudate is in the process of being absorbed; 1 month later it has
disappeared and the scars in the retinal pigment epithelium from the photocoagulation can be seen. Such treatment does not produce any
visual impairment as long as the burns are outside the foveal avascular zone and of sufficiently low intensity to protect the overlying retinal
nerve fibres .
 SICKLE CELL RETINOPATHY

thickened macula

Fig. 15.40 Macular oedema is treated by putting a grid of gentle photocoagulation over the macular area, taking care to avoid the fovea.
Some 12 weeks after treatment the oedema has considerably resolved.

SICKLE CELL RETINOPATHY

A neovascular retinopathy that predominantly affects the
peripheral retina is a feature of the sickle cell diseases (HbSS,
HbSC, sickle thalassaemia). Retinal changes are most commonly
seen with HbSC or S Thai disease, probably because these
patients are less anaemic and consequently have a higher blood
viscosity than those with the other sickle diseases. Patients with
the sickle cell trait (heterozygotes) do not develop retinopathy.
Thrombotic arteriolar occlusions appear to be the basic
pathological lesion. These occur in the equatorial retina,
probably as a result of the combination of decreasing Po 2 , which
induces sickling, and decreasing blood vessel diameter. Retinal
haemorrhages and capillary closure follow the occlusions,
sometimes with subsequent peripheral neovascularization.
Occasionally patients are seen with visual loss from occlusion of
a macular arteriole. The neovascular fronds tend to autoinfarct.
Vitreous haemorrhage and traction retinal detachment are
comparatively uncommon, especially when considered as a
proportion of the total number of affected patients.
Photocoagulation is controversial; it can reduce the frequency of
vitreous haemorrhage but does not affect the final visual
outcome. In general, laser therapy is not required for most
patients, although it might be justified for those with frequent
vitreous haemorrhages
 arteriole
occlusions

arteriol e
occlusions

Fig. 15.41 Fresh peripheral arteriolar occlusions can be seen in this eye.

Fig. 15.42 Acute arteriolar vascular occlusions can produce intraretinal or subretinal haemorrhage (salmon patches), which are red or
yellowish and about one disc in diameter. They are seen in the equatorial retina adjacent to the occluded arteriole and are a sign of recent
infarction causing necrosis of the vascular wall and haemorrhage. If the RPE is damaged they resolve to leave a pigmented scar (black
sunburst).
 SICKLE CELL RETINOPATHY

Fig. 15.43 Neovascularization

occurs in the peripheral retina along
the demarcation between perfused
and nonperfused retina. Early changes
are seen in this patient. Abnormal
peripheral closure vascular shunts in the peripheral
retina are common. Sickle cell
retinopathy is common in the West
Indies; these neovascular fans are
known as 'sea-fans', reminiscent of
the local coral formations.

peripheral
closure

Fig. 15.44 This patient shows inactive fibrotic changes in the

peripheral retina. Vitreous haemorrhage and retinal detachment are
uncommon in sickle cell retinopathy probably because the lesions
tend to infarct spontaneously. Most patients can be watched
without treatment. Photocoagulation of fronds does not appear to
improve the natural history of the disease and may make the
disease move more centrally.
 t racti ona l retina l
YJ \,\,~=1
detach ment

Fig. 15.45 Occasionally some patients lose vision as a result of vitreous

haemorrhage and retinal traction.

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Retinopathy from SLE occurs as a combination of microvascular
ischaemia from vasculitis and changes from secondary systemic
hypertension, anaemia and thrombocytopenia. Choroidal
infarcts can be seen and occasionally acutely ill patients present
with bullous subretinal fluid from choroidal involvement due to
acute systemic hypertension or vasculitis. Scleritis is common
(see Ch. 5) but uveitis does not occur. The predominant features
of SLE retinopathy are cotton-wool spots in the absence of
hypertension and retinal haemorrhages and Roth's spots,
especially in patients with haematological changes.
Antiphospholipid antibodies are found in many patients with
SLE; these are associated with systemic venous thrombotic
episodes and may also contribute to the retinopathy in some
patients.
 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Fig. 15.46 Skin lesions are common with SLE. A vasculitic facial rash in a
'butterfly' distribution is the most common manifestation.
By courtesy of Dr G R V Hughes.

f resh cotton-
wool spots

Fig. 15.47 This 14-year-old boy presented with acute lupus,

renal failure and dementia from cerebral involvement and died
from renal failure. Both fundi show numerous cotton-wool spots.

dilation and
leaka ge f rom
\'::::~~~t----" vei n in area of
occluded artery non-perf usion

Fig. 15.48 This patient with severe SLE shows the more unusual
sign of arteriolar occlusion.
 retinal artery
occluded by RPE
amorphous
eosinoph ilic
material sclerosed
choroidal artery

photoreceptor
nuclei

Fig. 15.49 Histological examination from a patient with similar

retinal signs to those seen in Fig. 15.45 shows an occluded retinal
arteriole, with no evidence of vasculitis, and sclerosed choroidal
vessels as a consequence of systemic hypertension. In the choroid
there is a marked lymphocytic infiltrate.

patches of
r~i'=~:.__!:~-::z~m pa lish deep
r fl uffy RPE
swellings

Fig. 15.50 This severely ill patient with an acute exacerbation of

SLE presented with blurred vision. Fundus examination shows
subretinal fluid and RPE changes from choroidal vasculitis.
 RETINAL VASCULAR ANOMALIES 49

RETINAL VASCULAR ANOMALIES

RACEMOSE MALFORMATIONS

These are thought to be developmental rather than genetic in syndrome affects the choroidal vessels rather than the retinal
ongm. Rarely, retinal arteriovenous malformations or circulation (see Ch. 9). Visual loss from vascular leakage,
anastomoses can be associated with intracranial vascular accumulation of hard exudates or haemorrhage is rare .
abnormalities (Wyburn-Mason syndrome) . Sturge- Weber

Fig. 15.51 Arterial loops can be seen projecting forwards from

the disc. They occasionally undergo torsion, causing retinal
infarction.

Fig. 15.52 Small localized vascular abnormalities may be discovered as an incidental finding on
routine examination. This patient has a small arteriovenous malformation adjacent to the optic
disc.

arterioveno us
~~04'----.W malformation
overlyin g macula

Fig. 15.53 Larger arteriovenous malformations have a dramatic

fundal appearance. They are normally totally static, but visual
acuity will be affected if the macula is involved, as in this patient.
 : VASCULAR DISEASES II

CAVERNOUS HAEMANGIOMA

>J
late phase
angiogram showing
residual dye in the ~'-----""""'""'*'¥~
saccular aneurysms

Fig. 15.54 Cavernous haemangioma of the retina is a rare benign lesion. It consists of isolated clusters of dilated blood vessels within a
fibrous matrix. The lesions do not progress or generally cause symptoms and are not associated with any systemic vascular disease. Well
documented cases have been shown to remain unchanged over many years. The fluorescein angiogram shows that the dilatations fill with
dye in the late venous phase, often with a fluid level from the stagnant circulation (fluorescein on top of the stagnant red blood cells), but
with no vascular leakage.

VON HIPPEL-LINDAU DISEASE

This is a dominantly inherited disease with variable penetrance.
Characteristic retinal haemangioblastomas are associated with
similar lesions in the cerebellum, renal carcinoma and
phaeochromocytomas, as well as renal and pancreatic cysts.
Patients require lifelong screening with magnetic resonance
imaging (MRI) to detect intracranial lesions, and renal
ultrasonography to detect renal carcinoma and biochemistry for
phaeochromocytomas. Genetic counselling of affected families is
important. The gene has been identified and characterized as a
tumour suppressor gene on the short arm of chromosome 3.
Retinal haemangioblastomas are the commonest
manifestation of the syndrome; they can occur at any age but
most present around 20- 30 years of age. They are frequently
bilateral and may be multiple in the same eye. About 70 per
cent of patients who carry the gene will have developed them by
the age of 60 years. Retinal haemangioblastomas have a
progressive course of enlargement and leakage or rupture to
produce lipid exudation or vitreous haemorrhage with
significant ocular morbidity. In view of the complications these
lesions should be treated with photocoagulation or cryotherapy,
and the patient must be observed constantly as, with time, new
lesions may develop. Photodynamic therapy has a potential
therapeutic role.

ang ioma

Fig. 15.55 Early tumours are seen in the peripheral retina as red
or yellowish bulbous vascular lesions with enlarged feeder vessels.
Fluorescein angiography can be very helpful in detecting early
lesions which are easily obliterated by photocoagulation.

massive feeder vessels
Fig. 15.56 These tumours can reach dramatic proportions.
Fluorescein angiography demonstrates the feeder vessels and the
large leaking tumour. A shallow retinal serous detachment may
occur around large tumours.
COATS' DISEASE, LEBER'S MILIARY ANEURYSMS AND PARAFOVEAL TELANGIECTASIA
Many retinal specialists consider Coats' disease, Leber's miliary
aneurysms and parafoveal telangiectasia to be variations of the
same disease spectrum but affecting different age groups. The
aetiology is unknown, but, in some patients at least the pathology
appears to be related to somatic expression of the dominant
X-linked gene for Norrie's disease.
Coats' disease usually presents in boys aged 8-10 years as a
uniocular disease in which saccular aneurysmal malformations
produce massive subretinal exudation and visual loss. In
childhood, Coats' disease must be distinguished from
retinoblastoma or toxocariasis.
RETINAL VASCULAR ANOMALIES
retina elevated
over haemangioblastoma
Fig. 15.57 This patient has a haemangioblastoma within the
optic disc.
By courtesy of Dr A webster
Similar vascular lesions are described as Leber's miliary
aneurysms when they present in young adults, usually with less
telangiectasia, retinal exudation and destruction.
Parafoveal telangiectasis usually presents as macular oedema
or exudates in middle age associated with aneurysmal and coarse
ectatic dilated parafoveal capillaries. Telangiectasia may be
present in the peripheral fundus. Patients with macular oedema
and exudates sometimes benefit from laser treatment although
spontaneous resolution may also occur.
 502 THE RETINA: VASCULAR DISEASES II
==I

tel angiectatic vessels

o-1-'--'e,!,.i.d...,i.,H coarse dilated capi llaries

"'"'c !.---"""'
,o,.!l.,;;;~~rl telang iectatic vessels

~---/-'-------1 vascular closure

Fig. 15.58 This boy has massive subretinal exudates associated with a localized area of vascular malformation, which leaks in the later
phase of the angiogram.
 RETINAL VASCULAR ANOMALIES

Fig. 15.59 Massive subretinallipid exudate and serous retinal

detachment in a young boy with Coats' disease can simulate a
retinoblastoma. Apart from the difference in age of presentation,
the differential diagnosis is aided by demonstrating the vascular
anomalies and the yellowish-green lipid exudate, in contrast to the
white or pink fleshy appearance of retinoblastoma.

Fig. 15.60 Lipid-containing exudate fills the subretinal space and

the retina is totally detached. Histological examination shows
telangiectatic vessels in the retina and proteinaceous and lipid-
containing exudate in the retina and subretinal space.

Fig. 15.61 Peripheral

miliary aneurysms in
another patient.
Fluorescein angiography
demonstrates the saccular
vascular dilatation
accompanied by
coarseness and closure of
the capillary bed. Massive
leakage of dye occurs in
the late phases, although
some degree of capillary
closure occurs retinal
neovascularization is not
seen.
Fig. 15.62 Parafoveal telangiectasia presents with distortion, macular oedema and serous retinal detachment in this middle-aged man,
who presented with visual blurring in the right eye. Fluorescein angiography in the early phases demonstrates dilated telangiectatic
capillaries adjacent to the macula; these leak slowly as the angiogram progresses. Such patients require a careful examination of the
peripheral retina for occult vascular abnormalities. Patients can be helped by photocoagulation to the abnormal vascular tissue.

RETINOBLASTOMA

Retinoblastoma is the third commonest ocular malignancy after
choroidal malignant melanoma and metastases and although rare
it is one of the most common malignancies of childhood
(together with leukaemia and neuroblastoma). About 1 per cent
of childhood deaths from cancer are due to retinoblastoma. The
genetics of retinoblastoma are complex and historically
interesting, as the concept of a tumour suppressor gene was first
proposed and later proved in seeking to explain hereditary
retinoblastoma. The disease is inherited as an autosomal
dominant condition in about half of patients but occurs
sporadically in the other half, usually as a solitary tumour in one
eye. Inherited cases tend to be younger and to be bilateral with
more than one tumour in the eye. The incidence of
retinoblastoma is about 1 in 20 000 live births. Retinoblastoma
can present at birth but the mean age of presentation is 8 months
for those with genetically inherited disease and 25 months for
sporadic cases; 90 per cent of cases have presented by 3 years of
age and the tumour is extremely rare after the age of 7 years. A
high incidence of second primary tumours such as osteogenic
sarcoma is seen in survivors. Patients present with a normal-sized
eye for their age with leucocoria, squint or visual loss, and less
commonly with hypopyon, hyphema, uveitis, buphthalmos or
metastases. The tumour may undergo spontaneous regression;
these lesions are sometimes considered to be benign tumours
and have been called 'retinomas'.
Genetic counselling is mandatory and requires a thorough
examination of both parents and all siblings (Table 15 .3) . The
variable penetrance of dominantly inherited disease means that
without genetic analysis, a definite answer cannot be given as to
whether an isolated unilateral case is sporadic or familial. The
parents can be given the statistical risk of further siblings being
affected, an affected child transmitting the gene to the next
generation, or the chances of an unaffected sibling being an
asymptomatic carrier.
 Table 15.3 Genetic counselling in retinoblastoma
Risk(%)
Type of case Bilateral familial Unilateral familial Bilateral sporadic Unilateral sporadic
Further siblings having affected eyes 40 40 5.7 0.6
Unaffected siblings being carriers 10 10 very low very low
Unaffected carriers' children being affected 7 7 very low very low

Affected patients'children being affected 40 40 40 8

Gametes Body Eye

2nd ocular
All cells envi ro nm enta l 'hit'
Genetic mutation or
parental transmission of
abno rmal chromosome 13
carry gene
y
~ l .\2V
(13'\ Multiple RB

L--------- -+• Genetic transmission

2 environmenta l 'hits' on a single reti na l cel l

Normal chromosome 13
Nmm'Gp-ic_c_e-lls_l:.......:l::....__.... ® Solitary RB

• No genetic transm ission

Fig. 15.63 Retinoblastoma is linked to deletion of a tumour suppressor gene known as RBI on the long arm of chromosome 13. Only
one normal copy of the gene is required to suppress retinoblastoma. In familial cases, one allele of the tumour suppressor gene is already
inactivated in the germline so that all cells in the body are affected but the other copy remains active to continue production of tumour
suppressor protein (heterozygote). Loss of the second allele, however, abolishes this production and leads to unregulated growth; this is
considered the second hit ofthe 'two-hit hypothesis' . Thus, paradoxically, although retinoblastoma is dominantly inherited, the way in
which a cell develops malignancy is 'recessive' as both copies of the gene need to be inactivated. Sporadic cases of retinoblastoma develop
when both alleles are inactivated, either by new genetic (i.e. not inherited in the germline but inheritable to new generations) or somatic
(nonheritable) mutation. About 30 per cent of all sporadic disease is thought to be due to new genetic mutations. Environmental factors
such as viral infections are believed to be responsible for somatic mutations.

Fig. 15.64 Bilateralleucocoria is seen in a 1-year-old child with

gross bilateral ocular involvement. A convergent squint is present.
Other common causes of leu co coria in childhood are retinopathy
of prematurity (see Ch. 14), persistent hyperplastic primary
vitreous (see Ch. 8), toxocariasis (see Ch. 10), coloboma (see Ch.
17) and Coats' disease (see Fig. 15.56).

Fig. 15.65 In common with any other bilaterally blinding

diseases of childhood, affected children poke and rub their eyes,
probably to obtain some visual sensation by the production of
phosphenes from manual stimulation.
 11 IL ilL 1 ihA. VAJCOLAR DISEASES II

Fig. 15.66 This child has a buphthalmic left eye with a white pupil.
By courtesy of Mr J Hungerford.

Fig. 15.67 Following chemotherapy and laser thermotherapy this tumour has become flatter, whiter and more circumscribed indicating
regression of the tumour.
By courtesy of Mr J Hungerford.
 RETINOBLASTOMA

Fig. 15.68 This child has massive subretinal tumour. Growth into the gel is known as an endophytic tumour whereas subretinal spread
is known as an exophytic tumour. Most tumours show both components. Rarely, tumours may spread diffusely in the retina. Calcification is
common, occurring in areas of necrosis within the tumour and this is a helpful diagnostic sign which can be recognized
ophthalmoscopically as chalky white areas and confirmed by ultrasonography or CT scanning. Following chemotherapy this tumour has
become white, calcific and well circumscribed indicating a good response to the treatment
By courtesy of M r J Hungeiford.

Fig 15.69 This child shows vitreous seeding following a relapse

after chemotherapy
By courtesy of Mr J Hungeiford.

PATHOLOGY

Retinoblastomas are derived from totipotent germinal
retinoblasts or possible photoreceptor progenitor cells. They
show varying degrees of differentiation ranging from anaplasia to
the formation of rosette- and fleurette-shaped structures which
represent an attempt at differentiation into photoreceptors.
Necrosis and calcification are common findings. Extraocular
extension occurs mainly by infiltration of the optic nerve spread
into the brain but there may also be infiltration of the orbit.
Blood-borne metastases may develop in the lungs and in bone.
Patients are best managed by those with special experience of
retinoblastomas. Small intraocular tumours can by treated
conservatively by localized photocoagulation, cryotherapy or
radiotherapy to preserve vision but large tumours or those with
suspected optic nerve involvement necessitate enucleation. It is
essential at enucleation to remove as much optic nerve as
possible and to examine transverse sections of the nerve to
ensure that the residual nerve is free from tumour. Patients in
whom retinoblastoma has spread outside the eye have a very poor
prognosis.
 exophytic growth
(into the subreti nal endophytic growth
space) (into vitreous)

Fig. 15.70 Section of an enucleated eye showing both endophytic and exophytic
growth of tumour.

tumour
infil lrat ion

Fig. 15.71 Optic nerve invasion by retinoblastoma: longitudinal section (left) and
transverse section (right) .
tumour
infiltration
 RETINOBLASTOMA

Fig. 15.72 Many retinoblastomas are undifferentiated but some show differentiation as a primitive attempt to form photoreceptor cells.
This is exemplified by Flexner-Wintersteiner rosettes (left) and fleurettes (right).
Retinal Degenerations
Jaheed !<.han, Victor Chong

Retinal Dystrophies
Michel Michaelides, Anthony Moore

Age-related Macular Degeneration

Treatment of Age-related Choroidal Neovascularization
Idiopathic Polypoidal Chorioretinopathy {IPCV)
Central Serous Retinopathy
Inherited Retinal Dystrophies
Inherited Central Receptor (Macular) Dystrophies
Inherited Retinal Dystrophies with Generalized Retinal Involvement
Progressive Retinal Dystrophies
Inherited Chorioretinal Dystrophies
Neurodegenerative Disorders
Drugs Causing Retinal Toxicity
12 RETINAL DEGENERATIONS AND DYSTROPHIES
Normal vision depends on the proper functioning of the macula
which, when disturbed by disease, affects central vision and often
causes th~ patient to present for the first time. Central distortion
of vision (metamorphopsia) or minification of the image are
pathognomonic for macular disease. Other symptoms apart from
loss of acuity include photophobia, glare and dazzle (which can
be severe), poor colour perception, night-blindness and a central
or paracentral scotoma. Macular disease in infants frequently
presents as congenital nystagmus.
Classifying macular disease by the anatomical layer that is
primarily affected- choriocapillaris, Bruch's membrane, retinal
pigment epithelium (RPE), photoreceptors or neuroretina- is a
commonly used and helpful way to conceptualize and diagnose
retinal problems. Stereoscopic examination of the fundus with an
indirect biomicroscopy lens through a dilated pupil is essential to
assess the location of a lesion within the retina and its
relationship to the superficial retinal vessels. However, although
examination can infer the initial site of the lesion in many retinal
diseases the primary defect cannot be precisely localized to a
single cell layer as defects in one retinal layer produce changes in
adjacent structures. For example, retinitis pigmentosa is
associated with photoreceptor degeneration and also RPE and
choriocapillaris atrophy with later neuroretinal degeneration and
vascular attenuation. Our understanding of the pathogenesis of
various retinal diseases has improved in recent years with
advances in molecular genetics and cell biology and some
diseases that were thought to affect, for example, primarily the
photoreceptors have now been shown to have their defect in the
RPE . Fundus photography, fundus fluorescein angiography
(FFA), indocyanine green (ICG) angiography, optical coherence
tomography (OCT) and autofluorescence (AF) imaging are
valuable investigations for diagnosis and documentation. Many
AGE-RELATED MACULAR DEGENERATION
This is the commonest cause of legal blindness in the developed
world. It predominantly affects the elderly Caucasian population
and is much less common in other races. The hallmarks of age-
related macular degeneration are drusen, RPE atrophy and
choroidal neovascularization.
Major studies have devised various systems for describing the
fundus changes. Age-related maculopathy (ARM) and age-
related macular degeneration (AMD) distinguish early disease
from end-stage disease. ARM describes drusen and/or RPE
abnormalities. AMD is subdivided into dry (geographical RPE
atrophy without neovascularization) or neovascular (RPE
detachment, haemorrhages and/or scarring due to choroidal
neovascularization (CNV) forms. The Age Related Eye Disease
Study (AREDS) subdivides ARM into four categories and allows
rapid classification. Drusen type is divided into small ( <63 mm),
intermediate (63 to 124 mm) and large (greater than 124 mm).
Atrophy of the RPE is either centred or noncentered (not
involving the fovea) .
CNV occurs as 'classical' or 'occult' forms. In classical CNV,
fluorescein angiography shows a well demarcated neovascular
membrane with hyperfluorescence that progressively leaks dye
from early on to obscure the lesion's boundaries over time.
Occult CNV is associated with late leakage from an
macular lesions are small and produce scotomas that are difficult
to demonstrate; an Amsler grid can help in these cases.
Electrodiagnostic tests and psychophysical testing are time
consuming but very useful for diagnosing, documenting and
assessing the prognosis of inherited retinal disease (see Ch. 1).
Occasionally deciding whether visual loss is caused by
macular or optic nerve disease can be difficult as both reduce
acuity and colour vision and can cause central scotomas. Retinal
lesions tend to produce a 'positive' scotoma in which patients are
aware of dark obscuration or something in front of their vision in
contrast to the 'negative' scotoma of neurological disease (for
example, patients do not notice a hemianopic field defect as
'dark') . An afferent pupillary defect indicates optic nerve disease
unless the macular lesion is extensive. Another useful and easily
performed test is the photostress test in which recovery of visual
acuity following dazzle with a bright light is delayed with macular
lesions whereas vision recovers normally with optic nerve
disease. Retinal lesions produce a blue-yellow pattern of colour
deficit in contrast to the red-green pattern of optic nerve disease
(see Ch. 19). These clinical tests are subjective, however, and less
reliable than pattern electroretinography (PERG) which in most
cases can distinguish macular from optic nerve disease (see
Ch.1).
Most retinal dystrophies and degenerations are untreatable
and any treatment measures are largely supportive in the form of
low visual aids. Perhaps the most important aspect of
management is to establish a correct diagnosis as this aids
prognosis; genetic and occupational counselling are very
important. It is unusual for macular diseases to progress to total
blindness and patients are often reassured to know this; most will
have a central scotoma with good peripheral vision and are able
to lead independent lives.
undetermined source at the level of the RPE. It can also appear
as a fibrovascular pigment epithelial detachment which is seen on
fluorescein angiography as early (less than 2 minutes) stippled
hyperfluorescence representing irregular RPE elevation. The
Treatment of Age Related Macular Degeneration with
Photodynamic Laser Study (TAP) subdivided CNV into
predominantly classical (more than 50 per cent of CNV lesions
with a classical component), minimally classical (less than 50 per
cent classical) and purely occult (no classical CNV).
PATHOGENESIS OF AMD
AMD appears to result from defects in the RPE cell- Bruch's
membrane-choriocapillaris complex and is thought to be a
collection of heterogeneous disorders associated with multiple
genetic and environmental factors . Much current research
centres on defects in the RPE cell and Bruch's membrane (see
Ch. 13). In normal ageing progressive thickening of Bruch's
membrane occurs with accumulation of lipids, noncollagenous
proteins and other extracellular material such as advanced
glycation endproducts, collagen and elastin changes and
increased calcification. By the fourth decade all eyes show

accumulation of membranous debris within both collagenous
layers. With time, a second series of changes is seen with
deposition of diffuse material both between the RPE and its
basement membrane (basal linear deposit) and between the
basement membrane and the inner collagenous layer (basal
laminar deposit). The latter can become extensive with a complex
morphology and may be confused with diffuse or soft drusen,
drusen being focal accumulations between the RPE basement
membrane and the inner collagenous layer of Bruch's
membrane. Lipofuscin accumulates with age in the RPE cell
from metabolism of photoreceptor outer segments from
oxidative damage or RPE overloading by failed photoreceptors.
The specific mechanisms underlying these changes are not fully
understood, but it is thought that the resultant increase in
thickness and reduction in molecular transport through Bruch's
membrane and the RPE cell may contribute to photoreceptor
cell death and AMD. In addition, anatomical changes and
delayed filling on fluorescein angiography are seen in the
choroidal circulation.
Fig. 16.1 Histological examination shows the pathological appearances of hard (top) and soft (middle) drusen. Preparations stained to
demonstrate TIMP3. The red stain demonstrates its presence in the drusen and along Bruch's membrane (bottom). Note the patchy loss of
the RPE over the drusen .
AGE-RELATED MACULAR DEGENERATION
AMD can be dominantly inherited and many classical
features of AMD (drusen, pigment epithelial detachment (PED),
CNV, atrophy) are also seen in inherited disorders such as
Sorsby's fundus dystrophy, North Carolina macular dystrophy,
and Doyne's dominant drusen, suggesting common underlying
cellular mechanisms between these dystrophies and AMD.
These are important for the potential clue that they give to
the underlying cellular process involved. In Stargardt's macular
dystrophy, mutation of the ABCA4 gene causes lipofuscin to
accumulate in RPE; a similar process might occur in AMD
leading 'to RPE dysfunction and eventual death. In Sorsby's
fundus dystrophy, mutation of the TIMP3 gene (tissue inhibitor
of metalloproteinase 3 inhibits matrix degradation) is associated
with thickening of Bruch's membrane. In AMD, TIMP3
concentration is also increased and associated with thickening of
Bruch's membrane. Increased lipid deposition is also found in
Bruch's membrane and epidemiological risk factors for cardiac
disease (although not serum cholesterol) are also associated with
A MD.
irregularity and
hyperplasia of RPE
Bruch's membrane
irregularity of RPE
--~----- ___ __...-------- ....____ _
...____ ....... __ .. ....... _______ .....---·------···-................_
~
RETINAL DEGENERATIONS AND DYSTROPHIES

normal RPE cell

atrophic RPE cells

..ti»-.=1!>""<., elevated over drusen

photoreceptor
Bruch's membrane outer segments

thickened Bruch's ~=<=======v=:::'::::===1

membrane
0

Fig. 16.2 Scanning electron micrograph of a 45-year-old eye shows RPE cells distended with lipofuscin granules (middle). The RPE is
stretched over a large drusen (top), which can be seen to contain lipofuscin granules (bottom).

DRUSEN AND ATRUPHIC MACULAR CHANGES
Drusen lie in Bruch's membrane and stain progressively during
fluorescein angiography. They are assessed more easily by
fluorescein angiography than by fundoscopy as angiography
shows RPE atrophy more clearly. Different drusen staining
patterns emerge during angiography. Conventionally, drusen that
stain readily are taken to be 'hydrophilic', whereas those that do
not are 'hydrophobic'. Hydrophilic drusen are more
proteinaceous and are associated with an increased risk of
Fig. 16.3 Drusen come in various patterns, shapes and sizes with variable amounts of RPE change. Some patients develop widespread
drusen throughout the posterior pole.
AGE-RELATED MACULAR DEGENERATION
choroidal neovascularization; hydrophobic drusen have incr:eased
lipid and are more associated with PED. Other factors, such as
drusen size and extracellular matrix characteristics probably
influence staining too. However, it is the extent of RPE atrophy
seen as window defects (see Ch. 13) on angiography or as
blackness on autofluorescence imaging- rather than drusen-
that better reflects visual loss.
RETINAL DEGENERATIONS AND DYSTROPHIES

sparse staining
w ith fluorescein

Fig. 16.4 The drusen in this patient's macular area are relatively
hydrophobic, failing to stain as angiography progresses.

Fig. 16.5 This patient has more hydrophilic drusen. Note the submacular hyperfluorescence, which probably denotes early occult
choroidal neovascularization.
 AGE-RELATED MACULAR DEGENERATION

Fig. 16.6 Calcific drusen have a flat, glistening, white and

refractile appearance (left). These eyes tend to lose vision from
RPE atrophy rather than neovascularization, as seen in the more
gross example (right) .

confluent
drusen

Fig. 16.7 This patient has a large area of confluent drusen under
the macula. Such patients have a considerable risk of developing
choroidal neovascular lesions.
518 RETINAL DEGENERATIONS AND DYSTROPHIES

>--,.----f--7-+--tl area of central atrophy

RPE atrophy and

L~~-~Ss=;;i;l;;::::::z~J hyperplasia

Fig. 16.8 The degree of RPE atrophy varies considerably. This patient has small, sparse drusen, subretinal pigmentation from RPE
hyperplasia and a central-paracentral RPE defect, accounting for an acuity of 20/100 and a paracentral scotoma.

scleral staining

Fig. 16.9 Central areolar choroidal atrophy can be dominantly inherited but it is also a phenotypic variant of AMD in which there is a
sharp circumscribed demarcation line between normal and abnormal retina with central atrophy of the choriocapillaris, RPE and
photoreceptors revealing large choroidal vessels in the base (left). These lesions start in the macular area and gradually increase in extent
over time with severe loss of visual acuity. Drusen are not normally seen. (right) Angiogram of the same patient shows the large window
defect due to loss of the RPE and choriocapillaris. Large choroidal vessels are seen in the base and fill normally. Note the relative
hyperfluorescence of the rim of the lesion from scleral staining (see Ch. 13).
 AGE-RELATED MACULAR DEGENERATION

RETINAL PIGMENT EPITHELIAL DETACHMENT

As part of the degenerative process, fluid may collect between the
RPE and Bruch's membrane to induce a PED in the posterior
pole. This is seen clinically as a well demarcated, localized
elevation in the macular area that can be distinguished from
central serous retinopathy by its ·rather more solid and better
defined appearance. PEDs vary from 0.5 to 2 or 3 disc diameters
in size. Fluorescein angiography confirms the diagnosis by
showing a steadily increasing diffuse and even pattern of leakage.
Marked, well defined pooling is seen in the later stages. Uneven
intensity or focal hyperfluorescence indicates associated
subretinal neovascularization. PEDs are thought to b(saused by)
hydrophobic drusen material being deposited in Bruch's
membrane. This restricts fluid outflow into choroid by RPE cell
'pumping', so that fluid accumulates and cleaves the RPE off
Bruch's membrane.
In younger patients, the visual prognosis is relatively good and
no treatment is indicated; the detachment may persist for many
years without vision being affected significantly. In elderly
patients controlled trials have not shown any benefit from argon
laser photocoagulation and the effect of in photodynamic therapy
has not yet been studied. The condition is thus best left untreated
in all patients. Visual acuity may suddenly be lost if the detachep
RPE tears, resulting in the pathological event known as a
pigment epithelial tear or 'rip-off' syndrome. Tears may flap back
under themselves and sometimes cause simultaneous
haemorrhage. In some patients, especially those of Oriental or
African Caribbean descent, the differential diagnosis of
idiopathic polypoidal choriovasculopathy (IPCV) should also be
considered.

Fig. 16.10 Colour photograph

showing the well circumscribed
elevation of the macula, which has
a more prominent and thicker
appearance than that seen with
pigment central serous retinopathy (see
epith eIiaI t----:=''-;--+-.:.-. Fig. 16.38). In elderly patients
detachment other signs of macular
degeneration such as drusen,
pigmentation and atrophy are ·
frequently seen . Any surrounding
lipid exudate or haemorrhage
strongly suggests choroidal
neovascularizatiori. within the
lesion.

Fig. 16.11 The fluorescein

angiogram shows early diffuse
leakage which increases in
intensity as the run progresses
site of retina l
but remains localized to the
pigment 1-----..,+*+--
epithelial area of the lesion. Other
detachment degenerative changes in the
RPE are often seen.
20 RETINAL DEGENERATIONS AND DYSTROPHIES

Fig. 16.12 Elderly patients may have an underlying neovascular membrane, which is indicated by any unevenness of staining or
hyperfluorescence within the lesion.

Fig. 16.13 Excessive tension within the PED causes it to rip and fold
back on itself. This is often associated with haemorrhage into the lesion
and acute loss of acuity in the eye. Characteristically RPE rips show a
dark area where the RPE has folded back on itself separated by a straight
line from the area of denuded RPE . ·-':------"----\j exposed Bruch's membrane
By courtesy of Ms H Jackson. \~'-'-.,..-.,-;---fl straig ht edge of RPE rip

t...~-A'=::-+1 fold ed RPE

CHOROIDAL NEOVASCULAR MEMBRANES

Disciform degeneration of the macula is an old name derived
from the elevated mass of fibrosis and exudate that is seen
replacing the macula in the terminal stages of the disease. The
earliest pathological changes are rupture of Bruch's membrane
with penetration of a neovascular membrane derived from the
choriocapillaris. This invades drusen material and the subretinal
pigment epithelial and subretinal spaces. The process occurs in
the posterior pole of the eye, either under the macula, in the
paramacular area, or occasionally adjacent to the optic disc.
Similar lesions in the equatorial or peripheral retina can
occasionally occur in diseases such as pars planitis or retinitis
pigmentosa. In common with neovascular tissue elsewhere, these
vessels bleed and leak, producing subretinal exudate and fibrosis
with consequent disruption of the macular anatomy and
destruction of central vision.
While CNV is usually associated with AMD it is also the end-
result of a group of diverse conditions that appear to have in
common the ability to affect the posterior pole and damage
Bruch's membrane. The stimulus for the neovascular process is
thought to be the release of neovascular factors such as vascular
endothelial growth factor (VEGF) from the RPE, induced by
metabolic changes and hypoxia from thickening of Bruch's
membrane with age. This is modulated by a complex interaction
of other stimulatory factors and inhibitory factors such as
pigment epithelium-derived factor (PEDF) in a way anaJogous w
that seen with retinal neovascularization.
 AGE-RELATED MACULAR DEGENERATioN

Neovascular
r-1- -+-- - - mem brane under
outer seg ments

Neovascular
--..:,_7'_.-§-------1"~-- membrane
under RPE

' - - - - - - - - - - - Ruptu re of Bruch's

membrane

Fig. 16.14 CNV can grow between Bruch's membrane and the RPE (type 1) or in the subretinal space between the RPE and
photoreceptors (type 2); combinations of these occur as well. The appearance of CNV on angiography depends on the amount of
haemorrhage, pigment hyperplasia and RPE atrophy. Based on FFA findings, choroidal neovascular membranes (CNV) are divided into
classical and occult forms. Classical CNV is defined as well demarcated areas of hyperfluorescence that can be seen in the early phase of
fluorescein angiography with progressive leakage of dye obscuring the boundaries of the CNV as angiography progresses; these may
correspond to type 2 membranes. Occult CNV is either a fibrovascular PED with areas of irregular elevation of RPE producing an area of
stippled hyperfluorescence as the angiogram progresses or late leakage from an undetermined source; these may correspond to type 1
membranes. An alternative explanation of the different angiographic appearances is that a classical CNV represents a type 1 membrane
with overlying RPE atrophy. Further clinical pathological studies are needed.

inner ganglion 1----:;:;=::::;;~~;::::;:::;::::::::;::-1 gl iosed and

nucl ear layer cells remnants of disorgani zed
r-:::::=:::=::==F==='====::p- patchy RPE neuroretina retin a
loss of atrophy
photo recepto rs
normal RPE pigment
photo receptors

Bruch's choroid
' - -'--'--_L_L__ _ _ _ _ __ _ blood vesse ls
membrane

Fig. 16.15 Serial sections of eyes with drusen have shown that neovascularization of drusen in the posterior pole is not uncommon and
that only a minority of these lesions progress to a clinically apparent CNV. Pathology of end-stage disciform macular degeneration shows a
layer of vascularized fibrous tissue replacing the photoreceptors (left). In a gross example (right) the retina is completely destroyed by an
elevated mass of vascularized fibroglial tissue.
 NERATIONS AND DYSTROPHIES

masking by haemorrhage

Fig. 16.16 The typical classical CNV lesion, no matter what the aetiology, consists of subretinal elevation either beneath or adjacent to
the fovea. Recent lesions often have a pale, raised appearance with variable amounts of lipid or haemorrhage. A subretinal haemorrhage in
the macular area should always raise the suspicion of a neovascular cause. Presenting symptoms are either metamorphopsia or blurring of
vision, depending on the size and site of the lesion. Early-phase fluorescein angiography of the same lesion shows the classical appearance
of a neovascular complex lying beneath the retina which, because it is derived from the choroid, fills early in angiography. Individual vessels
in the neovascular membrane may be identified in the earliest stages as a net-like membrane. In common with other neovascular tissue, the
capillaries in the neovascular membrane have loose endothelial cell junctions and in late stages the membrane shows intense leakage into
the adjacent retina, blurring the membrane . These lesions are amenable to photodynamic treatment.

haemorrhage
and subretinal
fluid

Fig. 16.17 Occult CNV membranes are more common than clas sical lesions. This patient presented with distortion and blurring of vision
to 20/80. Angiography shows an irregular leakage in the lesion, staining intensively in the later phases. These lesions d o not benefit as much
from photodynamic treatment .
 subretinal haemorrhage maski ng by haemorrhage

Fig. 16.18 CNV is often associated with subretinal haemorrhage which may produce a sudden drop in visual acuity causing the patient
to present. In this situation haemorrhage may mask the true extent of the membrane and fluorescein angiography should be postponed
until sufficient haemorrhage has been absorbed for visualization. ICG angiography may help in these circumstances as it reveals the extent
of the membrane despite the overlying haemorrhage.

subretinal hard exudate ext ensive occult CNV

Fig. 16.19 An exudative reaction may occur around a disciform lesion producing a circinate subretinal exudate with central subretinal
neovascularization. In some patients exudates are the major feature of the fundus appearance.
 AND DYSTROPHIES

Fig. 16.20 CNV may resolve leaving subretinal fibrosis with some improvement in vision (left) or progress to leave massive disciform
subretinal fibrosis (middle) or RPE scarring (right).

OTHER CAUSES OF CHOROIDAL NEOVASCULAR MEMBRANES

Neovascularization through Bruch's membrane occurs in a wide range of fundus disorders that have in common the ability to disrupt
or damage the RPE or Bruch's membrane in the macular area.

ANGIOID STREAKS

Fig. 16.22 Pseudoxanthoma elasticum is a recessively inherited

disorder affecting connective tissue elastic fibres. Patients have
cutaneous, ocular and vascular manifestations and suffer premature
hypertension, atheroma, cardiac valve disorders and
Fig. 16.21 Angioid streaks are splits in Bruch's membrane. They
gastrointestinal haemorrhage. This patient has the characteristic
appear as linear fractures extending from the optic disc and
'chicken skin' changes on her neck, which she disguises by wearing
ramifying towards the periphery mimicking retinal blood vessels.
a polo-neck shirt.
They are usually reddish brown but may show degenerative
pigmentary changes. Their appearance on angiography depends on
the degree of associated pigmentary disturbance and RPE loss. The
majority of streaks are hyperfluorescent, although early in the run
they may mask background choroidal fluon:-scence. Subretinal
neovascularization in the papillomacular region or alongside the
optic disc is a frequent complication. Angioid streaks occur as an
isolated ocular finding or with systemic associations which include
elastic tissue disorders such as pseudoxanthoma elasticum and \
Ehlers-Danlos syndrome.
 drusen of
th e disc

subreti nal
f ibrosis

angioid
streaks L_-=~-"":::::::__ _j

Fig. 16.23 Remarkably conspicuous angioid streaks radiate from

the patient's optic disc which also has the well recognized
association of pronounced optic disc drusen. Juxtapapillary and
subretinal fibrosis from neovascularization can be seen underlying
the macula. This patient has widespread RPE changes within and
adjacent to areas of subretinal neovascularization; visual prognosis
is poor.
By courtesy Mr R K Blach.

normal

peau d'orange change

Fig. 16.24 In patients with pseudoxanthoma elasticum, Bruch's

membrane and the RPE may also be altered, giving the fundus a
slightly mottled, yellowish and refractile appearance known as
'peau d'orange' . This is most noticeable in the p osterior pole and
contrasts with the normal appearing periphery.

CHOROIDAL RUPTURE

'Choroidal rupture' is caused by severe blunt injury to the eye but the appearance is in fact due to rupture of Bruch's membrane (see
Ch. 14). CNV can develop some time later in lesions extending into the macular area .

subretinal
concentric bands
fluid
of 'choroidal' rupture

'choroidal'
..J..I..;.,y---; rupture

disciform lesion

Fig. 16.25 In this patient, rupture is seen as a typical chorioretinal scar lying concentric to the optic disc with fresh, pale, submacular
fluid that has caused recent onset of blurring and distorted vision . Fluorescein angiography demonstrates the extent of the RPE and
choriocapillaris disruption with a subfoveal CNV. Photodynamic therapy has a potential role in the managment of these patients.
 PHIES

OCULAR HISTOPLASMOSIS AND PUNCTATE INNER CHOROIDOPATHY

The ocular histoplasmosis syndrome describes a pattern of appearances are seen in European patients in the absence of
fundus abnormalities related to endemic Histoplasma capsulatum histoplasmosis infection and are known as punctate inner
infection in the North American Midwest. Similar fundal choroidopathy (PI C).

punctate RPE atrophy

linear patterns
of peripheral
RPE atrophy

Fig. 16.26 The typical appearance of the fundus comprises the triad of atrophic
changes around the optic disc, localized punched-out areas of pigment epitheiial
atrophy in the posterior pole and atrophic, usually linear, RPE lesions in the
equatorial retina (bottom left) . Atrophic changes in the macular region carry a
substantial risk of developing CNV, typically in early middle age.
PERIPAPILLARY CNV

Choroidal neovascularization may develop adjacent to the optic disc, either spontaneously or in association with disc abnormalities
such as tilting or chronic pathological disc swelling or drusen of the disc (see C h . 17).

early filling
of neovascu lar
membrane

subretinal fluid
and RPE atrophy

Fig. 16.27 Lesions extending into the papillomacular region cause a profound loss of central vision but more eccentric membranes do
not necessarily affect vision . This patient has chronic papilloedema with an adjacent CNV and subretinal fluid.

RUBELLA

Fig. 16.28 Congenital rubella can produce large patches of RPE

change. If these affect the macula there is a high risk of CNV in
middle age .
 ERATIONS AND DYSTROPHIES

MYOPIC MACUlAR DEGENERATION

mottling of RPE
!:---r'-"7""'----1 and fine
'lacquer' cracks

Fig. 16.29 High myopes have an increased risk of developing atrophic macular degeneration- seen as chorioretinal thinning or atrophy,
posterior staphylomata and splits in Bruch's membrane termed 'lacquer' cracks- and also peripheral lattice degeneration. This patient
shows a large myopic crescent on the temporal side of the optic disc. Retinal vessels are pulled straight as they enter the enlarged posterior
pole. In the macula there is patchy pigmentary disturbance and fine cracks in Bruch's membrane.

choroidal vessels
seen through
thin RPE

Fig. 16.30 This patient shows marked myopic chorioretinal atrophy in both eyes with exposed sclera at each posterior pole.
Acuity was reduced to HM in the right eye and CF in the left. There is gross chorioretinal atrophy of the macula in the right eye with
exposed bare sclera.
 optic nerve

posterior pole
staphyloma

Fig. 16.31 Magnetic resonance imaging demonstrates a large posterior pole staphyloma
extending posteriorly to the optic disc in the right eye.

Fig. 16.32 High myopes have an increased risk of developing CNV in early adulthood, usually presenting with a fairly small localized
haemorrhage (Foster-Fuchs' spot). Extensive exudate or serous detachment does not occur and the condition resolves to leave a small
pigmented scar. Visual recovery is much better than with other types of CNV lesion. Photodynamic therapy may improve the prognosis.

TREATMENT OF AGE-RELATED CHOROIDAL NEOVASCULARIZATION

The only clinically proven treatment for choroidal
neovascularization is the destruction of extrafoveal CNVs by
argon laser photo ablation and of classical subfoveal membranes
by photodynamic treatment. At present, however, a number of
clinical trials are being conducted to assess other modalities such
as anti-VEGF aptamers, PEDF gene constructs and anti-
angiogenic steroids and in future combinations of laser and
pharmacological treatment are likely to be used.
Thermal burns produced by argon laser will destroy choroidal
neovascularization and limit, to some extent, further retinal
destruction and visual loss. Lesions can be treated up to the edge
of the foveal avascular zone but care must be taken with
juxtafoveal lesions as damage from the burn can spread outside
the treated area. A problem with lesions adjacent to the fovea is
that the macular yellow luteal pigment absorbs energy which may
then thermally injure the overlying neuroretina and enlarge the
scotoma. If light is restricted to the green bands of the argon
spectrum the laser energy is taken up by blood and the RPE,
sparing the neuroretina; long-wavelength krypton or diode laser
energy is also taken up by RPE and choroidal pigment but not by
the luteal pigment and so can be useful in this situation.
Subfoveal CNV cannot be treated by thermal laser without
destroying central vision. Although successful treatment
improves the short-term visual prognosis this is not sustained in
the long term and studies show that after 3-4 years vision has
fallen in 50- 60 per cent of patients from further macular
degeneration.
With photodynamic therapy a photosensitizing dye
(verteporfin) is given intravenously and is taken up by the
vascular endothelium. The lesion is then exposed to 689-nrn
light; the dye is excited and releases singlet oxygen which
damages the endothelium and thromboses the membrane.
Although multiple treatments are required clinical studies have
shown that this treatment can slow visual loss in eyes with
predominantly classical subfoveal CNV. The parameters of PDT
treatment are still being evaluated. Classic membranes appear to
have the best response but some improvement can be seen with
lesion~ that have less than 50% classic changes or even with small
recent occult lesions. PDT is also being used for treatment of
other neovascular lesions such as those associated with angioid
streaks or myopic CNV.

Fig. 16.33 This patient has a

fresh parafoveal CNV with
serous detachment extending
into the fovea and an acuity of
20/40. Fluorescein angiography
is essential prior to treatment to
assess the full extent of the
membrane. The most important
images are taken in the earliest
inten se leakage arterial phases of angiography,
from neovascular f-¥~j.._.,.~4 before leakage of dye into the
retina elevated f-+1-f--~
by subretinal fluid
membrane retina has obscured the fine
atrophic RPE vascular detail. Fixation must be
changes identified.

fresh heavy la ser

burns ob literating
neovascula r 1-h~~.J-----1,.
membrane

Fig. 16.34 Lesions must be treated heavily and completely; partial or

incomplete photocoagulation carries the risk of provoking a rapid extension of the
membrane. Immediately after treatment by argon laser an opaque reaction can be
seen deep in the outer retina. The more intense parafoveal burn is due to energy
absorption by luteal pigment. Visual acuity fell to 20/80 immediately after
treatment.
 TREATMENT

Fig. 16.35 Four weeks' later a pigmented scar is forming in the

region of the burns. Fluorescein angiography shows complete
obliteration of the membrane . Visual acuity improved to 20/30 with
a small paramacular scotoma which the patient easily compensated
for. Risk of recurrence in eyes with thermally treated CNV is
approximately 10% a year; the fellow eye carries a similar risk of
developing CNV formation .

residual membrane

Fig. 16.36 This patient has a subfoveal classic CNV. Following photodynamic therapy the membrane has regressed. Further treatment is
indicated if there is residual haemorrhage, hard exudate or subretinal fluid and fluorescein leakage from the membrane 8- 10 weeks later.
-.u:: I ll'fi-\L UI:UI:I'fi::I\1-\IIUI'f::l 1-\l'fU lJ T ::II 1\Ut'Mit::l

IDIOPATHIC POLYPOIDAL CHORIORETINOPATHY (IPCV)

IPCV was first described in middle-aged black hypertensive
women but is now recognized in Asians and older Caucasians.
The primary abnormality appears to be localized aneurysmal
inbulging of inner choroidal vessels through Bruch's membrane,
seen clinically as p olyp-like lesions. The lesions leak, causing
multiple, recurrent, serosanguinous RPE detachments and may
bleed subretinally, sometimes breaking through into the vitreous.
Characteristically, drusen, retinal vascular disease and uveitis are
absent. Lesions tend to be p eripapillary but may be seen in the
macular region. Patients present with visual loss; in some this is
permanent whereas in others good vision is spontaneously
regained despite retinal scarring. The natural history is not fully
known. ICG angiography helps in diagnosis and treatment of the
lesion with laser photoablation or PDT appears to be more
effective than in eyes with AMD and choroidal
n eovascularization.

focal retinal
elevation (;f"1,r:;----:::::~=~;z--~L__-11C G shows choroi
vascular lesions

Fig. 16.37 This black patient has subretinal haemorrhage and hard exudates adjacent to the disc. Fluorescein angiography shows deep
subretinalleakage and ICG angiography shows two foci of polypoid change underlying these which probably represent herniation of
choroidal vessels through Bruch's m embrane.

CENTRAL SEROUS RETINOPATHY

This condition is seen most commonly in patients between the
ages of 20 and 40 years with a male : female ratio of 8 : 1.
Corticosteroid treatment and stress are well recognized risk
factors. A serous retinal detachment develops at the macula in
association with a focal leak through the RPE; fluid passes from
the choriocapillaris to the subretinal space where it accumulates.
The site of leakage is usually above the horizontal m eridian and
outside the avascular central zone.
Patients present with micropsia and slightly blurred or
distorted vision, typically improved by a + 1D lens. The
photostress test is positive. The condition usually has a self-
limiting course of several months; recovery can be accelerated by
laser photocoagulation of the leak although the final visual result
is unchanged and the risk of developing choroidal
neovascularization may be increased . Visual recovery is usually
good but some, especially older patients, do less well. Some
patients develop recurrent or chronic disease.
 CENTRAL SEROUS RETINOPATHY

Fig. 16.38 The typical fundus appearance is of a thin translucent blister underlying the macula. This may be difficult to see by direct
ophthalmoscopy and is more readily visible by biomicroscopy. The diagram illustrates the small break in the RPE and serous retinal
detachment elevating the macula.

upper border of
serous detachment

smoke stack

Fig. 16.39 Fluorescein angiography in the early stages of the

disease shows a focal defect in the RPE with a typical 'smoke
stack' pattern of leakage. The leakage appears as a small
hyperfluorescent spot at the site of the breech in the RPE and
flows upwards in a column, influenced, presumably, by local
convection. When the dye reaches the upper margin of the
detachment it spreads laterally along its circumference and
eventually fills the whole detachment.

serous detachmen1
seen with
- red-free
photography
serous
detachment

Fig. 16.40 In the established case the area of RPE defect can
often be seen as a pale spot. Red-free photography shows the
elevated retina more clearly.
4 RETINAL DEGENERATIONS AND DYSTROPHIES
INHERITED RETINAL DYSTROPHIES
CLASSIFICATION OF INHERITED RETINAL DISEASE
Clinically inherited retinal dystrophies are classified by natural
history (stationary or progressive), mode of inheritance
(autosomal dominant, autosomal recessive, X-linked recessive,
mitochondrial or, less commonly, multiallelic inheritance) and
putative site of dysfunction within the retina. The latter may be
inferred from the results of psychophysical and
electrophysiological testing (see Ch. 1) and the various methods
of fundus imaging such as fluorescein angiography,
autofluorescence imaging and optical coherence tomography.
MANAGEMENT OF RETINAL DYSTROPHIES
Inherited retinal disorders are not amenable to any form of
treatment, except in a few rare disorders (e.g.
abetalipoproteinaemia, Refsum disease, and gyrate atrophy)
where a metabolic defect is known. However, all patients and
their families benefit from genetic counselling, educational and
occupational advice and supportive measures such as visual
rehabilitation and the treatment of concurrent ocular problems
(e.g. myopia and cataracts). Advances in molecular biology have
led to the identification of many of the causative genetic
mutations and it is likely that over the next few years the
Fig. 16.41 As the lesion
becomes chronic the leaking
point loses its 'smoke stack'
appearance and shows as a
localized diffusion of dye from
the central leaking point
known as an 'ink blot'. This
may be due to increasing
viscosity of the subretinal
fluid limiting diffusion of the
dye.
This approach has limitations and a more robust classification
which more accurately reflects disease pathogenesis awaits the
identification of the many genetic mutations associated with
retinal disease. More than 90 genes and 140 loci associated with
inherited retinal degeneration have now been identified with
many more yet to be discovered. At present, routine molecular
diagnostic testing is available for only a few disorders but the
numbers will increase as advances are made in the technology of
molecular genetic analysis.
underlying molecular pathology of most disorders will be known
which should offer new therapeutic prospects. Treatment
strategies aimed at prolonging photoreceptor survival with
exogenous growth factors, stem cells, gene therapy and RPE or
photoreceptor transplantation are currently being investigated in
animal models and some will be the subject of therapeutic trials
in the near future. Another approach is the development of an
artificial retina that would utilize residual ganglion cell function
in patients with complete loss of photoreceptor function.

INHERITED CENTRAL RECEPTOR {MACULAR) DYSTROPHIES
The hereditary macular dystrophies (central receptor
dystrophies) comprise a heterogeneous group of disorders
characterized by bilateral central visual loss, defects in colour
vision and the finding of generally symmetrical macular
abnormalities on ophthalmoscopy. The age of onset is variable,
but most present in the first two decades of life. A number of
different genes and chromosomal loci causing macular dystrophy
AUTOSOMAL RECESSIVE INHERITANCE
Stargardt disease and fundus flavimaculatus (FFM}
Autosomal recessive Stargardt macular dystrophy (STGD) is the
most common inherited macular dystrophy with a prevalence of
1 in 10 000. Most patients present with central visual loss in their
early teens but STGD may also present in adult life when the
visual loss is usually milder. The electrophysiological
abnormalities detected are variable. An abnormal electro-
oculogram (EOG), suggestive of RPE dysfunction is a common
finding. The pattern electroretinogram (PERG) and focal ERG
are usually abolished or markedly reduced indicating macular
dysfunction. The full-field ERG may be normal at diagnosis or
over time may show changes consistent with widespread retinal
dysfunction. Patients who show an abnormal full-field ERG at
diagnosis have a poorer long-term visual prognosis.
The locus for STGD-FFM has been mapped to chromosome
lp and the causative gene, ABCA4, characterized. Mutations in
ABCA4 have also been implicated in other disorders, including
retinitis pigmentosa (RP) and cone- rod dystrophy (CORD). It is
currently believed that homozygous null mutations cause the
INHERITED CENTRAL RECEPTOR (MACULAR) DYSTROPHIES
have now been identified with autosomal dominant (AD),
autosomal recessive (AR), X-linked (XL) recessive and
mitochondrial inheritance having been reported. Macular
abnormalities may also be seen in a variety of inherited
multisystem disorders which are outside the scope of this
chapter;
most severe phenotype of autosomal recessive RP; combinations
of a null mutation with a moderate missense mutation result in
autosomal recessive CORD; and combinations of null/mild
missense or two moderate missense mutations cause
STGD- FFM. ABCA4 encodes a transmembrane rim protein
located in the discs of rod and foveal cone outer segments that is
involved in ATP-dependent transport of retinoids (intermediates
in the vitamin A recycling pathway) from photoreceptor to RPE.
Failure of this transport results in deposition of a major
lipofuscin fluorophore, A2E (N-retinylidene-N-retinyl-
ethanolamine), in the RPE. It is thought that this accumulation
may be deleterious to the RPE with consequent secondary
photoreceptor degeneration. Growing evidence from in vitro
studies and mouse models suggests that the deleterious effects of
A2E can be alleviated by a variety of interventions that either
antagonize the toxic effects of A2E or inhibit its biosynthesis.
no macular atrophy
Fig. 16.42 The term fundus flavimaculatus (FFM) is often used
to describe a phenotype in which there are multiple white flecks
without significant macular atrophy. It appears that STGD and
FFM are caused by mutations in the same gene and both patt~rns
may be seen within the same family.
 macular atrophy

paramacular subretinal flecks

Fig. 16.43 Typically there is macular atrophy with white flecks at the level of the RPE at the posterior pole. The flecks may be fish tail-
shaped (pisciform), round, oval or semilunar. The area of macular atrophy may in the early stages have a 'beaten bronze' appearance.

Fig. 16.44 Fluorescein angiography classically reveals a dark or masked choroid. The reduced visualization of the choroidal circulation in
the early phase of fundus fluorescein angiography (FFA) is believed to be secondary to excess lipofuscin accumulation in the RPE ~
obscuring the fluorescence emanating from choroidal capillaries. The retinal flecks appear hypofluorescent on FFA early in their evolution
but at a later stage they appear hyperfluorescent as a result of RPE atrophy.

AUTOSOMAL DOMINANT INHERITANCE
Autosomal dominant Stargardt-like macular dystrophy
The clinical appearance of autosomal dominant Stargardt-like
macular dystrophy (ADSTGD) is so similar to the common
autosomal recessive form of the disorder that it is difficult to
differentiate between them by fundus examination alone .
However, in ADSTGD affected individuals have a milder
phenotype with relatively good functional vision, minimal colour
vision defects and no significant EOG or ERG abnormalities.
The 'dark choroid' sign on fluorescein angiography that is typical
in the recessive form (but not pathognomonic) is uncommon in
Best disease {vitelliform macular dystrophy)
Best disease is dominantly inherited and characterized clinically
by the classical feature of a round or oval yellow subretinal
macular deposit. Full-field ERG is normal but the EOG shows a
very reduced or absent light rise indicating that there is
widespread dysfunction of the RPE. The visual prognosis in Best
disease is surprisingly good with most patients retaining reading
vision into the fifth decade of life or beyond. The disease shows
very variable expressivity although the majority of individuals
who carry mutations in the VMD2 gene have an abnormal EOG;
this is extremely useful in assigning disease status when
counselling in Best disease . Family members who carry a
INHERITED CENTRAL RECEPTOR (MACULAR) DYSTROPHIES
Fig. 16.45 Progressive macular atrophy can be seen in this
patient. The photographs were taken 6 years apart.
the dominant form of the disorder. Two chromosomal loci have
been identified, 6q14 (STGD3) and 4p (STGD4) . Mutations in
the gene ELOVL4 have been associated with STGD3 and other
macular dystrophy phenotypes including pattern dystrophy. This
gene is expressed in the rod and cone photoreceptor inner
segments with the protein product believed to be involved in
retinal fatty acid metabolism. A mutation in PROMJ , a gene
believed to play a role in photoreceptor outer segment disc
formation has been identified in STGD4.
mutation m the VMD2 gene and who have minimal macular
abnormality or a normal fundus appearance (but abnormal
EOG) in early adult life usually retain near-normal long-term
visual acuity. The protein product of VMD2, bestrophin, has
been localized to the basolateral plasma membrane of the RPE,
where it forms a component of a chloride channel. It has been
suggested that impaired fluid transport in the RPE secondary to
abnormal chloride conductance may lead to accumulation of
fluid and/or debris between the RPE and photoreceptors and
between the RPE and Bruch's membrane, leading to detachment
and secondary photoreceptor degeneration.
masking of
submacular cho roidal pattern
vitelliform f-~+--­
lesion
normal retinal
L..":'::-=;;:~~~~J vesse ls
Fig. 16.46 The phenotype has been classified into five stages.
Stage 0 (previtelliform) is characterized by a normal fundus
appearance in an asymptomatic gene carrier with an abnormal
EOG. In stage I, minor RPE changes are seen. The classical
vitelliform lesion (stage II) is characterized by the 'egg yolk'
macular lesion that masks the underlying choroidal fluorescence .
This appearance is usually seen during the first or second decades,
often associated with normal, or slightly reduced, visual acuity.
II RETINAL DEGENERATIONS AND DYSTROPHIES
.

Fig. 16.47 The 'egg yolk' begins to break up secondary to

resorption of the yellow material lying between the RPE and
sensory retina (stage Ila) with visual impairment usually being
noticeable at this stage.

elevated macula

pseudohypoyon

Fig. 16.48 Stage III (pseudohypoyon) is

seen when part of the lesion is resorbed,
leaving the appearance of a 'fluid level' at the
macula. The yellow material is completely
resorbed over time, leaving an area of RPE
atrophy (stage IVa) and often subretinal
fibrosis (IVb). Choroidal neovascularization is
an established complication leading to severe
visual loss (IVc) .

Adult vitelliform macular dystrophy

Adult vitelliform macular dystrophy (AVMD) is often confused EOG. Mutations in the peripherin/RDS gene on chromosome 6p
with Best disease although, as the name suggests, it has a later have been identified in approximately 20 per cent of patients with
onset, lacks the typical course through different stages of macular AVMD.
disease seen in classical Best disease and often has a normal

Pattern dystrophy
The pattern dystrophies are a group of inherited disorders of the
RPE characterized by bilateral symmetrical yellow-orange
deposits at the macula in various distributions, including
butterfly or reticular-like patterns, most likely representing
lipofuscin accumulation. They are often associated with a
relatively good visual prognosis although in some cases a slowly
progressive loss of central vision occurs secondary to atrophic
macula changes. The age at presentation is variable and is usually
between the second and fifth decades of life. Electrophysiological
increased =--..c.....,__
autofluorescence
Fig. 16.49 The typical clinical appearance is of bilateral, round
or oval, yellow, symmetrical, subretinal lesions, typically one-third
to one-half optic disc diameter in size. The autofluorescence image
shows increased autofluorescence corresponding to the macular
lesion suggesting that this is due to accumulated lipofuchsin.
By courtesy of Mr Andrew ~bster.
findings usually reveal abnormal EOG and pattern ERG with
normal full-field ERG. Mutations in the peripherin/RDS gene
have been identified in some patients but other genes remain to
be identified. The peripherin/RDS protein is a membrane-
associated glycoprotein restricted to photoreceptor outer
segment discs in a complex with ROMl. It may function as an
adhesion molecule involved in the stabilization and maintenance
of the compact arrangement of outer segment discs .
 atrophic changes

subretinal deposits

..,_._-~--'>-1 increased autofluorescence

of deposits

Fig. 16.50 This patient has bilateral orange-yellow deposits at

the macula in a reticular-like distribution associated with some
RPE atrophy in the left eye. Autofluoresence imaging suggests that
the deposits contain lipofuscin.
By courtesy of Mr Andrew I-%bster.

..
 INHERITED CENTRAL RECEPTOR {MACULAR) DYSTROPHIES

Doyne honeycomb retinal dystrophy (malattia Jeventinese; autosomal dominant drusen)

In this disorder small round yellow-white deposits under the
RPE begin to appear in early adult life characteristically
distributed at the macula and around the optic disc. Visual acuity
is maintained through the fifth decade but patients often become
legally blind by the seventh decade. Visual loss is usually due to
macular atrophy and less commonly from subretinal
neovascularization. A single mutation (arginine-345-to-
tryptophan) in the gene EFEMPJ on chromosome 2p has been
identified in the majority of patients. This is a widely expressed
gene predicted to encode an extracellular matrix glycoprotein. It
has been proposed that misfolding and aberrant accumulation of
this protein within RPE cells and between the RPE and Bruch's
membrane may be the underlying defect.

Fig. 16.51 The yellow-white drusen-like deposits classically appear to radiate like the spokes of a wheel from the macula and
characteristically surround the optic disc.

North Carolina macular dystrophy

North Carolina macular dystrophy (NCDRI) is an autosomal
dominant disorder that is characterized by a variable macular
phenotype and a nonprogressive natural history. EOG and ERG
are normal indicating that there is no generalized retinal
dysfunction. It has been described in various countries including
Europe and all cases have mapped to a locus on chromosome
6q 16. The identification of the gene responsible is keenly awaited
as this will help to improve our understanding of the
pathogenesis of drusen and subretinal neovascular membrane
(SRNVM).
RETINAL DEGENERATIONS AND DYSTROPHIES

subretinal fibrosis

atrophic RPE

subreti nal fibrosis

Fig. 16.52 Bilaterally symmetrical fundus appearances in MCDRl range from a few small (less than 50 Jlm) yellow drusen-like lesions in
the central macula (grade 1) to larger confluent lesions (grade 2) and macular colobomatous lesions (grade 3). Occasionally MCDRl is
complicated by SRNVM at the macula.

Sorsby fundus dystrophy

Sorsby fundus dystrophy (SFD) is a rare, autosomal dominant
macular dystrophy with onset of night-blindness in the third
decade and loss of central vision from macular atrophy or
SRNVM by the fifth decade. A tritan colour defect has been
suggested as an early sign. The tissue inhibitor of
metalloproteinase 3 (TIMP3 gene on chromosome 22q) is
implicated. An abnormal tertiary protein structure is thought to
alter TIMP3-mediated extracellular matrix turnover leading to
the thickening of Bruch's membrane and the widespread
accumulation of abnormal material beneath the RPE seen
histologically. High doses of oral vitamin A reverse the night-
blindness and suggest that retinal dysfunction may be due to a
reduction in the permeability of Bruch's membrane resulting in
defective vitamin A transport from the choriocapillaris to the
photoreceptors by accumulated extracellular debris beneath the
RPE. TIMP3 has also been shown to be a potent inhibitor of
angiogenesis which may account for the recognized complication
of choroidal neovascularization seen in SFD.

Fig. 16.53 This patient has widespread RPE atrophy and drusen with an island of RPE preserved centrally. The patient had acuities of
20/100 and 20/40 with a paracentral ring scotoma in each eye.
X-LINKED INHERITANCE
X-linked juvenile retinoschisis (XLRS)
XLRS is a vitreoretinal degeneration that presents either in a
male infant with nystagmus or, more commonly, in childhood
with mild loss of central vision. Full-field ERG typically reveals a
negative waveform with the a-wave larger in amplitude than the
b-wave indicating inner retinal dysfunction. Prognosis is good in
most affected males as long as retinal detachment or vitreous
haemorrhage does not occur. XLRS has been linked to Xp22.2
and mutations in the gene XLRSJ (also referred to as RSJ),
INHERITED CENTRAL RECEPTOR (MACULAR) DYSTROPHIES
which is expressed in photoreceptors and bipolar cells have been
identified. XLRS shows both intrafamilial and interfamilial
variability in the phenotype. XLRSJ encodes the protein
retinoschisin (RSl), which contains a highly conserved discoidin
domain implicated in cell- cell adhesion and cell- matrix
interactions, functions that correlate well with the observed
splitting of the retina in XLRS . Female carriers have a normal
fundus appearance and normal EOG and ERG.
44 RETINAL DEGENERATIONS AND DYSTR OPHIES
schi sis cav ity
Fig. 16.55 Peripheral retinal abnormalities including bilateral cavities, vascular closure, inner retinal sheen and pigmentary retinopathy
are seen in approximately 50 per cent of cases.
MITOCHONDRIAL INHERITANCE
Maternally inherited diabetes and deafness (MIDD)
MIDD is a subtype of diabetes mellitus that co-segregates with
an adenine-to-guanine trans1t10n at pos1t10n 3243 of
mitochondrial DNA (A3243G) in a transfer RNA leucine-
encoding region. Mitochondrial inheritance is matrilineal
because sperm do not contribute mitochondria to the zygote.
Both sexes can therefore be affected by MIDD but the disorder
Fig. 16.54 The characteristic fundus abnormality is a cystic
spoke wheel-like maculopathy (foveal schisis) in virtually all
affected males.
subretinal fibrotic band
is passed on only by affected mothers. Prognosis is generally
good with the majority of patients retaining very good central
vision. As the prevalence of macular dystrophy in MIDD is high,
the association of a macular dystrophy with diabetes should
always raise the possibility of screening for a _?litochondrial DNA
mutation.
 .

paramacular atrophy

choroidal vessels

Fig. 16.56 A bilateral macular dystrophy is present in the majority of patients with MIDD characterized by RPE atrophy that can
surround the macula or be more extensive and encompass the optic disc. In advanced cases areas RPE atrophy encircling the macula may
coalesce and involve the fovea at a late stage.

INHERITED RETINAL DYSTROPHIES WITH GENERALIZED RETINAL INVOLVEMENT

STATIONARY RETINAL DYSTROPHIES

Most dystrophies are progressive but others, notably stationary recognized: congenital stationary night-blindness (CSNB),
night-blindness and some cone dysfunction syndromes, are fundus albipunctatus and Oguchi disease.
stationary. Three forms of stationary night-blindness are

Congenital stationary night-blindness

CSNB is characterized by night-blindness, variable visual loss
and a normal fundus examination. It may be inherited as an
autosomal dominant (AD), autosomal recessive (AR) or X-
linked (XL) disorder. Patients with AD CSNB usually present
with symptomatic night-blindness and have normal visual acuity
but those with XL and AR CSNB usually present in infancy with
nystagmus, strabismus and reduced vision. Visual acuity is
usually normal in the AD form. In XL and AR CSNB there is
usually reduced central vision, moderate to high myopia,
nystagmus, strabismus and, in some cases, paradoxical pupil
responses (pupillary dilatation to bright light). Fundus
examination is usually normal but some patients have pale or
tilted optic discs.
XL CSNB is further subdivided into complete and incomplete
forms. Patients with complete CSNB are invariably myopic and
have more pronounced night-blindness. Both complete and
incomplete CSNB show a negative type of ERG in that the
photoreceptor derived a-wave in the maximal response is normal
but there is selective reduction in the inner nuclear derived b-
wave so that it is smaller than the a-wave. In complete CSNB
there is no detectable rod-specific ERG. Cone ERGs show subtle
abnormalities now known to reflect ON pathway dysfunction
(see Ch. 1). In contrast there is a detectable rod-specific ERG in
incomplete CSNB and cone ERGs are much more abnormal
than in complete CSNB, reflecting involvement of both ON and
OFF pathways.
 Mutations in genes encoding three components of the rod
phototransduction cascade have been reported in association
with the dominant form of CSNB; namely rhodopsin, the a-
subunit of rod transducin and the rod cyclic guanosine
monophosphate (cGMP) phosphodiesterase ~-subunit. Two
genes (CACNA 1F and NYX) have now been implicated in XL
CSNB. Incomplete CSNB is associated with mutation in
CACNAJF, which encodes the retina-specific a 1F-subunit of the
voltage-gated L-type calcium channel expressed in the outer
nuclear layer, inner nuclear layer and ganglion cell layer. The loss
of functional channels impairs the calcium flux into rod and cone
photoreceptors required to sustain tonic neurotransmitter release
from presynaptic terminals. This may result in an inability to
maintain the normal transmembrane potential of bipolar cells,
such that the retina remains in a partially light-stimulated state,
unable to respond to changes in light levels. Complete CSNB is
associated with mutation in NYX, the gene encoding the leucine-
rich proteoglycan, nyctalopin. It has been suggested that
nyctalopin plays a role in the development and function of the
ON pathway within the retina.
Oguchi disease
Oguchi disease is a rare autosomal recessive form of stationary
night-blindness in which there is a peculiar greyish or green-
yellow discoloration of the fundus that reverts to normal on
prolonged dark adaptation (Mizuo- Nakamura phenomenon).
Although most cases have been reported from Japan, Oguchi
disease may occur in other races including Europeans and
African Americans. Visual acuity is usually normal or only mildly
reduced and photopic visual fields and colour vision are normal.
Most patients with Oguchi disease have a negative maximal
ERG, confirming the site of dysfunction to be post-
phototransduction, as in XL CSNB. In direct contrast to fundus
albipunctatus the ERG remains abnormal even after prolonged
dark adaptation. Mutations have been identified in two rod
phototransduction proteins, arrestin and rhodopsin kinase,
which are both involved in terminating activation of the cascade
and thereby restoring photoreceptor sensitivity after exposure to
light: In Oguchi disease the rods therefore behave as if they are
light adapted and thus unresponsive to light at low levels of
illumination.
Fundus albipunctatus
Patients with this autosomal recessive form of stationary night-
blindness usually have normal visual acuity; the condition is
nonprogressive in the majority of affected individuals. The rod-
specific ERG is undetectable under standard conditions but
becomes normal following prolonged dark adaptation, in
contrast to Oguchi disease. Mutations in RDH5 the gene
encoding 11-cis-retinol dehydrogenase, a component of the
visual cycle, have been identified in fundus albipunctatus. The
function of the protein product of RDH5 is consistent with the
delay in the regeneration of photopigments characteristic of the
disorder.

normal macula

Fig. 16.57 There is a characteristic fundus appearance with multiple white

dots scattered throughout the retina at the level of the RPE. The dots are most
numerous in the mid-periphery and are usually absent at the macula. Patients
present either with night-blindness or because the abnormal retinal appearance
white dots in radial pattern
is noted on routine fundoscopy.

STATIONARY CONE DISORDERS (CONE DYSFUNCTION SYNDROMES)
Achromatopsia
Achromatopsia refers to a genetically heterogeneous group of
stationary retinal disorders in which there is an absence of
functioning cones in the retina. These disorders are characterized
by reduced central vision, poor colour vision, photophobia and a
normal fundus examination and may occur in complete (typical)
and incomplete (atypical) forms.
Complete achromatopsia (rod monochromatism), a rare
disorder with an incidence of approximately one in 30 000, is
inherited as an autosomal recessive trait and results in impaired
vision and complete colour blindness. The usual presentation is
with reduced vision (20/ 120- 20/200), nystagmus and marked
photophobia in infancy. Vision may be noted to be better in
mesopic conditions. Pupil reactions are sluggish or may show
pupillary constriction in the dark, the so-called paradoxical
response. Hyperopic refractive errors are common and fundus
examination is normal. The nystagmus, although marked in
infancy, may improve with age as can the photophobia.
Peripheral visual fields are normal although a small central
scotoma can often be detected. Rod-specific ERGs are normal,
but there are no detectable cone-derived responses . Three
achromatopsia genes have been identified, CNGA3, CNGB3 and
GNAT2, which all encode components of the cone
phototransduction cascade.
The presentation and clinical findings of incomplete
achromatopsia in infancy are similar but the visual prognosis may
PROGRESSIVE RETINAL DYSTROPHIES
Most inherited retinal dystrophies occur as an isolated
abnormality but some dystrophies are associated with other
systemic abnormalities (e.g. Usher syndrome and Bardet- Biedl
syndrome) . These disorders can also be usefully divided
according to whether they predominantly affect the choroid, the
inner retina or the outer retina. Outer retinal disorders are
generally subdivided on the basis of which photoreceptors are
involved in the early stage of disease.
ROD-CONE DYSTROPHIES
The rod-cone dystrophies- often referred to as reumus
pigmentosa (RP)- are a clinically and genetically heterogeneous
group of disorders in which there is progressive loss of rod and
later of cone photoreceptor function leading to severe visual
impairment. They may be inherited as an AD, AR or XL trait.
Leber congenital amaurosis
Leber congenital amaurosis (LCA) is a rod-cone dystrophy
that presents at birth or the first few months of life with poor
vision and nystagmus; the full-field ERG is absent or
substantially abnormal. Inheritance is autosomal recessive.
PROGRESSIVE RETINAL DYSTROPHIES 54
be better. Visual acuity is often in the range 20/80- 20/ 120 and
there may be some residual colour perception. This form is also
inherited as an autosomal recessive trait and mutations in
CNGA3 have been identified.
Blue cone monochromatism (S-cone monochromatism)
Blue cone monochromatism (BCM) is an X-linked recessive
disorder affecting less than 1 in 100 000 individuals; affected
males have normal rod and blue (S) cone function but lack red
(L) and green (M) cone function. The clinical features are similar
to those of complete achromatopsia but are less severe. Affected
infants are photophobic and develop fine rapid nystagmus in
early infancy. They are usually myopic. Achromatopsia and BCM
may be differentiated by the mode of inheritance and by findings
on psychophysical and electrophysiological testing. In contrast to
achromatopsia there is some preservation of the single flash
photopic ERG in BCM and normal S-cone function can be
demonstrated by specialized spectral ERG techniques. On colour
vision testing good residual tritan discrimination is consistent
with BCM. The underlying molecular genetic basis of BCM
involves inactivation of the L- and M-opsin genes, located at
Xq28.
Affected infants have roving eye movements' or nystagmus, and
poor pupillary responses to light. Eye-poking, the 'oculodigital'
sign, is common. Fundus examination is usually normal but
disc pallor, vessel attenuation and peripheral pigmentary
retinopathy may occasionally be seen. Affected infants often
have high hyperopia.
Molecular genetic testing may be helpful in making a more
specific diagnosis. To date six genes have been identified and
account for approximately half of all patients with LCA. These
genes are expressed preferentially in the retina or the RPE and
their putative functions are diverse, including retinal
photoreceptor development (CRX), photoreceptor cell structure
(CRBJ), phototransduction (GUCY2D), protein trafficking
(AIPLJ, RPGRIPJ) and vitamin A metabolism (RPE65).
Establishing a molecular diagnosis of LCA may facilitate advice
about prognosis and allows improved genetic counselling, the
potential for prenatal diagnosis and, in the future, the selection of
patients for gene-specific therapies. This is of special interest as
gene replacement therapy with subretinal injection of
recombinant adeno-associated virus encoding an RPE65
transgene has been assessed in a dog model with promising
results. Marked improvements in visual behaviour and ERGs
occurred as early as 4 weeks after surgery in affected animals
with a gradual progressive improvement in ERG responses over
time. Trials of gene therapy in patients with LCA due to
mutations in RPE65 are likely in the near future.
RETINAL DEGENERATIONS AND DYSTROPHIES
'
int ra reti na l
pigmen tation w idespread RPE atrophy
Retinitis pigmentosa
Retinitis pigmentosa (RP) is a term used for a genetically diverse
group of disorders characterized by night-blindness and visual
field loss. ERGs are either undetectable or show the rod system
to be more severely affected than the cones with dysfunction at
the level of the photoreceptor. The age of onset is very variable.
Inheritance can be AR, AD or XL. XL and AR RP tend to have
an earlier onset and to be more severe than AD disease. The
disease may be confined to the eye or the retinal dystrophy may
be part of a systemic disorder. In most cases visual acuity is
normal at presentation, although central visual loss may occur
later as a result of posterior subcapsular cataract, macular
oedema or macular involvement. Early visual field changes are
seen as small scotomata in the mid-peripheral retina and are
more common in the upper visual field. These field defects
gradually coalesce to give the classical peripheral ring scotoma
and visual field constriction in advanced disease.
Genetics of RP
RP may be inherited as an AD, AR or XL recessive disorder, but
approximately 50 per cent of patients have no family history of
RP or evidence of parental consanguinity. It is unlikely that all
such patients have AR disease. Some males may have XL disease
transmitted via asymptomatic female carriers; other cases may
represent new AD mutations or AD disease in a family with
reduced penetrance. A significant number of patients with
sporadic RP have mild disease, and a proportion of these
probably have new AD mutations. It is also important to
remember that RP-like changes can be mimicked by posterior
segment inflammatory disease, trauma, infection and drugs.
Such patients with acquired disease may have uniocular signs
Fig. 16.58 Although the majority of patients have normal fundi
in infancy most develop signs of a pigmentary retinopathy in later
childhood with optic disc pallor and retinal arteriolar narrowing.
and frequently have better visual function and retinal
electrophysiology than is found with inherited disease.
Prior to counselling it is important to examine other family
members, especially the mothers of severely affected males who
may show fundus or electrophysiological abnormalities
suggestive of an XL heterozygote. To date, 39 loci have been
implicated in nonsyndromic RP for which 30 genes are known.
These encode a wide range of proteins including components of
the phototransduction cascade, proteins involved in vitamin A
metabolism and cell- cell interaction, photoreceptor structural
proteins and transcription factors, intracellular transport
proteins and splicing factors.
Mutations in 14 genes have now been identified for AD RP
with mutations in the rhodopsin gene being the commonest.
Clinically rhodopsin gene mutations account for about 25 per
cent of patients with AD RP and more than 60 different
mutations have been identified; there is considerable variation in
the ocular phenotype seen with the different mutations.
Mutations in 14 genes have been identified to date in AR RP
encoding many components of the rod phototransduction
cascade including rhodopsin, subunits of rod cGMP-
phosphodiesterase, subunits of rod cGMP-gated cation channels
and arrestin. In addition, mutations in four genes coding for
components of the visual cycle involved in recycling vitamin A
have been identified in AR RP. Mutations in two genes have been
identified in XL RP, RPGR and RP2. Most families with XL RP
have mutations in RPGR. It has been suggested that the protein
RPGR may act as a regulator of a specific type of membrane
transport or trafficking that is particularly active in the retina or
RPE.
 PROGRESSIVE RETINAL DYS

Fig. 16.59 The appearance of the fundus in the early stages of RP is variable but may include mild pigment epithelial atrophy in the
mid-periphery often with small white dots at the level of the RPE. Later typical bone spicule pigment deposition is seen in the equatorial
retina with arteriolar narrowing and optic disc pallor.

whitish RPE lesions attenuated arteries

Fig. 16.60 Retinitis punctata albescens, a variant of RP. Fundus

photograph showing multiple white deposits scattered throughout
the retina with macular atrophy.

gross arterial attenuati on

-!NI-'FlF'---....._,:1':1:!-L.Iil~--"--'+=-->n pale disc

Fig. 16.61 The classical fundus appearance of optic disc pallor, retinal arteriolar attenuation and peripheral retinal pigment epithelial
atrophy with 'bone corpuscle' pigmentation is seen in advanced disease . The typical intraretinal bone corpuscular pigmentation is produced
by RPE migration into the inner retina following photoreceptor loss. Other changes include vitreous cells, posterior subcapsular cataract,
optic disc drusen and macular oedema. Occasionally, retinovascular changes similar to those in Coats' disease are seen. In sector RP, the
disease may remain confined to the lower retina and this is reflected in upper field loss. This form of the disease is usually inherited as an
'AD trait and has an excellent long-term visual prognosis.
RETINAL DEGENERATIONS AND DYSTROPHIES
X-linked RP
XL RP is a severe form of RP with early onset of night-blindness
and progression to legal blindness by the third to fourth decade.
Most affected males show symptomatic night-blindness before
the age of 10 years, are often myopic, and show fundus
abnormalities and ERG changes in early childhood. Female
carriers of XL RP can be identified with certainty if they have
affected sons or fathers and are therefore obligate gene carriers
or may be shown by molecular genetic testing to carry the
Syndromic RP
RP is associated with systemic disease in a group of rare
syndromes in which renal, neurological or hearing problems are
often other features. Some of these, such as Refsum disease
(comprising RP, peripheral neuropathy, deafness,
cardiomyopathy and ichthyosis from deposition of phytanic acid)
and abetalipoproteinaemia (RP, acanthocytosis of red blood
cells, fat malabsorption, spinocerebellar ataxia and an absence of
~ (low density) lipoproteins in plasma) are important as the
biochemical defect is known and treatment can modify the
natural history. Another well known disorder is Usher syndrome
(RP and congenital sensorineural deafness). In type 1 Usher
syndrome there is profound deafness with no intelligible speech,
absent or very abnormal vestibular responses to rotation and
calories with variable ataxia. The ERG is usually absent at the
time of diagnosis. In type 2 Usher syndrome the hearing loss is
more variable and may be quite mild in some patients. The
hearing loss is most apparent at high frequencies; patients
causative mutation. m other female family members carrier
detection depends upon recognition of the abnormal fundus
appearance seen in the heterozygote or on the results of
electrophysiological testing. The retinal dysfunction in some XL
carriers appears to be progressive with symptoms of night-
blindness, detectable field loss and more extensive retinal
pigmentation.
Fig. 16.62 Fundus abnormalities are common in XL
heterozygotes. A prominent tapetal reflex may be seen at the
posterior pole or mild pigment epithelial thinning and
pigmentation may be present in the equatorial retina. The ERG is
usually abnormal in heterozygotes with delay in the 30-Hz flicker
response probably being the most frequently found abnormality,
although reduced rod amplitude may also occur.
develop speech and vestibular responses are normal. The retinal
dystrophy is of later onset and is less severe and a small ERG can
usually be recorded. A third form of Usher syndrome (type 3)
has been described that is similar to type 2 but characterized by
progressive sensorineural hearing loss. To date, 12 loci and four
genes have been identified in Usher syndrome with more
remaining to be discovered.
The mitochondrial cytopathies are an uncommon group of
multisystem disorders in which there is biochemical,
histopathological or genetic evidence of mitochondrial
dysfunction. Clinical abnormalities often begin in childhood and
may include lactic acidosis, anaemia, myopathy, neurological
abnormalities, endocrine disturbance, renal disease,
neurosensory hearing loss and an RP-like dystrophy. A number
of syndromes have been recognized including Kearns-Sayre
syndrome or chronic progressive external ophthalmoplegia (see
Ch. 2).

CONE AND CONE-ROD DYSTROPHIES
The inherited cone and cone- rod dystrophies are a
heterogeneous group of disorders characterized by variable
photophobia, reduced central vision, abnormal colour vision and
abnormal cone ERGs. AR, AD and XL recessive inheritance
have all been reported. When an inheritance pattern can be
established reliably, it is most commonly AD. The functional
deficit is confined to the photopic system in some forms of cone
dystrophy but in the majority there is later evidence of rod
dysfunction (cone-rod dystrophy; 'CORD'). The age of onset of
visual loss and the rate of progression show wide variability in
different families but visual acuity usually deteriorates over time
to 20/200 or counting fingers. In pure cone dystrophies or in the
early stages of CORD, ERG shows abnormal cone responses
with normal rod responses. With later disease generalized
atrophic macular changes
PROGRESSIVE RETINAL DYSTROPHIES
Fig. 16.63 The Bardet- Biedl syndrome (BBS) is an
autosomal recessive disorder characterized by obesity,
intellectual impairment, polydactyly, hypogonadism and
a progressive RP-like dystrophy. Renal failure, due to
ureteric reflux, and hypertension are common and are
the main causes of death. Early macular involvement is
common; a 'bull's eye' maculopathy may be seen. To
date, seven loci and five genes have been identified. The
Laurence-Moon syndrome is a closely related rare
autosomal recessive disorder in which there is no obesity
or polydactyly but affected patients have a short stature,
hypogonadism, intellectual impairment, ataxia, spinal
paraparesis and RP-like dystrophy.
abnormalities of rod and cone responses are seen with the cone
ERG being more abnormal than the rod ERG. Obligate carriers
of XL cone dystrophy may show evidence of cone dysfunction on
electrophysiological testing.
Several loci and causative genes have been identified in the
progressive cone and cone-rod dystrophies. Currently six genes
encoding various proteins, including a transcription factor,
phototransduction proteins and a synaptic protein, have been
associated with AD disease (CRX, GUCY2D, GUCAJA, RIMJ,
peripherin!RDS and AIPLJ) with more yet to be discovered.
Currently, mutations in ABCA4 have been shown to be the
commonest cause of AR CORD and mutations in RPGR have
been associated with XL CORD.
Fig. 16.64 In cone dystrophies fundus examination may show a
typical 'bull's eye' maculopathy with annular RPE atrophy and
central sparing.
;52 RETINAL DEGENERATIONS AND DYSTROPHIES

minimal macu lar changes

Fig. 16.65 In some cases there may only be minor macular RPE atrophy. The optic discs show a variable degree oftemporal pallor and
these patients can be misdiagnosed as having optic nerve disease. In this patient autofluorescence imaging shows RPE changes more
clearly. The retinal periphery is usually normal in pure cone dystrophies although rarely white flecks similar to those seen in fundus
flavimaculatus may be seen.

atrophic changes advan ced ma cular at rophy

Fig. 16.66 In patients with CORD fundus examination shows macular atrophy or a hull's eye maculopathy in the early stages (left,
middle). Peripheral RPE atrophy, retinal pigmentation, arteriolar attenuation and optic disc pallor are often seen in the late stages of the
disease process and can resemble advanced RP (right).

INHERITED CHORIORETINAL DYSTROPHIE
CHOROI DE RAE M lA
Choroideraemia is an XL recessive disorder characterized by
progressive atrophy of the RPE and choriocapillaris with
subsequent loss of the overlying photoreceptors. Affected males
usually present in early childhood with night-blindness and
progressive field loss, but central vision is usually preserved until
late in the disease. In affected males the earliest fundus signs are
fine pigment epithelial atrophy and pigmentation in the
equatorial retina; at this stage the clinical appearance may be
INHERITED CHORIORETINAL DYSTROPHIES
confused with RP. Later there is marked atrophy of the RPE and
choriocapillaris. The choroideraemia gene (CHM) has been
mapped to Xq21 with many different mutations in CHM having
been identified. The product of this gene, Rab escort protein
(REP- 1), is involved in the posttranslational lipid modification
and subsequent membrane targeting of Rab proteins, small
GTPases that play a key role in intracellular trafficking.
Fig. 16.67 Focal areas of atrophy of the RPE and choriocapillaris
develop as the disease progresses. These areas coalesce to a
widespread atrophic appearance throughout the equatorial retina.
This later spreads to involve the peripheral and more posterior
retina; the macula is spared until late in the disease. The ERG is
markedly abnormal at an early stage and is usually undetectable in
adult life.
RETINAL DEGENERATIONS AND DYSTROPHIES

granu lar changes

and hyperplasia

Fig. 16.68 Female carriers, although usually asymptomatic, show

atypical fundus appearances with widespread patchy RPE atrophy and
granular pigment deposition in the mid-peripheral retina.

GYRATE ATROPHY

Gyrate atrophy of the choroid and retina is a rare autosomal
recessive disorder characterized by progressive chorioretinal
atrophy, hyperornithinaemia and a deficiency of the pyridoxal
phosphate-dependent mitochondrial enzyme ornithine
aminotransferase (OAT). The level of OAT activity in obligate
carriers of the gene has been shown to be about 50 per cent of
normal. Children may present with night-blindness, progressive
myopia or field loss, although the diagnosis of gyrate atrophy may
be rriade in early infancy when a raised level of plasma ornithine
is found in a child with a family history. Most patients maintain
a reasonable level of visual acuity until their forties or fifties,
although with a constricted field that corresponds to the degree
of choroidal and RPE atrophy. There are small mid-peripheral
scotomata in the early stages; progression of disease leads to
marked peripheral constriction. The EOG is abnormal in most
patients and ERG changes reflect the severity of disease; early in
the disease both rod and cone amplitudes are reduced, but later
the ERG is usually undetectable. Nonocular features reported
include structural abnormalities of the hair, EEG abnormalities
and mild intellectual impairment, peripheral neuropathy and
mitochondrial abnormalities in a variety of tissues .
The human ornithine- ~-aminotransferase gene has been
cloned. A large number of different mutations of the OAT gene
have been identified in patients with gyrate atrophy including
some in which the OAT is responsive to pyridoxine. Three
different approaches to treatment have been used. A minority of
patients are responsive to pyridoxine (B 6) supplements. In
nonresponders, plasma ornithine levels may be reduced by
adhering to an arginine-restricted diet and proline
supplementation has been reported to slow the progress of
retinal degeneration in some patients.

Fig. 16.69 The earliest fundus changes are seen as small discrete
areas of choroidal and RPE atrophy in the mid and far peripheral
fundus. The atrophic areas subsequently coalesce and enlarge towards
the posterior pole, with a characteristic scalloped appearance at the
leading edge.
By courtesy of Professor Alan Bird.
 NEURODEGENERATIVE DISORDERS

NEURODEGENERATIVE DISORDERS

In addition to cone and cone-rod dystrophies, hull's eye disorders, especially Batten disease, Hallervorden-Spatz disease
maculopathy can also be seen in certain neurodegenerative and olivopontocerebellar atrophy.

BATTEN DISEASE

Batten disease (neuronal ceroid lipofuscinosis) is an autosomal
recessive disorder that occurs in infantile, late infantile and
juvenile forms. In the infantile and late infantile forms,
neurological deterioration and seizures precede the visual
deterioration, which is due to a progressive retinal dystrophy. The
ERG is extinguished at an early stage and there is marked optic
atrophy, arteriolar attenuation and a mild pigmentary
retinopathy. Juvenile Batten disease may present first to the
ophthalmologist as the visual deterioration may precede the
neurological signs. Visual loss usually starts between 5 and 8
years of age and is later followed by intellectual regression,
seizures and neurological deterioration. Death usually occurs by
the late teens. The causative gene (CLN3) has been identified.
Most affected individuals are homozygous for a 1.02-kilobase
deletion in CLN3 with the remainder having a combination of
the deletion and a second mutation. Molecular genetic diagnosis
is routinely available.

bull's eye maculopathy

Fig. 16.70 Fundoscopy usually initially shows macular atrophy with later arteriolar attenuation and peripheral retinal atrophy and
pigmentation. The ERG is substantially abnormal at an early stage. This diagnosis should be excluded in children aged between 5 and 8
years who present with visual loss and show evidence of macular atrophy and an abnormal full-field ERG by looking for the presence of
vacuolated lymphocytes in the peripheral blood. The diagnosis can be confirmed by molecular genetic testing.
56 RETINAL DEGENERATIONS AND DYSTROPHIES

TAY-SACHS DISEASE

This is a neuronal storage disorder. It is a rare, recessively disease is caused by mutations in the gene HEXA which is
inherited, neurolipidosis usually seen in Jewish infants in the first located on chromosome 15 and codes for the a-subunit of the
few months of life. Patients present with progressive neurological enzyme ~-hexosaminidase A; deficiency of this enzyme leads to
deterioration and die in the first 2- 3 years of life. Tay-Sachs excessive accumulation of ganglioside GM 2 in neurones.

cherry red white neurolipid

(neurone-free) r+--,__~ -"---'c:::...c""<---71-i stored in retinal
macula ganglion ce lls

Fig. 16.71 The abnormal material is deposited in the retinal neurones and
is seen as a whitish ring around the macula where the retinal ganglion cells
are thickest, contrasting to the redness of the relatively neurone-free macula.
By courtesy of Mr M D Sanders.

DRUGS CAUSING RETINAL TOXICITY

ANTIMALARIALS

Chloroquine and hydroxychloroquine are used in malarial
prophylaxis and treatment and as disease-modifying drugs in
connective tissue disorders such as systemic lupus erythematosus
(SLE). Retinal toxicity can occur with both drugs but
hydroxychloroquine is much less toxic and for this reason has
now replaced chloroquine in rheumatic therapy. Although the
drugs bind to melanin, their action appears to be related to their
effect on protein synthesis. Toxicity is related to daily dosage in
milligrams per kilogram and to duration of treatment. Patients
can take chloroquine for many years for malaria prophylaxis
without retinal toxicity provided the dosage regimen is not
exceeded. Patients with SLE can take hydroxychlorqine in
dosages of 6.5-7 mg/day (200-400 mg/day) for up to 10 years
without problem provided they have normal renal and liver
function. The first signs of toxicity are perifoveal granularity at
the level of the RPE and loss of the foveal reflex; continued use
may lead to a buB's eye maculopathy and eventually to a retinitis
pigmentosa-like appearance. Initial symptoms include decreased
visual acuity and paracentral scotomata. Once toxicity is
established, progressive retinal damage may continue despite
ceasing therapy. Corneal epithelial whorls are seen with
chloroquine but are of no visual significance (see Ch. 6).
 DRUGS CAUSING RETINAL TOXICITY 55

bull's eye maculopathy

concentric RPE
hyperplasia and atrophy

Fig. 16.72 This girl was treated for several years with
chloroquine for rheumatoid arthritis without adequate supervision.
Examination shows bilateral 'bull's eye' maculopathy. Visual
acuities were reduced to CF in both eyes.
THIORIDAZINE (MELLERIL)

RPE atrophy

Fig. 16.73 Phenothiazines bind to melanin and concentrate in the pigment of the uveal tract and RPE. Thioridazine (Melleril) is used as
a psychotrophic drug in schizophrenia. It will produce a pigmentary retinopathy in dosages in excess of 600 mg/day for over 8 weeks'
duration. Early toxicity is associated with fine granular RPE changes that become more pronounced with progression. Later,
hyperpigmentary changes resembling a salt-and-pepper retinopathy may develop as may chorioretinal atrophy. Some recovery follows drug
withdrawal although in some cases retinal changes will progress.

TAMOXIFEN

Fig. 16.74 Tamoxifen is an oestrogen receptor antagonist widely

used in the treatment of breast carcinoma. Retinopathy is very rare
at normal dosages but deposition of a metabolite in the inner
retina is occasionally seen in patients who have taken high dosages.
Cystoid macular oedema is the main cause of visual loss.
 DRUGS CAUSING RETINAL TOXICITY 559

QUININE

Fig. 16.75 Quinine is toxic to the neuroretina. With acute poisoning it produces a similar retinal appearance to central retina artery
occlusion, with cloudy intracellular oedema of the neuronal layer and a cherry-red spot. This is due to neuronal toxicity and swelling rather
than vascular infarction. Acute poisoning can be treated by extracorporal haemoperfusion to remove the drug from the blood. The changes
resolve over some weeks, leaving a pale disc and marked arterial attenuation. This patient took quinine as an attempted suicide. He had a
final acuity of 20/20 with grossly constricted visual fields and night-blindn ess.
The Optic Disc
Gordon Plant, David Spalton

The Normal Optic Disc

Congenital Abnormalities of Optic Disc Size and Shape
Papilloedema
Papillitis
lschaemic Optic Neuropathy
Inherited Optic Neuropathy
Optic Disc Infiltrations and Tumours
 THE NORMAL OPTIC DISC
About 25 per cent of the sensory input to the brain is visual. The
normal optic disc is oval and about 1. 5 mm in vertical diameter.
It is located in the nasal hemi-retina and the corresponding blind
spot in the visual field lies between 10 and 15° from fixation in
the temporal hemi-field, usually slightly below the horizontal
meridian. Each optic nerve contains about 1.2 million afferent
nerve fibres which are the axons of the retinal ganglion cells that
synapse at the lateral geniculate body. In addition there are
probably efferent fibres; their function is uncertain and they have
been demonstrated conclusively only in nonprimates although
they are likely to be present in humans as well.
The scleral opening is rigid and nonexpansible. Behind the
cribriform plate the axons acquire a myelin sheath and the optic
nerve enlarges to a diameter of 3-4 mm. The nerve fibres are
arranged roughly topographically in both the retinal nerve fibre
layer and the optic nerve (see Ch. 19) . The optic nerve sheath is
a continuation of the meninges and the axons in the nerve are
divided into approximately 1000 bundles by fibrous septa
(derived from the pia mater) which also carry centripetal blood
vessels. The subarachnoid space communicates intracranially so
that the nerves are surrounded by the cerebrospinal fluid (CSF)
which transmits the intracranial pressure.
ANATOMY
The optic nerve is the site of much visually threatening pathology
and it is important to understand its neuroanatomy. Based on
post-mortem studies, the number of axons in the normal human
nerve varies considerably from about 800 000 to 1.5 million with
a mean of 1.2 million. Axon diameters vary from 0.4 to 3 J.Lm
(mean 1.4 J.Lm); 90 per cent of fibres are less than 2 J.Lm in
diameter. The optic nerve has a density of about 630 000
axons/mm 2 • The axons provide about 80 per cent of the disc
substance; the rest is blood vessels (5 per cent) and glial tissue.
Choroidal artery from para -optic
posterior cil iary arteries and circle ---!~,-----
Lam ina cribrosa - - - - - - " < \ - - - - - ,'-</
Para -optic posterior ciliary - - ----,<.•/
artery trunk
o-J-lrt-----'--'------'-----tt-+--+-- - - retrolaminar optic nerve and
Fig. 17.1 Schematic diagram illustrating the arterial supply of the optic disc and distal optic nerve.
By courtesy of Miss Jane Olver.
Axons appear to be lost with age at an estimated rate of up to
5000 per year implying that the optic nerve could lose up to 30
per cent of its axons over a lifetime. Larger optic discs contain
more axons than smaller discs, in addition, the larger the disc, the
larger the area of the neuroretinal rim. Larger discs also have
larger cups than smaller discs; some discs may be so small as to
have no cup at all. Disc area varies widely between individuals,
with the largest recorded discs being six to seven times bigger
than the smallest. The area of the cup : disc ratio is commonly
used as a clinical measure of axonal quantity.
BLOOD SUPPLY
The blood supply of the optic disc is derived from the posterior
ciliary arteries; the central retinal artery which pierces the disc
does not contribute at all to the substance of the disc, supplying
only a layer of superficial capillaries to the disc surface. Two
branches of the posterior ciliary arteries, derived from the
ophthalmic artery, pass forwards in the orbit medially and
laterally and divide near the posterior aspect of the globe into two
major trunks that subdivide again. One group supplies the
choroid; the other trunk unites with its opposite number to form
the circle of Zinn, a consistent feature in human eyes. Branches
from this pass radially into the optic nerve head to supply the
retrobulbar optic nerve and the cribriform plate as well as the
prelaminar area by recurving branches. There are a few small
direct branches that enter the prelaminar region radially from the
choroid but these appear to be a relatively minor contribution to
its overall blood supply. The orbital part of the optic nerve
receives its blood supply from the ophthalmic artery by
centripetal branches entering from the pia. The venous drainage
of the disc is through the central retinal vein, the majority of
capillaries in the disc are on the venous side of the circulation.
5~~~~~~~~~===
~ -:::::::===~~--
Branch retinal
Prelamin artery
ar optic nerve
Cilioretinal artery
Reti na
~=.--- Choroid
~--7/~~ Sclera
-===-=k-~d+------- Supply to cribriform plate from
circle and choroidal arteries
~----'1\-\---\--'\-\-\---- Retrolaminal optic disc
--\-'1+-- - Dura
o--\--4\l - - - CSF
-:- - - - - ' - - - 11
+-+--+- - Pia
Centra l retina l artery suppl ies
superficial optic disc only
 THE NORMAL OPTIC DISC 5

Central
UN- , - -- -- - ----'iH-+- - - retinal
vein

Fig. 17.2 Schematic diagram of the venous drainage of the

retina, optic disc and distal optic nerve .
By courtesy of Miss J Olver.

short posterior
ciliary trunks t-'-7'-T"'T---tr::...._c:t:::~'"""<:'"'f...=2\':'-1 recu rrent branch
to optic nerve

- branch to retrobulbar
choroida l branches
from circle

Fig. 17.3 Digest preparations of a human optic disc. (Left) Posterior view showing the circle of Zinn which sends branches to the
peripapillary· choroid, the retrobulbar nerve and recurrent branches to the prelaminar region. (Right) A lateral view shows the circle of Zinn
providing branches to the choroid and retrobulbar nerve.
Reproduced by permission of ED of IOVS.
 ------·-·-------------------
564 THE OPTIC DISC

retinal nerv
fibre layer

branches of short
posterior ciliary vessels

Fig. 17.4 Low-power micrograph showing an anteroposterior section of the distal part of the optic nerve, disc and retina. There is a
considerable increase in the transverse diameter of the optic nerve after it passes through the sceral canal due to myelination. This is mostly
completed by about the time of birth, although there is possibly some increase in myelination during the first two decades of life.

optic nerve sheath

Fig. 17.5 Transverse section of the optic nerve showing the meninges and subarachnoid space and the division of nerve fibres into
bundles by fibrous septae derived from the pia mater which carry blood vessels into the nerve.

CONGENITAL ABNORMALITIES OF OPTIC DISC SIZE AND SHAPE

Normal optic discs can vary in size, shape and contour and an
accurate appreciation of this is extremely important in clinical
diagnosis. Anomalies of the disc can reflect defects in closure of
the fetal fissure, degeneration of the hyaloid vascular system, the
size of the globe (usually indicated by the refractive state but
easily measured by A scan), developmental anomalies of the
anterior visual pathways and the number of axons in the optic
nerve.
Anomalous discs can appear swollen because of distortion
and crowding of the normal nerve fibre pattern but careful
scrutiny of the disc with white and 'red-free' light usually reveals
whether a disc is truly pathologically swollen. When doubt
remains, careful observation together with serial photography
over time resolves the question. Congenitally anomalous discs
can be associated with loss of either visual acuity or field which
vanes from normality to gross deficit, the deficit is, however,
static.
 CONGENITAL ABNORMALITIES OF OPTIC DISC SIZE AND SHAPE 56

GLIAL REMNANTS

hyaloid artery
~-'"~··~·•""----1 remnant attached
to posterior
lens surface

Fig. 17.6 Glial remnants are derived from either hyaloid artery remnants or vitreous condensations and lie in front of the blood vessels
(left). Depending on their form and distribution they can simulate swelling or tumours of the disc. Occasionally, fibrous remnants of the
hyaloid artery can be seen in the vitreous, sometimes attached to the posterior pole of the lens (right). Remnants of the embryological
tunica vasculosa lentis are sometimes seen more peripherally on the lens as a Mittendorf dot (see Ch. 12).

COLOBOMAS OF THE DISC

A coloboma is a congenital defect resulting from a malclosure of
the fetal cleft. Colobomas vary in size and shape; the disc is
usually larger than normal although it may contain fewer nerve
fibres. Colobomas usually occur inferiorly with varying
involvement of the retina and uveal tract (see Ch. 9). Colobomas
are occasionally inherited in an autosomal dominant fashion and
may also be a feature of a number of genetic and
maldevelopmental syndromes such as the CHARGE syndrome
(coloboma, heart defects, anal atresia, retardation of growth,
genital and ear defects) which is caused by dysgenesis at 5- 6
weeks' gestation.

Fig. 17.7 The fetal fissure of the optic cup lies inferiorly and
normally closes (starting at the middle and spreading anteriorly
and posteriorly) at about 5-7 weeks of gestation. Defects in this
process produce a coloboma. These can occur in many shapes and
sizes, and typically involve the inferior temporal part of the disc
and sometimes the retina and choroid.

Fig. 17.8 A small coloboma of the disc associated with sectorial

hypoplasia of the inferior retinal pigment epithelium in a
pigmented eye. The disc appears slightly smaller vertically and is
wider horizontally than normal. Choroidal vessels can be seen
more easily through the thinned pigment epithelium inferiorly.
 Fig. 17.9 A large coloboma of the disc. There m ay also be
associated colobomas of the retina and choroid, lens or iris (see
Ch. 9) . A field defect is common and acuity m ay be poor if
macular fibres are affected .

'spoke-like '
rad iat ion of ~'=<__.~
retina l vessels ~~~"'""'-"--'-----1

peripapillary
pigmentation
and atrophy

Fig. 17.10 A variant of coloboma is the morning glory disc. This rare congenital deformity of the disc is characterized by a mass of
central glial tissue with radiating blood vessels, peripapillary atrophy and pigmentation. It is sometimes called a central coloboma of the
disc. In these eyes the optic disc lies posterior to the globe 'within' the optic nerve, creating a funnel-shaped defect plugged by a central
glial mass.
 CONGENITAL ABNORMALITIES OF OPTIC DISC SIZE AND SHAPE

basal
encephalocele

Fig. 17.11 In these patients the vision in the affected eye is poor and there may be associated midline intracranial anomalies such as a
basal encephalocele. This is especially true if there are signs of mal closure of the fetal facial clefts, such as palatal deformity or telecanthus.

atrophy
.,.,.~____, larger disc

=== colobomatous
defect

Fig. 17.12 Colobomas can be associated with serous macular detachments. This patient has an anomalous disc with a colobomatous area
inferiorly associated with longstanding serous detachment of the macula with subsequent retinal pigment epithelial changes.
 large
c._o>.""-~---1 physiological
cu p

Fig. 17.13 This patient has larger than normal discs. The right
disc has colobomatous features. The neuroretinal rims are irregular
and the physiological cups are large, simulating glaucoma.

OPTIC DISC PITS

Fig. 17.14 (Left) A pit ofthe optic disc has a greyish appearance and lies in the temporal or inferior border of the disc (which is of
normal or slightly larger diameter), penetrating deeply into its substance. Pits centred on the papillomacular bundle are frequently
associated with a centrocaecal field defect; inferior pits produce superior arcuate field defects. Some patients, as in this example, have
serous detachment of the macula and usually present with visual loss in early adulthood. (Right) A late-stage fluorescein angiogram shows
hypofluorescence of the pit. The aetiology of macular detachment is thought to be transmission of fluid from the vitreous through the pit
producing a retinal schisis.

OPTIC DISC HYPOPLASIA
Hypoplasia of the disc is an important physical sign as small
optic discs transmit fewer axons than normal and a hypoplastic
optic disc may be associated with poor acuity, field defect,
strabismus or failure to improve with amblyopia treatment.
Conversely, optic disc swelling can be simulated by a large
number of axons passing through a small optic disc.
CONGENITAL ABNORMALITIES OF OPTIC DISC SIZE AND SHAPE 5
Characteristically the optic disc looks 'small', especially when
compared to a normal fellow eye and there may be a disparity
between the retinal and scleral aperture. The visual deficit can
vary from normal to severely defective. Severe forms of
hypoplasia can also be associated with intracranial
developmental defects of the anterior visual pathway.
crowded
nerve p-......,j;iiO
disparity between
fibres
E'-----++P~7'fl=~--==,.__~'-l retinal and sclera l
opening
Fig. 17.15 This patient was referred with suspected
papilloedema. Both optic discs are small, the left more so and
slightly tilted, and the disparity between the retinal and scleral
openings can be seen in both eyes. The right disc is small and full.
There is crowding of the nerve fibres on the nasal side of each
disc, simulating swelling.
myopic RPE
normal RPE changes
small tilted
optic disc
exposed sclera
Fig. 17.16 Tilted discs are commonly seen in highly myopic
eyes. This patient has a rather small disc in the right eye but the
left eye is myopic with a tilted hypoplastic disc.
 Fig. 17.17 The same patient had an associated cleft palate defec1
suggesting that the optic disc anomaly is part of a maldevelopment
defect.

Left eye Right eye

Fig. 17.18 These are the visual fields of the

same patient. Fewer axons than normal enter
the disc in the defective area and there is
corresponding fundu s ectasia (as shown by the
thin retinal pigment epithelium in F ig. 17 .16);
together these features result in a visual field
defect. As the defect is usually inferonasal this
produces a superotemporal field defect
simulating chiasma! compression. Such defects,
however, cross the vertical meridian, a feature
n ever seen with neurological causes of field
loss. Furthermore, the refractive component
can be corrected by additional myopic
correction and these characteristics allow the
correct diagnosis to be made.

nerve fibres

Fig. 17.19 Optic nerve hypoplasia is seen in its m ost severe form as part of the rare syndrom e of septo-optic dysplasia. These children
have very poor vision and associated midline intracranial anomalies, of which an absent septum pellucidum is typical. Abnormalities of
pituitary hormonal functi on, especially growth hormone deficiency, are common. The right optic disc is grossly hypoplastic, although some
nerve fibres are present; the left contains virtually no nerve fibres at all. This child h ad short stature as a result of growth hormone
deficiency and acuity of 20/40 and PL.
By courtesy of Professor D Taylor.
 t iny opt ic nerves single ventricle

Fig. 17.20 Magnetic resonance image of

another child shows tiny optic nerves in
the orbit. The septum pellucidum is
absent, resulting in a single lateral
ventricle.
By courtesy of Dr R Hoare.

sectorial nerve fibres

Fig. 17.21 This patient presented with

congenital nystagmus. Both optic discs
show gross sectorial temporal hypoplasia.
Such patients require neuroimaging to
detect associated maldevelopment of the
anterior visual pathway.
72 THE OPTIC DISC
ANOMAliES ASSOCIATED WITH AXIAL LENGTH
The axial length of the eye will also influence the size and shape
of the optic disc. Hypermetropic eyes are smaller in size than
normal and consequently optic discs are frequently smaller, do
not have a physiological cup and have a crowded or 'full'
appearance that can suggest swelling. Retinoscopy or A scan
gives the clue to the underlying aetiology. Myopic discs tend to
Fig. 17.23 Myopic discs have associated peripapillary atrophy and a temporal crescent. Because of the larger intraocular surface area, the
retinal pigment epithelium and choroid appear to be thinned and pale and sometimes the temporal retinal vessels are stretched into a
posterior pole staphyloma (see Ch. 15).
be larger and surrounded by a white crescent of bare sclera on
the temporal side occasionally with some pigmentation along the
border. The physiological cup is normally broad and shallow and
the disc tends to be paler than in emmetropic eyes. These
changes can mask glaucomatous changes for the unwary.
crowding of
nasal nerve fibres
mi nimal cup
crowding of nasal
nerve fi bres
sm all disc
Fig. 17.22 The appearance of the optic discs in a patient with
+6D of hypermetropia in each eye and axial lengths of 21 and
20.7 mm. The discs are small and full with a crowded nerve fibre
pattern and minimal cupping.
 CONGENITAL ABNORMALITIES OF OPTIC DISC SIZE AND SHAPE

border of retinal G~~~~~~=~===:::;::;;:S:l

pigment
epithelium

exposed sc lera
crib riform plate

Fig. 17.24 · Histological examination of a myopic disc shows that

the retinal aperture of the optic disc is larger than the scleral
aperture with a deficiency of retina and choroid on the temporal
side revealing the bare sclera. There is temporal traction of the
blood vessels caused by the stretching or pulling of the retina into
the expanded posterior pole of the eye.

MYELINATED NERVE FIBRES

Optic nerve myelination is usually completed by about 9 months retinal oedema in a wide variety of patterns. The presence of
of gestation. Myelinated fibres sometimes spread on to the myelinated nerve fibres is usually inconsequential although
surface of the disc or surrounding retina in feathery white grossly affected eyes often have poor vision .
patches that can simulate disc swelling, cotton-wool spots or

Fig. 17.25 A highly magnified view of myelinated axons on the

retina.

Fig. 17.26 This patient was referred because she was thought
to have cotton-wool spots on the disc. She has small areas of
myelination of nerve fibres superiorly and inferiorly on the right
disc (left) and inferiorly on the left disc (right) simulating cotton-
wool spots.
574 THE OPTIC DISC

Fig. 17.27 These eyes from two different patients show more marked changes.

DRUSEN OF THE DISC

These opalescent excrescences are seen on the surface of the disc
or buried in its substance. Pathologically, drusen are thought to
be derived from calcified axonal debris. Typically, the retinal
vessels exit centrally and branch anomalously on the disc surface;
the disc is smaller than normal and has a swollen or full
appearance with no physiological cup. These signs can be
mistaken for papilloedema. Arcuate nerve fibre defects and
subretinal peripapillary haemorrhages are common. There are
associations between drusen of the disc and retinitis pigmentosa
and angioid streaks.

Fig. 17.28 This patient has typical

exposed drusen
anomalous branching
of central retinal artery
anomalous branching
\?===-'-""'~ of centra l retinal artery
exposed drusen. Note the discs are
relatively small, there is no cup and
the vascular pattern is anomalous
with the vessels exiting centrally. The
central retinal artery divides
immediately into five branches. The
patient had markedly constricted
fields.
 CONGENITAL ABNORMALITIES OF OPTIC DISC SIZE AND SHAPE

subretinal haemorrhage

Fig. 17.29 This patient was referred with

disc appears swollen suspected papilloedema. Note the subtle
drusen in each eye and the anatomical
anomalies are similar to those in Fig. 17.28.

calcific drusen

Fig. 17.30 Buried disc drusen can be a diagnostic

problem. Exposed drusen autofluoresce in blue light;
buried drusen can be demonstrated by B-scan
ultrasonography or axial computed tomography
through the optic nerve head when calcification is
seen in the drusen within the optic disc .
ANOMALOUS VASCULAR CHANGES

Fig. 17.31 Optic discs with

congenitally anomalous blood vessels are
often mistakenly thought to be
pathologically swollen. These discs are of
small size with no physiological cup with
vessels that exit centrally in an
anomalous pattern. On the retina there is
congenital tortuosity, largely affecting
retinal veins, with typical reverse loops
pointing backwards towards the disc, a
sign of congenital vascular tortuosity. The
reverse venous
loop retinal nerve fibres are not swollen and
do not cover the vessels; furthermore, the
superficial vascular plexus on the disc is
not dilated.

Fig. 17.32 Dual pathology can

coexist. This patient has anomalous
discs and congenital vascular tortuosity
chronic congenital vascular
papilloedema but in addition has papilloedema from
tortuosity
retinal k--=1'~.:.'~'k=~ anoma lous vascular chron ic c:.+~rF=I=....c-+--1 anomalous vascu lar
benign intracranial hypertension. Note
haemorrhage pattern papilloedema pattern the retinal and subretinal
subretinal haemorrhages and chronically swollen
haemorrhage optic discs.
 PAPILLOEDEMA

PAPILLOEDEMA

It is frequently difficult to determine the aetiology of pathological
optic disc swelling merely by disc appearance and in many cases
it is impossible. Correct diagnosis depends on eliciting an
accurate history and other physical signs. Any patient with
suspected optic disc swelling needs a careful history and
examination of visual acuity, refraction, colour vision, pupillary
responses, ocular movements and visual fields of both eyes before
a diagnosis is made.
Papilloedema implies optic disc swelling due to raised
intracranial pressure. Although neuroimaging with computed
tomography or magnetic resonance imaging helps with diagnosis,
papilloedema, especially if early, can still be missed and this may
have serious implications. The optic disc should be carefully
scrutinized stereoscopically with white and green 'red-free' light
to show vascular and nerve fibre detail more easily. Features to
look for are dilatation of the retinal nerve fibres, particularly at
the nasal disc border, dilatation of the superficial disc capillary
plexus and haemorrhages in the surrounding nerve fibre layer.
The presence of retinal folds (Paton's folds), choroidal folds,
venous dilatation and shunts, absence of venous pulsation and
the size of the optic disc itself are all important features in
distinguishing pathological swelling from pseudo-papilloedema.
Apart from transient obscurations of vision, papilloedema
does not produce visual symptoms until very late in its course.
Obscurations are episodes of unilateral or bilateral visual loss
lasting for a few seconds during which the patient notices a
greying out of vision that rapidly returns to normal. They are
sometimes related to bending, straining or a Valsalva manoeuvre
and patients may have repeated episodes during the day. Patients
with raised intracranial pressure may have diplopia from sixth
nerve palsies caused by compression of the nerve as it crosses the
apex of the petrous temporal bone. Prolonged papilloedema
leads to nerve fibre destruction and field loss but visual acuity is
not usually affected until the terminal stages. Papilloedema may
be subdivided on descriptive grounds into early, acute, chronic or
atrophic stages.
EARLY PAPILLOEDEMA
The degree of papilloedema is influenced by the severity, rate
of increase and duration of the CSF fluid pressure rise as well
as local factors in the optic nerve sheath or at the optic disc
itself.

artifactually
detached retina ~~~:==:::s,

edgeof ~6~~~~~/
Bruch's P==-=-":=""c±d+~ " choroid
membrane

lamina
crib rosa

Fig. 17.33 The earliest histological feature seen in any swollen disc is axonal dilatation following hold-up of orthograde axoplasmic
transport in the retinal neurones as they pass through the cribriform plate. Axoplasmic transport is a complex traffic of intracellular
organelles from the cell nucleus to the synapse (orthograde) or vice versa (retrograde) (see Ch. 13). Vascular engorgement and oedema add
to the swelling but the initial changes are found in the nerve fibres. The precise mechanism causing the axoplasmic delay is not well
understood but probably consists of a mixture of hypoxic, mechanical and vascular factors.
By courtesy of Professor P Luthert.
THE OPTIC DISC

Fig. 17.34 Progressive changes of papilloedema are seen in a patient with an intracranial tumour who declined treatment. (Top left)
Early nerve fibre dilatation is seen particularly superiorly, inferiorly and nasally. (Top right) This increases and venous engorgement
develops. (Bottom left and right) Temporal nerve fibre dilatation and swelling of the disc increases and haemorrhages and possibly cotton
wool spots appear.
 PAPILLOEDEMA 57

su perficial and deep leakage

into disc in later phase
of angiog ram

Fig. 17.35 Fundus photography (left) and fluorescein angiography (middle, right) can be extremely useful in establishing the diagnosis of
papilloedema and in monitoring its progress. Swollen optic discs show dilatation of the superficial capillary plexus on the disc surface
(middle) and deep leakage within the disc in the later stages of the angiogram (right). Although these changes confirm that the disc is
swollen, they do not differentiate the cause. Furthermore, caution is required as crowded anomalous discs sometimes stain with fluorescein
in the late phases of the angiogram.

Fig. 17.36 Orbital computed

tomograms of patients with raised
intracranial pressure show dilatation of
the optic nerve sheaths with CSF and
tortuous dilated 1-:;;~~~;;;::--l provide useful ancillary diagnostic
optic nerve sheaths information in difficult cases. Dilatation
of the optic nerve sheaths from CSF
must be distinguished from thickening
due to, for example, inflammation or
meningioma.
THE OPTIC DISC

ACUTE PAPILLOEDEMA

At this stage the discs are swollen and hyperaemic with haemorrhages and cotton-wool spots on the surface. Retinal axons are dilated
but there is no loss of nerve fibres.

Fig. 17.37 This patient presented with

severe headache with metastases from
carcinoma of the bronchus. The discs show
florid haemorrhages with relatively little
swelling, indicating a rapid dramatic increase
in CSF pressure.

Fig. 17.38 This patient had a posterior fossa

' swollen disc
++!"""""-"-*~=' haemorrhage
haemorrhage
tumour. These tumours can readily compress
the aqueduct in the midbrain and produce an
acute rise in CSF pressure. Both discs are
grossly swollen with dilated nerve fibres,
swollen disc
masking the blood vessels at the disc borders.
There are haemorrhages into the nerve fibre
layer around the disc and cotton-wool spots on
the disc surface. These are signs that the patient
has suffered a rapid rise in intracranial pressure.
The optic cup is still preserved.
 PAPILLOEDEMA

Left eye Right eye

Fig. 17.39 Acute papilloedema is

associated with full visual fields, normal
visual acuity and colour vision . The blind
spots are enlarged as a result of lateral
displacement and masking of photoreceptors
by swollen nerve fibres, together with
accumulated subretinal fluid and hyperopia
induced by a more rigid and dilated optic
nerve sheath pressing on the globe.

CHRONIC PAPILLOEDEMA

At this stage fewer haemorrhages and cotton-wool spots are Choroidal folds and retinochoroidal venous collateral vessels
present. With chronicity, nerve fibre loss starts to occur, the (formerly called opticociliary shunt vessels) may be present.
swelling becomes less prominent and the discs become paler.

Fig. 17.40 This patient with benign intracranial hypertension has gross disc swelling with no haemorrhages or cotton-wool spots
indicating a slow rise in CSF pressure to a severe level.
2 THE OPTIC DISC

Fig. 17.41 Papilloedema is usually

bilateral but can be very asymmetrical.
This patient has much more marked disc
oedema in the left than in the right eye,
indicating that for some reason the
increased CSF pressure has not been
transmitted to the right optic disc.
Subretinal peripapillary haemorrhage is
seen in both eyes.

Fig. 17.42 Choroidal folds are produced by the comparatively rigid and distended optic nerve sheath indenting the globe. They are due
to folding of the RPE. When associated with papilloedema they normally lie in a horizontal axis. They are much more visible in fluorosein
angiography.
 haemorrhages

Fig. 17.43 Papilloedema with a macular star. This is one of the few
occasions in which papilloedema is accompanied by decreased visual acuity.
Macular stars result from plasma lipoproteins leaking from a swollen optic
disc and are sometimes seen with either chronic papilloedema or resolving
papilloedema following treatment. They are particularly common with
ischaemic optic disc swelling, from which papilloedema should be
distinguished. The lipoprotein exudate lies within the radiating nerve fibres of
Henle surrounding the macula and is usually more marked on the nasal side.

SI NGL E FI ELD ANALYS I S

[ NAME: OOBI 20-02- 1977[
Slt.!CI....E FIELD AIIALYSlS EVE t RIGHT
I~· COB I 20-02- 1977[

lll![tJitll
fiDIIOIIUIIIMtWIIkl.lnl
IIU:H
/lUIIOIIIIttlltCUillll

f .._lol:niU~t I t
fllllllltlltmt IX

., ......., I I I I ·l·U
·I ., -~ "' ., ., ·l·l I ·J I I
·I ·I ·It·'
·•
·li·V·ll ., ., ·l -i ·lS ·Z2 ·11 I I I ·I I
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·ll ·ll·!l·ll-t -1-t·J ·!l-U ·12 ·I ·I ·l ·I ·I
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Fig. 17.44 Computerized fields (Humphrey 24- 2 protocol) from a patient with bilateral chronic papilloedema. Inferonasal field loss is
usually found as the earliest change. As papilloedema becomes chronic there is progressive nerve fibre loss which is usually seen as an
inferior arcuate defect; note also the enlarged blind spots. With progression further loss is seen in the superior and inferior arcuate regions.
Ultimately the patient is left with preservation of only the central visual field resulting in 'tunnel' vision.
 IRE OPJJC DISC

ATROPHIC PAPILLOEDEMA

With prolonged raised intracranial pressure the discs become paler with residual swelling. There is gross nerve fibre loss and poor visual
function.

gross swelling

di lated superficial
capilla ries

less disc
swelling
choroidal
folds

disc pallor disc pallor

residual disc
choroidal
swelling
folds

Fig. 17.45 This patient had raised CSF pressure from a glomus tumour. There is gross chronic oedema of both optic discs. He was
treated with bilateral optic nerve sheath fenestrations. One month later there is considerable improvement in the disc appearances. Four
months after surgery there is residual swelling with pallor more marked in the right than the left eye, signifying axonal loss. Choroidal folds
can be seen in the right eye; these frequently persist after resolution of raised CSF pressure due to retinal pigment epithelium damage.

corpora amylacea
Fig. 17.46 Sustained intracranial pressure over
a prolonged period eventually leads to pallid
swollen discs with tiny opalescent excrescences
on the disc surface, representing debris from
axonal damage and sometimes referred to as
corpora amylacea. Nerve fibre loss can be seen
ophthalmoscopically in the retina . These discs
sometimes have an appearance superficially
similar to drusen of the disc.

Fig. 17.47 With atrophic papilloedema nerve fibres are eventually

destroyed and the optic disc without viable nerve fibres does not
swell (if there are no axons left there can be no hold-up of
axoplasmic transport). This patient had longstanding benign
intracranial hypertension. The discs are pale and slightly swollen,
and there is some arterial attenuation. Retinochoroidal venous
collaterals are present (a sign that there has been chronic swelling of
the disc) shunting blood from high pressure in the central retinal
vein to lower pressure in the choroidal circulation to leave the eye by
the vortex veins. The visual fields will be grossly and irreversibly
constricted with poor visual acuity. At this stage sudden lowering of
the CSF pressure can precipitate acute visual loss.
By courtesy of Mr MD Sanders.

PAPILLITIS
Papillitis describes swelling of the optic disc caused by local
inflammation of the optic nerve head. It is accompanied by signs
of optic neuropathy: reduced visual acuity, colour desaturation,
an afferent pupillary defect and a central scotoma in the visual
field. Optic disc swelling from papillitis cannot normally be
distinguished from that due to other causes by appearance alone
although it is usually less florid with fewer haemorrhages and
cotton-wool spots.
Papillitis is usually acute and unilateral. It is seen most
commonly in young adults with demyelinating disease in
association with multiple sclerosis although there are many other
rarer causes. In the acute stage it is associated with retrobulbar
pain, with tenderness and pain on ocular movement. These
symptoms may be less dramatic than when seen with acute
Fig. 17.49 The left eye of this 25-year-old woman is normal but there is mild swelling of the right disc. In this eye the visual acuity was
reduced to counting fingers; no Ishihara plates could be recognized and there was some pain on ocular movement and tenderness on
retropulsion of the globe.
arterial less pallor and
attenuation more swollen disc
Fig. 17.48 Another patient with cryptococcal meningitis shows
terminal papilloedema. The right eye (left) had perception of light;
note the pale atrophic disc, minimal swelling and marked arterial
attenuation. In the left eye (right), the visual acuity was 20/200 and
the disc pallor is less and there is more swelling.
retrobulbar neuritis which has the same clinical features of acute
visual loss over a few days with pain on ocular movement but
without disc swelling. About 50 per cent of patients with clinical
features of demyelinating optic neuritis have some disc swelling.
Magnetic resonance imaging shows that this is more common
with anteriorly sited demyelinating lesions in the optic nerve
although disc swelling can occur with lesions in any part of the
orbital optic nerve and the former rather rigid clinical distinction
made between papillitis and retrobulbar neuritis has become less
important.
In children papillitis occasionally follows viral respiratory
infections or the exanthemata; this is usually bilateral and
simultaneous and recovers spontaneously with a benign visual
and neurological prognosis.
mild opti c
disc swefring
 PAPILLITIS

normal disc

Fig. 17.50 Fluorescein angiography shows deep staining of the disc in the late phases. Although no definite distinction can be made
between swelling due to papilloedema or papillitis, the latter is usually less marked with fewer haemorrhages and cotton-wool spots. With
papillitis there may sometimes be a low-grade vitreous cellular infiltration. Sheathing of the peripheral retinal veins, similar to that seen
with a low-grade retinal vasculitis (see Fig. 10.27 and Fig. 17 .53), is seen in about 25 per cent of patients with acute demyelinating
retrobulbar neuritis; these are known as Rucker's lines after the Mayo Clinic neurologist who first described them.

Left eye Right eye

Fig. 17.51 The left visual field is normal; the

right has a large central scotoma. This can be
easily demonstrated at the bedside by using a red
target and a confrontation visual field to show
central desaturation. The visual evoked potential
(VEP) will show a reduction in amplitude with
considerable delay of the waveform; as the vision
improves, the amplitude recovers but the delay
remains. VEPs are particularly useful for
detecting subclinical demyelination in the fellow
eye (see Ch. 1) .

Fig. 17.52 This patient presented with symptoms of left acute optic neuritis with parasthesiae in his right leg. At presentation (left two
figures) both optic discs look grossly normal although the nerve fibre outline in the left eye is slightly more blurred. Eight weeks later (right
two figures) there is definite pallor of the left optic disc.
;as THE OPTIC DISC

periphebitis

Fig. 17.53 This patient shows the typical low-grade periphlebitis seen with optic
neuritis.

white matter latera l ventricles

Fig. 17.54 Magnetic resonance imaging

shows focal white matter lesions with a
prediliction for the periventricular area in
about 50 per cent of patients presenting
with optic neuritis. Gadolinium
T2 wei ghted seam enhancement shows the lesions are of recent
onset. The presence of typical MRI lesions
correlates with a substantially increased risk
of developing MS.

Fig. 17.55 Magnetic resonance image of a

patient with optic neuritis of the left optic nerve
shows a high signal intensity in the nerve when
compared to the right nerve.
 ISCHAEMIC OPTIC NEUROPATHY

ISCHAEMIC OPTIC NEUROPATHY

NONARTERITIC ANTERIOR ISCHAEMIC OPTIC NEUROPATHY

The optic disc receives its blood supply from the short posterior
ciliary arteries and acute interference with this blood supply will
produce a unilateral infarcted disc that is pale and swollen with
surrounding nerve fibre haemorrhages. For some unknown
reason this tends to occur sectorially with the superior
hemisphere of the disc being affected most commonly. The
inferior hemisphere of the disc can be compromised by the
adjacent infarct and sometimes appears to be more hyperaemic
and more swollen. This produces asymmetrical disc swelling.
Nonarteritic anterior ischaemic optic neuropathy is more
common in hyperopic eyes with smaller, crowded optic discs (the
so-called 'disc at risk'), and in atherosclerotic or hypertensive
individuals. Other uncommon predisposing factors are acute
hypotension (e.g. following critical illness, major surgery or
excessively treated hypertension) and occasionally vasculitis, a
prothrombotic disorder or migraine. Patients typically present in
late middle age with sudden painless loss of vision in one eye and
are found to have an altitudinal field defect. If macular fibres are
damaged, acuity is lost as well. Vision sometimes deteriorates
further for a few days after onset, possibly as a result of
oedematous compression of the remaining viable nerve fibres . A
substantial number of patients, however, experience some visual
improvement over the next few weeks as the infarct subsides.
Unfortunately no effective acute treatment is available; use of
aspirin to prevent fellow eye involvement is controversial.

sectorial hypofluorescence

pa le swelling

Fig. 17.56 This patient shows the typical features of nonarteritic ischaemic optic neuropathy 3 weeks after the onset of acute visual loss
in the right eye. The disc is small, the superior pole is pale and the inferior pole shows pale swelling (left); the angiogram shows
hypofluoresence superiorly in the early stages and later leakage (right). Note the peripapillary choroid fills normally.
asymmetrical
optic atrophy
disc swelling

haemorrh age
and cotton -wool
spots

Fig. 17.57 About 30 per cent of patients will have involvement of the second
eye within 2 years . This patient has a pale left disc from previous nonarteritic
relative anterior ischaemic optic neuropathy. Early and late fluorescein of the right disc she
hypofluorescence acute changes, more marked in the inferior pole of the disc, with relative hypoflu01
superiorly.
 ISCHAEMIC OPTIC NEUROPATHY

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shows a typical lower altitudinal field defect of nonarteritic anterior
ischaemic optic neuropathy.

ISCHAEMIC OPTIC NEUROPATHY DUE TO TEMPORAL ARTERITIS

Temporal arteritis must be considered in any person over 56 temporal headaches, neckache or stiffness, jaw claudication,
years of age who presents with sudden loss of vision and the malaise or weight loss in addition to polymyalgia and morning
clinical appearances of ischaemic optic neuropathy. In making stiffness.
this diagnosis it is helpful to seek a history of characteristic

Fig. 17.59 The temporal arteries of this woman were tender, inflamed, thickened and nonpulsatile, although frequently the signs are
more subtle. The diagnosis is suggested by finding a high erythrocyte sedimentation rate (ESR) and C-reactive protein level and confirmed
by temporal artery biopsy. Prompt treatment with steroids is required as there is a grave risk of fellow eye involvement or stroke.
i92 THE OPTIC DISC

l,j~

~'
Fig. 17.60 Patients can develop scalp ischaemia from the arteritis.

Fig. 17.61 Patients typically present with a chalky white swollen disc with few
haemorrhages.

delayed choro idal fill ing

Fig. 17.62 The optic disc of this elderly woman who suddenly lost vision in the right eye is completely infarcted, pale and slightly swollen
with a small cilioretinal infarct (left), which is, of course, supplied by the posterior ciliary circulation. The fluorescein angiogram in the
early venous phase (middle) shows delayed filling of the optic disc and peripapillary circulations due to involvement of the short posterior
ciliary arteries that supply the disc and adjacent peripapillary choroid with some leakage of dye into the optic disc. Such delay in filling of
the peripapillary choroid distinguishes arteritic from nonarteritic ischaemic optic neuropathy. The left optic disc shows filling defects
indicating subclinical involvement of the posterior ciliary circulation and impending doom. Central retinal artery occlusion can occur in
temporal arteritis but is uncommon.
 ISCHAEMIC OPTIC NEUROPATHY 593

Fig. 17.63 Temporal artery biopsy following presentation is

essential to confirm the diagnosis and should be done within the
first 48 hours as steroid therapy may affect the histological
interpretation. These elderly patients may need prolonged systemic
steroid therapy to control the arteritis and commonly suffer
treatment side-effects. It is therefore essential to be sure that the
diagnosis is well substantiated. The biopsy of this patient shows
inflammatory changes throughout the entire arterial wall but these
are concentrated mainly in the media with fragmentation of the
internal elastic lamina; there are multinucleated giant cells and
gross narrowing of the lumen. Skip lesions can occur and it is
necessary to examine sections at different levels to exclude this
possibility.

Fig. 17.64 This eye shows the resolving phases of arteritic

ischaemic optic neuropathy 4 weeks after the acute incident. Note
the pale atrophic disc and mild macular star. The retinal vessels are
grossly attenuated in this eye although this is not a consistent
finding .

disc normal

loss of neuro-
retinal rim

Fig. 17.65 A unique feature of arteritic ischaemic optic neuropathy is that on resolution the disc can develop cupping that is
indistinguishable from glaucomatous cupping. This is sometimes cited as circumstantial evidence that glaucoma has an underlying vascular
aetiology.
94 THE OPTIC DISC

INHERITED OPTIC NEUROPATHY

Inherited optic neuropathies are rare. The two seen most optic neuropathy (LHON) and autosomal dominant optic
commonly in neuro-ophthalmic practice are Leber's hereditary atrophy (ADOA).

LEBER'S HEREDITARY OPTIC NEUROPATHY

LHON is an intriguing disease that is inherited through the
maternal mitochondrial DNA in the cytoplasm of the ovum.
Mature sperm contain virtually no cytoplasm and mitochondria
so affected men cannot transmit the gene and children inherit the
disease exclusively from their mother. Three mutations (11778,
3640, 14484) account for the majority of cases. These genes
encode respiratory chain enzymes for oxidative phosphorylation.
The '11778' defect is most common (found in more than 50 per
cent of cases), involving an amino acid substitution at this point
in the mitochondrial genome. Organs within the body can be
variably affected, some having cells with a normal genome, and
others having cells that are partially or completely affected; this
is known as heteroplasmy.
Men are usually affected; it is not known why LHON affects
women so rarely. The typical case is a man aged 20- 40 years with
bilateral sequential painless visual loss affecting each eye over a
few months. Many atypical cases such as unilateral disease and a
much wider age range are being reported now that the LHON
genotype can be identified. Patients usually lose central vision to
about counting fingers but a few may have excellent spontaneous
recovery of acuity many years later, particularly if they have the
11778 genotype. Cardiac conduction defects are relatively
common. Many patients have a characteristic peripapillary
micro-angiopathy which precedes the acute visual loss. This acts
as a marker for the disease but does not predict whether the
patient will develop visual problems or when. The MRI is normal
in the acute phase and the nerve does not enhance with
gadolinium, presumably because there is no inflammation as the
axons have suffered a 'metabolic' insult. Later imaging shows
high-intensity signal throughout the orbital and intracranial optic
nerve on T2-weighted images due to axonal degeneration.
No treatment is available but family members should be
advised not to smoke or drink excessively as this is thought to
predispose to the development of the optic neuropathy in those
who have the genetic abnormality. Studies are in progress to
ascertain whether antioxidants targeted at mitochondria might
be given when the first eye is affected in order to prevent second
eye involvement.

Fig. 17.66 This patient had suffered acute loss of vision in his right eye 6 weeks previously and presented with acute visual loss in the left
eye. The right disc (left) is becoming pale but the retinal axons are still dilated and the vascular tortuosity is less marked than in the left eye
(right) where telangiectatic vessels can be seen in the dilated and prominent nerve fibre layer surrounding the disc.
 INHERITED OPTIC NEUROPATHY 59

Fig. 17:67 .Fluoresce~n angiography shows the telangiectatic vessels but, in unique contrast to other types of disc swelling, these do not
leak; neither IS there evidence of any pathological leakage into the optic disc itself.

AUTOSOMAL DOMINANT OPTIC ATROPHY

ADOA is inherited as an autosomal dominant disorder caused by
mutations of a nuclear DNA gene that encodes a mitochondrial
enzyme known as OPAl. Thus there is a pathophysiological
similarity to LHON but the clinical presentation is very
dissimilar. Affected family members are rarely thought to have
anything wrong with their vision until their late teens when, for
example, they may not have good enough vision to pass a driving
test. There is then progressive bilateral and symmetrical visual
loss throughout life, culminating in visual acuity of around
20/200 by the age of 60 years. Affected presymptomatic children
in the family can often be identified clinically by optic atrophy
and impaired colour vision. Polymorphisms of the OPAl gene
have been associated with normal tension glaucoma.

Fig. 17.68 This 13-year-old girl presented with a visual

acuity of 20/60 in each eye and poor colour vision. Her
mother had never had good enough vision to meet the
legal acuity requirements to drive.
596 THE OPTIC DISC

OPTIC DISC INFILTRATIONS AND TUMOURS

The optic disc can be infiltrated by primary intraocular tumours
such as retinoblastoma or choroidal melanoma and rarely by
lymphoma, metastases or optic nerve tumours. Carcinomatous
meningitis is normally associated with either a normal disc
appearance or pallor, depending on the duration of symptoms.
Inflammatory granulomas such as sarcoid are the most common
cause of infiltration. This diagnosis is suggested by a cellular
vitreous infiltrate and periphlebitis of the retinal veins; the effect
on visual function is variable.

INFLAMMATORY INFILTRATION

mild disc swel li ng

Fig. 17.69 Sarcoid can cause disc swelling secondary to posterior uveitis as a result of optic
nerve infiltration or from raised CSF pressure. Patients may also present with primary optic
atrophy. This patient presented with mild swelling of the left optic disc with some pallor of the
right disc. She had pulmonary sarcoid.

Fig. 17.70 Magnetic resonance

imaging of the same patient shows a high
signal from the thickened left optic nerve
in the posterior orbit.
 OPTIC DISC INFILTRATIONS AND TUMOURS

arachnoid

dura

multinucleate
giant cell

Fig. 17.71 This optic nerve biopsy was taken from a 46-year-old patient with a chronic progressive unilateral optic neuropathy eventually
resulting in a blind eye. The patient then started to develop a visual field defect in the fellow eye. MRI showed bilateral optic nerve
thickening. Biopsy confirmed the suspected diagnosis of sarcoid optic neuropathy.

TUMOURS

Fig. 17.72 A melanocytoma is a densely pigmented benign tumour that is usually situated in the inferior part of the disc and is more
commonly found in dark-skinned people and pigmented eyes. The disc is usually larger than normal. The lesion may increase in size slowly
and protrude into the vitreous or spread out on to the retina, in which case differentiation from a malignant melanoma of the choroid can
be exceptionally difficult. Field defects can occur although visual acuity is not normally affected. No intratumour circulation is seen on
fluorescein angiography. (See also Ch. 9.)
598 THE OPTIC DISC

ASTROCYTIC HAMARTOMAS

These tumours arise from the retinal glial tissue and usually
occur in the posterior pole. They may be bilateral and an eye can
have multiple lesions. Although isolated ocular lesions do occur,
astrocytic hamartomas are normally a feature of tuberous
sclerosis and their presence should initiate a search for the
intracranial and cutaneous manifestations of this disease. This
syndrome has been linked to germline mutations involving the
genes TSCJ and TSC2 in which loss ofthe normal second allele
by a 'second hit' leads to hamartoma formation . These genes
apparently have a role in regulating cell and tissue size.
Inheritance is dominant with variable penetrance.

Fig. 17.73 This is a typical nodular white 'mulberry' tumour arising from the
superficial retina adjacent to the disc. Multiple lesions are not uncommon and can
sometimes be mistaken for a retinoblastoma in a child or for drusen of the disc in
adults. Intratumour calcification is common. The tumours can be observed to grow
slowly over many years.
By courtesy of Mr MD Sanders.

Fig. 17.74 This shows an early hamartomatous lesion in the peripheral retina of a child with tuberous sclerosis. It has a superficial
gelatinous appearance, beginning as a greyish opalescent thickening of the nerve fibre layer (left) that later becomes raised and pearly white
(right).
By courtesy Professor David Taylor.
 UP IIC DISC IN FILl RAIIONS AND I OM OURS

superficial
v ···· ' ·=~.::.,.,~----1 astrocytic
tumour

retina calcification

Fig. 17.75 Histological examination shows the tumour to be composed of

astrocytes derived from the superficial retina. Areas of bluish calcification
can be seen within the tumour.

Fig. 17.76 The cutaneous markers of tuberous sclerosis are adenoma sebaceum on the face (top left) and buttocks (bottom left),
periungual fibroadenomas (top right) and ash leaf patches of depigmentation on the body (bottom right).
NEUROFIBROMATOSIS TYPE II

leakage from
hamartoma hamartoma
vesse ls
late leakage
from disc

dilated superficial
ca pillaries from
papilloedema

Fig. 17.77 This patient presented with papilloedema and ataxia from a posterior fossa meningioma . He had no cutaneous abnormality
and no family history of neurological disease . A 'hamartomatous' lesion can be seen on the disc; it remained unchanged over 6 years of
observation. The raised intracranial pressure was due to a meningioma in the 4th ventricle .

Fig. 17.78 Several years after these

photographs of the optic disc were taken,
this patient complained of progressive
deafness and was found to have bilateral
acoustic neuromas, confirming a diagnosis
of neurofibromatosis type II. At this stage
the patient had developed multiple and en
plaque meningioma shown in this
gadolinium enhanced MRI.
Strabismus
Chris Hammond, Elizabeth Tomlin

Anatomy
Visual Acuity and Amblyopia
Diagnosis and Evaluation of Strabismus
Concomitant Strabismus
lncomitant Strabismus
Cranial Nerve Palsies
Myasthenia Gravis
Congenital Nystagmus
STRABISMUS

Strabismus is present when the foveas of both eyes are not
simultaneously aligned on the object of regard; for distance
fixation this means that the visual axes are not parallel.
Strabismus is classified by the direction of the deviation: if the
visual axes converge there is esodeviation; if they diverge there is
exodeviation. If the visual axes differ in vertical direction there
is hyperdeviation or hypodeviation, depending on whether the
eye described is higher or lower than its fellow. Strabismus may
be manifest- a 'tropia'-if the deviation is present with both eyes
open or latent- a 'phoria'- when the deviation is demonstrable
only with the eyes dissociated and binocular visual reflexes
disrupted. Strabismus is concomitant when the angle of
deviation remains constant (or nearly so) irrespective of the
position of gaze or the eye that fixates or incomitant when the
angle of deviation varies with the direction of gaze and fixing eye.
Incomitant deviations are generally associated with ocular
muscle paresis or mechanical restriction of rotation of the globe.

ANATOMY

Ocular posture is controlled by the six extraocular muscles, the
four recti and two obliques. Pulleys of connective tissue attached
to orbital bones and extraocular muscles form a fascial sling
around the globe which helps to maintain ocular position. The
rectus muscles arise at the orbital apex and insert anterior to the
equator of the globe. A useful way to consider the actions of the
extraocular muscles is to think of them as antagonistic pairs. Two
fundamental laws govern their innervation: Hering's law of equal
innervation states that an impulse to one muscle to contract is
accompanied by an identical impulse to the contralateral
synergist to contract and Sherrington's law of reciprocal
innervation states that an impulse to one muscle to contract is
accompanied by an identical stimulus to the ipsilateral antagonist
to relax.
Table 18.1 shows the primary, secondary and tertiary actions
of the extraocular muscles. Torsional movements are described as
intorsional or extorsional in relation to the midline.

superior rectus levator palpabrae

superioris

lateral rectus medial rectus

inferior rectus

Fig. 18.1 The extraocular muscles consist of two layers: a 'global layer' adjacent to the globe, and the 'orbital' layer peripheral to this.
(Left) Histology of the orbit of a 17 -month-old infant stained with Masson trichrome shows the extraocular muscles suspended in blue
orbital connective tissue. The orbital layer is more blue and the global layer more red. (Right) Higher magnification of the lateral rectus
muscle shows collagen fibrils interspersed in the outer orbital layer; these fibrils are contiguous with the collagenous muscle pulleys of the
orbit, explaining the layer's bluish histological hue .
From Demer JL, Oh SY; Poukens V. Invest Ophthalmol Vis Sci 2000; 41:1280- 1290.
 Actions of the extraocular muscles
Primary action Secondary action Tertiary action
Medial rectus Adduction
Lateral rectus Abduction
Superior rectus Elevation Adduction Intorsion
Inferior rectus Depression Adduction Extorsion
Superior oblique Depression Intorsion Abduction
Inferior oblique Elevation Extorsion Abduction

Pulley extends

Primary position Adduction

Pul ley
contracts

Fig. 18.2 Recent research has shown that the

extraocular muscles are attached by connective tissue to
'f-~~-<:::----J.B/--4~ Centre of the orbital septa just posterior to their insertion on the
rotational changes
globe producing a dynamic pulley system that is
believed to play an important role in positioning the
globe by interacting with the actions of the orbital
extraocular muscle layer. For example, on adduction,
the medial rectus pulley is displaced posteriorly and the
lateral rectus pulley anteriorly.
Reprinted with permission from Denser J F, Oh S Y, Poukens V.
Nasal Temporal Evidence for active control of rectus extraocular muscle pulleys.
Invest Ophthalmol Vis Sci 2000; 41:1280-1290. ©2000
layer layer Association for Research in Vision and Ophthalmology.

Fig. 18.3 The action of the two horizontal recti

is the simplest to understand as they work
around a common vertical axis. The action of the
vertical recti is more complex because they
attach medial to the vertical axis of the globe. As
a result they produce pure elevation and
depression only when the eye is abducted by 23°.
Either side of that angle some torsion is also
produced: in a more adducted eye the superior
rectus produces more intorsion and the inferior
rectus more extorsion. In addition, the vertical
recti have a horizontal component to their
. action.

40°
so·

Fig. 18.4 This demonstrates the primary,

secondary and tertiary actions of the superior
oblique muscle . In adduction the action of the
superior oblique is primarily depression, in
primary gaze it is cyclovertical, and in
abduction intorsional.
 VISUAL ACUITY AND AMBLYOPIA

Measurement of acuity (see Ch. 1) is critical in the assessment particularly if nystagmus is present. Testing acuity in children
and treatment of amblyopia and strabismus. It should be demands time and patience; the method depends on the child's
measured both binocularly and uniocularly, with and without development (Table 18.2).
correcting glasses and with and without associated head posture,

Table 18.2 Methods for testing visual acuity in children

Age or ability
Babies aged up to 9 months
Preverbal children
Verbal children
Pre-literate children
Literate children
Qualitative Quantitative
Binocular fixation Forced choice preferential looking cards
Fix and follow Visual evoked potential
Swinging test to suppress OKN
Tolerate occlusion and fixate w ith fel low eye
Hundreds and t housands
Cardiff cards
Kay's pictures
Sheridan-Gardiner singles
Sheridan-Gardiner linear
Sonksen Silver test
Snel len charts
Logmar acuity charts

Fig. 18.5 The Sheridan-Gardiner test requires recognition rather

than identification of letters and can be performed by cooperative
children by the age of 2- 3 years. The examiner has a flip-over book
of the various Snellen sizes and the child identifies the letter. The
main problem with this test is that acuity is overestimated because
of the crowding phenomenon when acuity is better for single
a letters rather than rows.
 VISUAL ACUITY AND AMBLYOPIA 607

BINOCULAR SINGLE VISION (BSV)

BSV starts developing by about 4 months of age in normal
infants; it combines the visual stimuli from each eye in a single
stereoscopic image. The advantages of BSV are accurate depth
perception (stereopsis), improved acuity compared with
uniocular vision, an enlarged field of vision, compensation for the
blindspot scotoma, and maintenance of ocular position.
Binocular vision can be divided into three processes:
simultaneous macular perception, fusion, and stereopsis. The
presence and quality of binocular vision needs to be assessed in
any patient with strabismus or diplopia. Most childhood
strabismus is associated with cortical suppression by which the
brain ignores the image of the deviating eye to avoid diplopia.
Strabismus that is acquired after the development of BSV usually
results in diplopia.

Fig. 18.6 The synoptophore can be used to assess the objective

and subjective angle of horizontal, vertical and torsional
strabismus. Each eye is dissociated and views an object that can be
moved into each of the nine positions of gaze to test simultaneous
macular perception, fusion, stereopsis and suppression. The
objective angle of strabismus is measured by making the patient
fixate each picture in turn and moving the tubes until there is no
movement of the eye on fixation. This can also be measured by
means of the prism cover test. The subjective angle is measured by
letting the patient move the tubes so that he can perceive, for
example, a bird in the cage. With normal retinal correspondence
the subjective and objective angles are the same . With abnormal
retinal correspondence the objective angle is the angle of deviation
but the subjective angle is 0°.

y
\ I \
//(( ~

\ ~
1-F

Fig. 18.7 To test simultaneous macular perception, different slides are presented to each eye (e.g. a bird and a cage) . The patient is then
asked to superimpose the images; for example, to put the bird into the cage. If the patient has no BSV, this will be impossible: the bird will
jump from one side of the cage to the other (across the patient's suppression scotoma). Sensory fusion is tested by getting the patient to
superimpose two images that are similar but have uniocular controls. For example, one eye sees a donkey with no tail and a carrot, the
other sees a donkey with a tail and no carrot. The tubes are converged and diverged until either the patient gets diplopia or one of the
uniocular controls disappears. A normal person has a broad horizontal fusional range of 306 eso to 15 6 exo and a narrow vertical range of
3° (Panum's fusional area). Diplopia is experienced outside these limits. Motor fusion is the ability to use both eyes to fuse similar images
through a range of vergences (i.e. convergence and divergence, fusional convergence will control an exophoria and divergence an esophoria.
It is usually tested with prisms but can also be tested on the synoptophore.
STRABISMUS

RE LE

Fig. 18.8 Fusion can be tested with the 20D prism test in small
children who cannot cooperate with the synoptophore. The
diagram shows a 20D base-out prism being placed in front of the
left eye so that the image is moved away from the fovea as the
patient fixates a small target. The left eye adducts to maintain
fixation. According to Hering's law, the right eye will abduct but
the child then appreciates diplopia and, to maintain BSV, makes an
adducting movement of the right eye to overcome the effect of the
prism.

Fig. 18.9 There are a number of tests for stereopsis that rely on
polarization or red-green goggles. The TNO test is a popular one in
which the patient views an apparently random pattern of red and
green dots through red and green glasses. The plates contain a
stereo image and with stereopsis a geometrical shape is seen
instead of the random pattern. This test has the advantage that it
does not involve dissociation of the eyes and still works in colour-
blind patients. Stereopsis is measured in seconds of arc; a person
with normal vision can fuse more than 60 seconds of arc disparity.
 VISUAL ACUITY AND AMBLYOPIA

A A A'

Fig. 18.10 Children with small-angle constant strabismus may develop an abnormal form ofBSV known as abnormal retinal
correspondence. (Left) This diagram of a small-angled constant right convergent strabismus shows an example of abnormal retinal
correspondence: the fovea of the left eye (FL) corresponds to the pseudo-fovea (P) in the right eye, with the fovea of the right eye (FR)
being suppressed when strabismus is of early onset. These patients tend to have some BSV despite their strabismus but there is usually mild
amblyopia in the deviating eye and worse than 120 seconds of arc of stereopsis. (Right) In a late-onset strabismus the fovea of the right eye
(FR) is not suppressed. The image falls at a point P in the right eye, it does not correspond to the fovea of the left eye (FL) and projects to
A'. This results in diplopia.

Fig. 18.11 Retinal correspondence is tested with Bagolini glasses

which have micro-striations that produce perpendicular streaks of
light perpendicular to each other in each eye when viewing a
spotlight. A cross of light is seen with binocular vision; in the
absence of strabismus this indicates normal retinal
correspondence. When a cross of light is seen in the presence of
strabismus this indicates abnormal retinal correspondence. If only
one streak of light is seen this is consistent with suppression. If the
patient sees two lights and two lines, diplopia is present. Worth
lights, seen through red and green goggles, work on a similar
principle.

AMBLYOPIA

Amblyopia is defined as deficient visual acuity in the absence of
structural abnormality of the eye or visual pathways. The
physiotogical basis is the lack of a clear focused retinal image
eventually leading to structural changes in the lateral geniculate
body and visual cortex. Although amblyopic eyes have reduced
acuity, they still retain normal colour vision, movement detection
and visual field; an afferent pupillary defect is found only when
the amblyopia is very dense. Amblyopia is classified into
anisometropic amblyopia due to unequal refractive errors;
strabismic amblyopia due to nonalignment of the visual axes and
least common is stimulus deprivation amblyopia due to ptosis,
cataract, etc., which can be the most difficult to treat. Visual loss
due to amblyopia can be distinguished from that due to other
causes by putting a neutral density filter in front of the eye; when
the cause is amblyopia acuity is maintained but other causes
result in reduced acuity.
 STRABISMUS

Fig. 18.12 The age at which treatment starts is critical to success: the younger
the child, the speedier the response and the better the prognosis for visual
improvement. Treatment usually has to be completed by 6- 7 years of age, when
the visual system matures. The mainstay of treatment is the correction of any
refractive error followed by occlusion of the eye with better visual acuity to
stimulate the amblyopic eye. The duration of occlusion and the length of
treatment depend on the child's age and response to treatment. Visual acuity
must be monitored carefully as there is a real risk of making the good eye
amblyopic (occl~sion amblyopia). Atropine occlusion is a reasonable alternative
for mild and moderate amblyopia.

DIAGNOSIS AND EVALUATION OF STRABISMUS

The majority of children with strabismus are otherwise entirely
healthy but a number of conditions are associated with a higher
than expected incidence. These include intrauterine problems,
prematurity and small-for-date babies, birth trauma, a family
history of strabismus and congenital abnormalities or cerebral
palsy. Strabismus is more common in children with debilitating
disease and may present after a severe illness or injury,
presumably from decompensation of a pre-existing phoria.
Strabismus is sometimes associated with other signs, the most
common of which is an abnormal head posture. When examining
for abnormal head posture it is important that the patient fixates
on a distant target . A cover test should be performed with and
without the head posture . Not all abnormal head postures are
adopted for ocular reasons (e.g. torticollis, vestibular disease,
habitual), but those that are usually help the patient to achieve a
limited area of binocular vision (Table 18.3). Occasionally a head
posture will be used to separate images or to fixate with a better
seeing eye.

Table 18.3 Causes of an abnormal head posture (AHP)

Head posture Ocular causes Direction Reason

Face turn Sixth nerve palsy Towards affected side Maintain BSV
Away from affected side Maintain single vision (separate images)
Nystagmus Either side Maximize acuity ('nu ll point')
Duane's syndrome Typical ly towards most affected eye Maintain BSV

Head tilt Fourth nerve pa lsy Away from affected side Maintain BSV
Hypotropia Towards lower eye Maintain BSV
Brown's syndrome Towards affected side Maintain BSV

Chin elevation or depression V exo pattern Chin up Maintain BSV

Bi lateral ptosis Chin up Maximize vision
Bilateral fourth nerve pa lsy Chin down Maintain BSV; avoid torsional diplopia

Fig. 18.13 It is extremely important to remember that

strabismus is also commonly the presenting feature of structural
eye disease . Most infantile strabismus is convergent. It is therefore
important to beware of a constant exotropia in an infant- this may
signify structural brain or ocular abnormalities. The most serious
example of this is shown by this child with strabismus and
leucocoria from a retinoblastoma. Exotropia is relatively common
in children with hydrocephalus, intellectual impairment and
inherited syndromes. Children presenting with an exotropia before
the age of 1 year require both ophthalmic and neurological
examination.
 DIAGNOSIS AND EVALUATION OF STRABISMUS

Fig. 18.14 Longstanding abnormal head postures of many years may cause secondary
skeletal abnormalities such as scoliosis or facial asymmetry. This woman has relative
maxillary hypoplasia associated with a congenital left fourth nerve palsy.

Fig. 18.15 Strabismus must be distinguished from pseudo-strabismus by demonstrating a manifest deviation on cover testing. Epicanthus
is by far the commonest cause of misdiagnosed convergent strabismus. (a) A false impression of convergence is given, particularly on
adduction, because the sclera is more covered medially. It should not be forgotten, however, that strabismus can coexist with epicanthus, as
demonstrated in (b). Other causes of pseudo-strabismus include a wide interpupillary distance, facial asymmetry, enophthalmos and ptosis.

Horizontal section
Lig ht reflex nasal
Nasal pupillary index

Visual axis
j ... ,. . .
------r--------)_1-----
Pupillary Angle
axis kappa

Fig. 18.16 Angle kappa is the angle between the visual axis and
the line perpendicular to the cornea. It occurs because the fovea
does not lie centrally on the anatomical axis but is usually slightly
temporal to it; this accounts for the slightly nasal displacement of
the corneal light reflex in a normal eye (normally about 4°). A
large positive angle kappa, as in this child, gives an impression of
divergent strabismus and a negative angle (which is unusual)
denotes apparent convergence. The only way to distinguish
between apparent and real strabismus is by a cover test. Angle
kappa is also of considerable importance in corneal refracture
surgery, which if centred on the pupillary axis can lead to post
treatment aberrations and patient dissatisfaction.
12 STRABISMUS

THE COVER TEST

The cover test is the fundamental method for assessing . (tropia) is present. No movement in the presence of an obvious
strabismus. Interruption of fixation of one eye causes the fellow strabismus indicates very poor acuity or mechanical restriction.
eye to move to fixate the same object if a manifest strabismus The alternate cover test detects latent strabismus (phoria).

Fig. 18.17 This illustrates a cover- uncover test on a child with right esotropia. The fixating left eye is covered forcing the right eye to take
up fixation (an interesting accommodative target should be used-a light is insufficient). On removing the cover the right eye does not hold
fixation and fixation is preferentially taken up by the left eye again. It can be inferred that the left eye has better acuity than the right eye.
The speed and accuracy of refixation gives information about the difference in acuity (faster with better acuity) and also shows the
direction and degree of strabismus.

Fig. 18.18 In this child fixation changes from the right to left eye following cover and persists on uncover. This is called alternation; it
signifies equal or nearly equal acuity in the two eyes.

Fig. 18.19 With latent strabismus (phoria) the eyes are straight but tend to deviate if binocular reflexes are interrupted. An alternate
cover test detects latent strabismus. In this patient with latent esophoria the right eye becomes convergent when occluded by the Spielman
occluder (this is a frosted occluder that is sufficiently opaque to blur vision but allows eye position to be seen through the occluder) . When
the cover is rapidly transferred to the left eye the right eye refixates and the left becomes convergent. The cover must be moved from one
eye to the other without allowing for refixation during the test; several passages are usually needed to dissociate the eyes fully and to reveal
the full magnitude of the deviation. Removal of the cover restores binocular vision and allows the rate of binocular recovery and degree of
control over the latent strabismus to be assessed. A cover-uncover test of each eye in turn should be performed initially to elicit a manifest
strabismus followed by the alternate cover test. Cover tests should be performed for near and distant fixation, with and without an
associated head posture, and with and without spectacles.
 DIAGNOSIS AND EVALUATION OF STRABISMUS

MEASUREMENT OF STRABISMUS

Fig. 18.20 In the prism cover test, a prism bar is used to increase the strength of the prism until there is no recovery m ovement on
alternate cover testing. This is equal to the deviation, expressed in prism dioptres (1 prism dioptre (L'.) = 'h 0 of angle) . The test should be
performed at 33 em and 6 m and sometimes at 60 m (for intermittent exodeviations). If spectacles are normally worn the test should be
performed both with and without them.

Fig. 18.21 Some patients because of age, disability or very poor vision in one eye, may not
reliably fixate for a prism cover test. Under these circumstances the angle of strabismus can
be estimated by noting the light reflex from a fixation light on the strabismic eye when fixating
with the fellow eye. This is termed the Hirschberg test; 1 mm displacement of the light reflex
equates to 1St. or 7° of strabismus; if the light reflex is at the limbus this equates to about 70L'.
of deviation.

Fig. 18.22 The light reflex may be centralized on the deviated

eye by prisms placed before the fixing eye. This is known as the
Krimsky test. Its disadvantage is that it measures only the manifest
component of the strabismus and does not take into account any
latent element, thereby tending to underestimate the angle .

EXAMINATION OF EYE MOVEMENTS

Duction refers to the movement of one eye, version to the opposite direction (convergence or divergence). The range of
simultaneous movement of both eyes in the same direction and eye movement, limitation of rotation, retraction of the globe,
vergence is the simultaneous movement of both eyes in the and abnormal lid movement must be assessed .

Fig. 18.23 Versions are observed as the child follows movement

of the target.
14 STRABISMUS

Fig. 18.24 Doll's head movements are induced by the brainstem vestibular-ocular reflexes (see Ch. 19) and are demonstrated by turning
the patient's head manually while the patient looks at the examiner's face.

Fig. 18.25 Vergences are assessed by asking the patient to fix a

target that is moved towards and away from the patient. The range
of convergence and divergence may be measured on the
synoptophore, with prisms or the RAF near-point rule
(accommodometer), as shown in this photograph. The near-point
of convergence is the distance at which diplopia is first appreciated;
the near-point of accommodation is when the text becomes
blurred.

CONCOMITANT STRABISMUS

Esotropia in otherwise healthy infants is associated with a in infants tends to be associated with ocular and neurological
positive family history and hyperopia; the risk appears to be abnormalities or syndromes involving intellectual impairment.
greater when both risk factors are present. Divergent strabismus

ESOTROPIA

Esotropia
I I
I
l r 1
I Primary
I I Secondary
II Consecutive
I
I
l 1
I Con stant
I Intermittent
I
l
I
1 l l I 1
INon-accommodative I I Accom mo dative
II Acco mm odat ive
I
Relat ing to
II Cyclic
:J:II Non specific
I
: fixat ion distance

I I
~ ~ ,l. ,l.
IFully accommodative I I Convergence excess I I Near
II Distance
I
Fig. 18.26 Classification of esotropia is important to make the proper management decisions.
 CONCOMITANT STRABISMUS

Fig. 18.27 Infantile esotropia (previously called 'congenital', although rarely p~esent from birth) is a large-angle alternating esotropia
presenting before 6 months of age. Infants usually cross-fixate: the left eye fixates objects to the right and right eye fixes to the left so that
amblyopia is rare. Care must be taken not to confuse infantile esotropia with bilateral sixth nerve palsies; abduction may appear limited,
but patching one eye or testing doll's head movements should show that abduction is actually intact. Infantile esotropia may be associated
with dissociated vertical deviation and latent nystagmus that develops later (at age 2-3 years). In latent nystagmus covering either eye
induces a manifest nystagmus with the fast phase towards the side of the uncovered eye; visual acuity also drops so that binocular visual
acuity is characteristically much better than uniocular acuity.

Fig. 18.28 Dissociated vertical divergence (DVD) is a phenomenon of unknown cause in

which the occluded eye deviates upwards and outwards, often with excyclotorsion of the
globe. On removing the cover the eye makes a recovery movement. The condition is usually
bilateral but may be asymmetrical: it is usually more marked when the eye with poorer acuity
is occluded. Common associations are infantile strabismus (usually esotropia) and latent
nystagmus. The left eye of this patient with DVD elevates under the semi-opaque Spielmann
occluder (this is very useful as both the occluded and the nonoccluded eye can be observed
simultaneously). On moving the cover to the right eye the left eye drifts downward to take up
fixation while the right eye elevates and extorts under the cover.

Fig. 18.29 A hyperopic patient needs to

accommodate to see distant objects clearly. This girl is
straight on distant fixation but breaks down to a left
esotropia for near vision (left). Spectacles with the full
hyperopic correction abolish the strabismus (right),
which is therefore a fully accommodative esotropia
that will be controlled by spectacles.
 Fig. 18.30 Strabismus that is only partially
corrected with the full hyperopic correction is
known as partially accommodative strabismus. It is
important to make sure that the full cycloplegic
correction is prescribed before labelling a
strabismus as partially accommodative. In these
cases the residual angle is assessed: if it is small,
cosmesis is often good and abnormal retinal
correspondence may develop; if the residual angle
is large and cosmetically unsatisfactory surgery
may be required. Surgery to correct the full angle
of strabismus without taking into account the
hyperopic spectacle correction will result in
exotropia of the patient still needs to wear their
glasses.

Fig. 18.31 Convergence excess esotropia occurs when accommodative effort results in esotropia or increased esotropia (i.e. the deviation
is greater at near than at distance). Convergence during accommodation can be measured by the AC: A ratio, the amount of convergence
induced by each dioptre of accommodation (expressed in prism dioptres per dioptre). A commonly used method to measure this is the
gradient method. A prism cover test is performed and the deviation is measured at 6 m with and without -3.0d lenses. These are assumed
to induce 3d of accommodation. The ratio is calculated by dividing the change in deviation by the 3d of accommodation. The normal range
is 2- 4 : 1; a high ratio indicates excessive convergence for a given amount of accommodation. This is of particular importance in planning
surgery.

EXOTROPIA
Fig. 18.32 Exotropia, like esotropia,
can be primary or secondary to poor
Extropia
vision or other ocular problems.
Consecutive exotropia usually arises in
patients who have had previous esotropia
l 1 1 with inadequate binocular vision, that
Primary L____s_e_co_n_d_a_ry____~l IL___c_o_n_s_e_cu_t_iv_e__~ allows the eye to drift out over time.
Patients with a consecutive exotropia
l 1 presenting for cosmetic strabismus
surgery must be assessed carefully using
Constant Intermittent
prisms and, if necessary, botulinum toxin

l I 1
to exclude loss of suppression in primary
gaze as surgery may result in constant
Near
IIL_____D_is_ta,n_c_e____~ll Non -specific diplopia. Intermittent exotropias are
relatively common and many people,
particularly myopes, have a divergence
l 1 excess exophoria that tends to manifest
L-------------~~
True s_im
L l_ _ _ _ __u_la_te_d____ ~ with tiredness or when unwell. Myopic
correction often helps .
 CONCOMITANT STRABISMUS

Distance exotropia Straight for near Patch 1 hour, unmasks exotropia for near

Fig. 18.33 This patient has a distance exotropia. A cover test indicates that the eyes are straight for near but not for distance . The
question is whether the lack of near deviation is due to its control by using the accommodation reflex. Clinically, 'simulated' and true
distance exotropias look identical; they can be distinguished by measuring the AC : A ratio or by occluding one eye for at least 1 hour to
eliminate fusion. A simulated distance exotropia will then decompensate for near when accommodation that has been controlling the near
deviation is relieved (high AC: A ratio) or when fusional stimulation is prevented. In true distance exotropia, which is less common, the
angle is unchanged despite interrupted accommodation and fusion and the AC : A ratio is normal. Differentiation of true from simulated
exotropia is extremely important when planning treatment.

A AND V PATTERNS

Concomitant deviations can show a difference in the horizontal
angle of deviation on changing from upgaze to downgaze,
resulting in an 'A' or 'V' pattern. These patterns may cause a
compensatory head posture in binocular patients. Minor degrees
of A and V phenomena are quite common. The aetiology is
complicated and may be due to abnormal positioning of
the oblique muscles on the globe, to abnormal positioning of the
horizontal and/or vertical recti muscles so altering their primary,
secondary and tertiary actions or to abnormal positioning and
function of the extraocular muscle-orbital pulley system.

Fig. 18.34 This girl has a manifest exotropia that increases markedly on upgaze in a V pattern. In addition, on horizontal gaze the
adducting eye elevates compared with the abducting eye, signifying inferior oblique overaction. Such a pattern could lead to a 'chin up'
head posture to maintain single vision. Bilateral inferior oblique muscle weakening procedures may be required in addition to horizontal
rectus surgery to correct the exotropia.
8 STRABISMUS

Fig. 18.35 This child has a marked V esotropia with right hypertropia in the primary position. This is probably the commonest type of A
orV deviation. On upgaze the eyes are almost straight but the esotropia increases in downgaze. On horizontal gaze both inferior oblique
muscles overact, the right more than the left. Such a pattern would lead to a 'chin down' head posture to maintain single vision. Even
where there is asymmetry it is advisable to weaken both overacting inferior obliques at the time of surgery.

Fig. 18.36 A patterns are less common than V patterns. This patient has an A-pattern exotropia following previous surgery. She is
divergent on depression but straight in the primary position, so there is no abnormal head posture. She has overaction of both superior
oblique muscles, more on the right than the left.
 INCOMITANT STRABISMUS

Fig. 18.37 This patient's eyes are straight in primary gaze and marginally divergent in downgaze with esotropia on upgaze. There is
bilateral superior oblique overaction, best seen by the down drift of the adducting eye in both right and left depression. The adducting eye is
also slightly hypotropic on right and left elevation (underaction of the inferior obliques).

'V' pattern

LRt

'A' pattern

MR t LR..j.
Fig. 18.38 V patterns can be improved by moving both medial recti (MR) down or the lateral
recti (LR) up. The converse will improve an A pattern. A V pattern can also be improved by
weakening the inferior oblique muscle.

INCOMITANT STRABISMUS

Strabismus is termed incomitant when the angle of deviation
between the visual axes varies with the position of gaze. This is
usually seen with palsies of the external ocular muscles,
myopathies or mechanically restricted rotation of the globes
although minor degrees of incomitance are also seen in
concomitant strabismus (e.g. A and V phenomena and
dissociated vertical deviation).
If incomitance is present cover testing in different directions
of gaze discloses its degree and allows the deviation to
be measured accurately. Evolution of diplopia needs to be
documented. Hess charts are based on the principle of Hering's
law of equal innervation of yoked ocular muscle pairs. If the
patient fixes with the paretic eye, 'more innervation' of the
normal yoke muscle occurs with gaze in the major direction of
action of the affected muscle so that the normal muscle in the
nonfixating eye overacts (i.e. with a left lateral rectus palsy the
right medial rectus overacts on left gaze). If the patient fixes with
the normal eye there will be corresponding underaction of the
affected muscle in the affected muscle's direction of gaze. This
can be documented by charting the eye movements. Hess charts
can be plotted with the patient wearing red-green goggles and
fixing each eye in turn; the 'smaller chart' belongs to the affected
eye. The Lees screen plots the same information but with a
mirror to dissociate the eyes. Hess charts provide good diagnostic
information and are excellent for following the evolution of
ocular movement abnormalities. The test cannot be performed,
however, if the patient has suppression of the image. Semi-
opaque (Spielman) occluders are useful to see the effect of
increased innervation in the unaffected eye's yoked muscle when
the eye with the paretic or restricted muscle tries to move into the
direction of action of the affected muscle.
Table 18.5 lists common causes of incomitant strabismus
classified by site of lesion.
STRABISMUS

Table 18.5 Common causes of incomitant strabismus classified by site of lesion

Site of lesion Exam ples Common causes
Internuclear Internuclear opht ha lmop legia Demyeli natio n, microvascular, t umour
Cran ial nerve palsies Third nerve pa lsy A neurysm (wit h pupil invo lvement), diabetes or microvascular (without pupil
involvement), t rauma (ofte n w ith sku ll fractu re), congenital
Fourth nerve palsy Congen ital, mi crovascul ar, trauma (deceleration injury),
Sixth nerve palsy Raised intracranial press ure, infl ammation (e.g. arteritis), trauma, tumour,
microvascu lar, demye li nation
Multiple crania l nerve palsies Orbita l apex lesio ns, cavernous sinus lesions, meningitis, intrinsic brainstem lesions
Neuromuscu lar junction Myasthenia gravis Ca n mimic almost any ocu lar mot ility problem (but does not effect pupillary action)
Muscular Thyro id eye disease, prog ressive external ophthalmoplegia, orbital myositis,
Orbita l Trauma Orb ita l blow-ou t f ract ure
Fibrosis Thyro id eye disease, sca rring from previous surgery (e .g. retinal detachment surgery)
'Musculofascia l' syndromes Brown's syndrome, Duane's syndrome

DIPLOPIA

Diplopia is the prime symptom of acquired incomitance and is
due to the images being projected to noncorresponding retinal
areas; two images are perceived provided there is pre-existing
normal binocular vision . Two symptoms can occur: visual
confusion and diplopia. Confusion happens if the foveas are
stimulated by two different objects. The images are projected to
the same point in space and are seen as either superimposed or
alternating images; this is rarely complained about . Diplopia is
always maximal in the direction of action of the affected muscle.
It is important to know whether diplopia is horizontal or vertical,
the direction of maximum separation, whether it varies with near
and distance vision or whether it can be improved by changing
head posture and whether it is constant or intermittent.
Appropriate directed questioning will help identify the paretic
muscle in many cases. Red-green goggles can be useful in
identifying the images from each eye.

Left gaze Primary posit ion Right gaze

Fig. 18.39 This diagram illustrates an incomitant strabismus from a right sixth nerve palsy. On left gaze the ocular axes are aligned and
there is n o diplopia . When looking straight ahead the right eye becomes slightly esotropic; the left fovea is stimulated as normal but the
target stimulates a nasal retinal point in the right eye resulting in diplopia. The angle between the two eyes increases on right gaze and the
images separate more. On cover testing the more peripheral image 'belongs' to the eye with the underacting muscle. Diplopia is always
maximal in the direction of action of the affected muscle. In this position, the image from the eye with the muscle palsy will always be more
peripheral because retinal projection is at its most disparate; it will also be less distinct as the retinal area being stimulated is less sensitive
than the fovea . For this reason patients occasionally cope with diplopia by adopting a head posture which produces maximal separation of
the images.
 INCOMITANT STRABISMUS 6

a Left eye Right eye

Temp.
: LatRec
La . Rct. e , R t. Md.R_::.,O-'--J--+-1---+Nasal : Me R t Mfd ect La R t.
L ' -- ::...· . -+-+-14 Temp.

<--- I . Rf<t Sp. bl 5 p bl I .R : r----

I~
l--; l-H

fJl! ~ m
''--I
t-
;• .I 7

b Left eye Right eye

Temp_
~
'\--\-----._

: Lat t~-
i s p.
uRI .R
1flff ~
i1 .0 I

t. M
:

R I '
'----1----

Nasal
c--- :

: M R I
....
;,
M
----·

=
L

""'
F=
:

R I
s
tl1tt
--
'l fff
"
t.R t ;
i--1-

Temp .
Fig. 18.40 These Hess charts show a
left sixth nerve palsy secondary to a
:
cavernous sinus aneurysm (the smaller
squares belong to the affected eye; one
small square is equivalent to 5°). Six
months later the sixth nerve palsy has
increased and there is now limitation of
the medial and superior recti, suggesting
early involvement of the third nerve.

Fig. 18.41 Another simple and useful method of monitoring a

patient's progress is to plot the field of binocular single vision with
the head fixed using an arc perimeter.

Fig. 18.42 Serial plotting of the field of binocular vision shows

improvement in the area of single vision in a patient with right
lateral rectus palsy after 2 months. Serial fields complement the
diagnostic information of a Hess chart as they give some idea of
0 Field of binocular fixation initial ly 0 Two months later the patient's functional visual field.
STRABISMUS

MECHANICAL (RESTRICTIVE) STRABISMUS

Incomitant strabismus are not always due to extraocular muscle
palsy. Every ocular movement requires coordinated contraction
of the agonist muscle and relaxation of its antagonist. Failure to
relax because of inflammation, fibrosis, adhesions or mechanical
interference by a space-occupying orbital lesion restricts ocular
motility. Two important signs to note in restrictive strabismus are
that ductions are equal to versions and that a traction test can
demonstrate tethering. Other signs are pain or discomfort and
globe retraction with movement away from the restriction and
that saccadic velocity is normal until the restriction is met, in
contrast to the reduced velocity seen with neurological or
myopathic lesions.

Duane's syndrome

Duane's retraction syndrome is congenital and usually unilateral,
although bilateral cases do occur. Various classifications exist but
it is easiest to think of cases as typical or atypical. In typical
Duane's syndrome, abduction of the affected globe is markedly
deficient (pseudo sixth nerve palsy). The palpebral aperture
widens on attempted abduction and narrows on adduction with
retraction of the globe. Adduction is normal or slightly limited.
In the atypical form, adduction is more limited than abduction,
resulting in exodeviation. Characteristic lid changes and globe
retraction on attempted adduction are found in all types of
Duane's syndrome. Some patients have up- or down-shoots of
the eye on adduction due to the fibrotic lateral rectus slipping
and tethering the globe. The condition is due to anomalous co-
contraction of the horizontal rectus muscles by aberrant
innervation of the lateral rectus from the third nerve; the
variations in movement can be attributed to varying amounts of
fibrosis in the lateral rectus and the degree of anomalous
innervation. A few cases are associated with other congenital
abnormalities such as the K.lippel-Feil anomaly, Goldenhar's
syndrome or exposure to thalidomide, suggesting that an insult in
neurogenesis at 6-8 weeks' gestation is responsible for the
syndrome.

Fig. 18.43 Patients may present with a compensatory face turn to the affected side or with an esotropia with suppression and amblyopia.
Ocular movements in a left Duane's syndrome demonstrate limitation of abduction with widening of the palpebral aperture. Left adduction
is associated with narrowing of the palpebral aperture and retraction of the globe. Surgery is rarely of value but is sometimes done for
abnormal head postures or large up- and down-shoots. Eye movements always remain abnormal and patient expectations must be realistic.

Brown's syndrome

In Brown's syndrome there is limited elevation in adduction of
the affected eye that simulates an inferior oblique palsy. It is
usually unilateral and congenital. Patients may present with an
abnormal head posture, tilting the head towards the unaffected
side to increase the field of binocular vision. On testing ocular
movements there is downdrift of the affected eye in adduction
and a 'click' may sometimes be heard or felt in the region of the
trochlea on attempted elevation. A traction test shows resistance
to elevation of the globe in adduction. In congenital cases the
usual aetiology is a short superior oblique tendon that is
restricted from passing through the trochlea; in acquired Brown's
syndrome, the tendon is either damaged by trauma (windscreen
injuries or ENT surgeons) or develops a nodule (rheumatoid
arthritis). Most children have binocular vision and tend to
improve with age. Surgery is reserved for cases where head
posture is cosmetically unacceptable.
 INCOMITANT STRABISMUS

Fig. 18.44 This child has a left Brown's syndrome with failure to elevate the left eye in adduction and downdrift of the eye on right gaze.

'Blow-out' fractures

Orbital fractures involve either the floor or medial orbital walls. contents to the walls. Fractures tend to occur where the walls are
A 'blow-out' fracture is generally caused by a direct blow to the thinnest: in the floor nasal to the infraorbital groove and in the
eye creating a pressure wave that transmits through the orbital medial wall in the orbital plate of the ethmoid bone.

Normal 'Blow-out'
anatomy fracture

Fig. 18.45 The normal anatomy of the

orbital walls can be compared to that
following a 'blow-out' fracture . Pressure
from a direct blow to the eye is
transmitted through the orbital contents
to the walls which fracture at their
thinnest place. Orbital fat, fibrous septa
Prolapse of fat, -1-- -- \ -- • \ and even extraocular muscle may become
fibrous septa trapped in the fracture, restricting rotation
and muscle of the globe. Intraocular damage is
common (see Chs 8, 11, 12 and 14).

Fig. 18.46 Lid and subconjunctival haematomas with no

posterior limit following blunt injury to the orbit suggest the
possibility of a blow-out fracture. In this patient blood has
accumulated forward from an orbital floor fracture site. Air may
enter the lids from the surrounding paranasal sinuses, especially on
blowing the nose, to cause crepitus on palpatation. In blow-out
fractures of the orbital floor the infraorbital nerve may be contused
and cause numbness of the cheek and incisor area of the upper jaw.
Intraocular damage should be excluded in every patient.
Fig. 18.47 This patient has a blow-out fracture of the right orbital floor. The right eye is slightly enophthalmic in the primary position. It
is restricted in its excursion in both attempted elevation and depressions. Tl:_J.e cause is usually not incarceration of the inferior rectus
muscle in the fracture site but trapping of the fibrous orbital septa connected to the inferior rectus. The patient has vertical diplopia with a
small central area of binocular vision.

h::;;,:,IW-.Jt-lr~i--=t'»"""f'i;;:>.-+-1 bony defect

--,L---{II{GHt-/1-.,{{Y,I---+--P;,L---+-----1 hematoma
~tf'--flil.-h::9JAd(C:::::___f-----i maxi llary sinus

/.,/-------"~~ll--:::1 displaced bony fragments

Fig. 18.48 Coronal computed tomography with bony windows is
--,'-----+--11-----1 hematoma
the investigation of choice to demonstrate the fracture and extent
of soft tissue displacement.

lfilfi
Left eye Right eye

~ ._
M
.R t
ilf.
M
I.

ec La
'
..

is
R t tR
'
t. :
·~

-
Temp .
s I .R t
:
~

· ·· ~
ftf! ..

\I
Fig. 18.49 Hess charts demonstrate the
restriction of movement. Their use is a
good way of demonstrating whether or not
ocular motility is recovering.
 Fig. 18.50 This patient, a Spanish bullfighter, was hit in the right
eye by the horn. He has gross enophthalmos, as can be seen from
asymmetry of the palpebral apertures. There was gross restriction
of horizontal movement. In most patients medial wall fractures are
less symptomatic because of the greater ability to fuse horizontal
rather than vertical disparity and the ease of compensatory head
movement.

Fig. 18.51 Computed tomograms of the same patient show

extensive fractures of the medial orbital wall with prolapse of the
medial rectus and orbital fat into the defect. Intraocular
examination showed a ruptured iris sphincter, angle recession and
retinal dialysis.

CRANIAl NERVE PAlSIES

THIRD NERVE PALSY

All but two of the extraocular muscles are supplied by the third
nerve and eyes with a total palsy have complete ptosis, internal
ophthalmoplegia of the pupil and ciliary muscle and assume a
downward and abducted position due to residual action of the
lateral rectus and superior oblique muscles. In this situation an
intact fourth nerve is demonstrated by eliciting intorsion of the
globe on downgaze . Partial third nerve palsy, in which some
muscles are affected more than others, is much more common.
This may affect the superior (superior rectus and levator) or
inferior (medial, inferior recti, inferior oblique, pupil, ciliary
muscle) division.
Table 18.6 lists features of third nerve palsy. Bilateral third
nerve palsy is rare and is usually seen with pituitary apoplexy or
uncal herniation from raised intracranial pressure and coning.

Table 18.6 Features of third nerve palsy

localization Diagnostic features
Nuclear Bilateral ptosis, contra latera l superior rectus palsy± mydriatic pupil
Fascicu lar Contralatera l hemip leg ia ±contralateral ataxia (superior cerebe llar peduncle)
Subarachnoid space All muscles± pupil sparing

Cavernous sinus Associated fourth, f ith and sixth nerve pa lsies, Horner's syndrome, aberrant regeneration, bilateral

Apex, orb ital Superior or inferior divisions ± proptosis

Fig. 18.52 Ocular motility in a patient with a left third nerve palsy. In the primary position the globe is divergent from the unopposed
action of the lateral rectus. There is absent adduction, elevation and depression of the left eye.

Left eye Right eye

~ ·1II!i
~ I
I is , i
: M . R ct. d " la . R l t. ct. ,
<- . . -+ Temp.
I p. bl. ~I ' ~'"" Fig. 18.53 The Hess chart of a patient
,::::;::::

f!f/1) .
~
: with a partial left third nerve palsy shows
underaction of the affected muscles and
corresponding overaction of the
contralateral synergists (owing to
Hering's law).
Fig. 18.54 Careful pupillary examination is mandatory in all patients. Pupillary dilatation with an isolated left third nerve palsy (left)
indicates compression by a posterior communicating aneurysm and a substantial risk of subarachnoid haemorrhage (see Ch. 19).
Emergency magnetic resonance angiography is required. An isolated left third nerve palsy in an elderly patient with pupil sparing (right) is
due to microvascular ischaemia (hypertension, diabetes, atherosclerosis); these patients do not require neuroimaging. Such palsies recover
spontaneously over 3-4 months. Both types of palsy can be painful.

Fig. 18.55 In some cases of third nerve palsy, particularly those due to trauma or chronic compression from aneurysms or meningiomas
and in some congenital cases, recovery of the palsy may lead to 'aberrant regeneration'. Aberrant regeneration is never seen with
microvascular lesions. In the absence of a history of these conditions (primary aberrant regeneration), aberrant regeneration is a feature of
slowly compressive cavernous sinus lesions. Typically there is constriction of the pupil on looking into the direction of gaze of the affected
muscle or lid elevation on downgaze (the pseudo-von Graefe sign) or adduction. This patient with a right third nerve palsy shows lid
elevation on attempted left medial gaze and downgaze.
8 STRABISMUS

FOURTH NERVE PALSIES

Fourth nerve palsies may be congenital or acquired and entities as they have different presenting symptoms, causes and
unilateral or bilateral; it is important to think of these as different clinical features (Table 18.7).

Table 18.7 Features of fourth nerve palsies

Presenting symptoms Aetiology Features
Congenital (unilateral) Decompensation of vertical phoria (any age) Lax or long superior Abnormal head posture
Head tilt to opposite side oblique tendon Vertical phoria or tropia
Birth trauma Extended vertical fusion range
Inferior oblique overaction
Positive BHTI
Facial hypoplasia
Acquired (unilateral) Vertical diplopia on downgaze to opposite side Young: blunt head trauma Abnormal head posture
Head tilt to opposite side Elderly: microvascular Vertical phoria or tropia
No extended fusion range
Inferior oblique overaction
Positive BHTI
Acquired (bilateral) Torsional diplopia on depression Severe closed head trauma Abnormal head posture (chin down)
AHP with chin depression Positive BHTI (bilateral)
Large V pattern
Bilateral inferior oblique overaction
Height reversal on lateral gaze (UR
on right gaze, RIL on left) > 10
degrees torsion (no fusion with prisms)

BHTI, Bielschowsky head tilt test.

Fig. 18.56 This patient has a left fourth nerve palsy. There is underaction of the left superior oblique on right depression and associated
overaction of the left inferior oblique on right gaze due to unopposed action.
 Left eye Right eye

Lf!ifi
Temp.t----t-t-1--+
~,_
M
<-- -
Rot
I f

M d
" "'
:

R ot
"
t. R ct
-
Temp_
Fig. 18.57 The Hess chart shows
underaction of the left superior oblique,
overaction of the left inferior oblique
W-+-1-t-r l-r~~~~-1-~~1 (unopposed ipsilateral antagonist) ,
C---J Sp bl I . R et.
overaction of the right inferior rectus

Vflj·· ~
(contralateral synergist) and underaction
of the right superior rectus (contralateral
-+ -- antagonist), indicating a longstanding
palsy with fully developed ocular motility
\ sequelae.

Fig. 18.58 Clues to a longstanding congenital aetiology are an increased vertical fusion range and old photographs showing a
longstanding abnormal head posture, as in this patient. Congenital palsies frequently decompensate to a manifest tropia. Patients have an
associated head posture tilting away from the side of the palsy; chin depression and a face turn to the opposite side are less consistent.
Hypoplasia of the face ipsilateral to the tilt may be present.

Fig. 18.59 In the Bielschowsky head-tilt test the patient is asked to fixate on a target at 3 metres and the head is tilted to each side
able 18.8). This stimulates intorsion of the inferior eye. If the superior oblique is weak, the superior rectus (the other intorter of
the ~obe) is unopposed and will elevate the eye to cause up-shoot of the affected eye, seen as increased vertical separation of
diplopia or increased hypertropia on cover testing. Here, a positive finding on a head-tilt test to the right confirms a right superior
oblique palsy. Note that the patient has an abnormal head tilt to the left in the primary position to compensate for this.
Table 18.8 Diagram of mechanism of Bielschowsky test in the presence of right superior oblique palsy
Tilting to the patient's right, the right eye
Superior oblique Intorts 0
Depresses 0
Superi or rectus In torts +
Elevates ++
Sum Elevation and intorsion of right eye
Tilt to th e rig ht stimulates compe nsatory intorsion of RE

Tilting to the patient's left, the left eye intorts

Superior rectus lntorts +
El evates +
Superior oblique In torts +
Depresses + Tilt to the left stimul ates co mpensatory intorsion of LE

Sum Intorsion and vertical position of left eye unchanged

Fig. 18.60 Bilateral fourth nerve palsies are almost invariably due t o severe closed
head injuries in which the nerve rootlets are ruptured by contusion as they decussate
superiorly over the midbrain; such patients usually have other serious neurological
damage. Patients have difficulty in reading and close work as the unopposed action of
the inferior recti on downgaze causes excyclotorsion of the globes. Patients may obtain
some benefit from a chin-down posture to reduce ocular depression. Symptoms are
often severe in the absence of gross ocular deviation and the condition is frequently
misdiagnosed as due to loss of BSV from head injury or compensation seeking.
Asymmetry is common and it is advisable to suspect bilateral damage in apparently
unilateral cases. Torsion needs to be measured on the synoptophore. This patient has
to maintain a marked chin-down posture to be able to read following a severe head
injury; note the tracheostomy scar.

Fig. 18.61 Bilateral fourth nerve palsies. Note mild underaction of both superior obliques in downgaze worse on the right than left.
There is some evidence of inferior oblique overactions, which can produce an alternating hypertropia on right and left gaze. The p atient
had 8° excyclotorsion in the left eye and 12° in the right eye. This can be corrected by laterally advancing the anterior fibres of the superior
oblique in each eye (the Harado- Ito procedure).
By courtesy of M r J Anderson.
SIXTH NERVE PALSY

Sixth nerve p alsy is the commonest neurological oculomotor bone as it turns forwards to enter the cavernous sinus. Patients
palsy; it may be congenital or acquired, unilateral or bilateral. present with horizontal diplopia that is worse on looking to the
The nerve has a long intracranial course. Palsy can be caused by affected side and often a face turn to the affected side to limit
pontine lesions (intrinsic brainstem lesions) or by subarachnoid, their diplopia in primary gaze. An incipient sixth nerve palsy can
cavernous sinus or orbital lesions. Sixth nerve palsy is seen as a present as a distance esotropia (divergence weakness) and should
false localizing sign with raised intracranial pressure when the be considered in any patient presenting with esodeviation greater
nerve is compressed against the apex of the petrous temporal for distance than near.

Fig. 18.62 This patient has a right sixth nerve palsy. Isolated sixth nerve palsies are common. In elderly patients they are often due to
microvascular ischaemia from hypertension, diabetes or arteriosclerosis; such patients require vascular investigation. The palsy usually
resolves over 3 months; in other patients and where the palsy does not resolve spontaneously, magnetic resonance imaging is required.
Temporal arteritis must be considered in any patient aged over 60 years and vasculitis in younger patients. Isolated palsies can also be seen
with multiple sclerosis and following viral illness in children.

Left eye Right eye

l
isup· R~

Temp.t- -+---1 -~ '"'

sp
lo>.R ,_,
rift
I_Q,

M•d R
-H
-":?\ __:- I-+ Nasal
11' 1f/t/
r-
-

'

:
Mel:!. R
1

Mid
I

ectla . R
I

Sp. ect
p.

t.R.
---+
~
-
e<t;

-
Temp_
Fig. 18.63 The Hess chart shows

~ '"I
~I Re t. J.S p. bl. ~I .R limitation of the left lateral rectus and

~··~ ' 7Jl!jl ~

overaction of the ipilateral medial rectus.
:
The eyes are convergent. With
longstanding palsy the deviation becomes
more concomitant with associated three-
'1 I muscle sequelae.

Fig. 18.64 Convergence spasm can simulate unilateral or bilateral sixth nerve palsy. The aetiology is nonorganic. Excessive convergence
limits the ability to abduct, diplopia is usually spasmodic (maintaining excessive convergence requires a lot of effort) and the clue to
diagnosis lies in noting pupillary miosis with the attacks.
32 STRABISMUS
COMBINED THIRD, FOURTH AND SIXTH NERVE PALSIES
Space occupying lesions involving the cavernous sinus are likely
to produce palsies of more than one oculomotor nerve owing to
the close proximity of the nerves. These lesions may present as a
progressive isolated sixth or partial third nerve palsy with
progressive involvement of other nerves. Cavernous sinus lesions
are often painful. Patients may also have involvement of the first
and second divisions of the fifth nerve, Horner's syndrome or
field loss from expansion up into the chiasm. Common causes
are invasive nasopharyngeal carcinoma, metastases,
meningiomas and aneurysms of the internal carotid artery.
Primary aberrant regeneration of the third nerve is pathognomic
of a slowly expanding cavernous sinus lesion (see Fig. 18.55).
Lesions at the orbital apex will also cause oculomotor palsies
with the addition of optic nerve signs; it may be difficult to
differentiate the neurological effects from the mechanical effects
of the lesion (see Ch. 20).
Fig. 18.65 Mucor mycosis is a rare cause of a cavernous sinus
syndrome, seen most commonly in diabetics with ketoacidosis and
rapidly progressive ocular motor palsies from obliterative invasion
of the arterial supply by the fungus. This patient has necrosis of the
hard palate.
By courtesy of Mr W A Green.
Fig. 18.66 This patient had a nasopharyngeal
carcinoma invading the base of the skull and
cavernous sinus. He has bilateral sixth nerve palsies
and bilateral third nerve palsies, more marked on
the right than the left. There is a right fourth nerve
palsy but the left fourth nerve is intact allowing
some depression and intorsion of the left eye.
 MYASTHENIA GRAVIS
Ocular involvement in myasthenia gravis is common being seen
in 70-80 per cent of myasthenic patients and is frequently the
presenting symptom. It can simulate virtually any ocular motility
abnormality but should be especially borne in mind when there
is variability or fatiguability of diplopia or when the pattern of
symptoms evolves over time. Ptosis and weakness of the
orbicularis are common but not invariable features but pupillary
involvement never occurs. Acetylcholine receptor antibodies are
present in only 70 per cent of patients with myasthenia restricted
to the ocular muscles. Patients require CT scanning of the chest
to detect a thymoma. The presence of striated muscle antibodies
also correlates with the presence of a thymoma. The Tensilon
(edrophonium) test has largely been superseded as a diagnostic
test because of the risk of respiratory or cardiac arrest by simple
fibre electromyography and other clinical tests such as a sleep or
ice-pack test. With a sleep test the motility defect is improved
immediately on wakening and with the icepack test ptosis is
improved by holding an icepack to the lid for 5 minutes.
Fig. 18.67 This patient presented with a
pseudo right sixth nerve palsy and bilateral
ptosis, worse on the left; the palsy
increased with fatigue .
 CONGENITAL NYSTAGMUS
Congenital nystagmus is present by 6 months of age. It has a
pendular horizontal waveform in primary gaze that becomes
jerky in eccentric gaze. Amplitude is the same in both eyes, it can
have a rotatory (but not vertical) component and patients do not
get oscillopsia. Various factors (Table 18. 9) affect the nystagmus:
it may have a 'null point' where amplitude is diminished which
can be exploited by assuming a certain head posture (usually a
face turn) to improve acuity when concentrating; it is dampened
by convergence so that patients may tend to hold objects close to
them. This improves reading vision and children can almost
always cope with normal schooling. They may sometimes develop
Table 18.9 Features of congenital nystagmus
• No oscillopsia
• Horizonta l or rotary, never vertical
• Pendular or jerky w aveform
• Null point, associated head posture
• Dampened by convergence
• Good near acuity
• Reversed by OKN
Table 18.10 Differential diagnosis of congenital nystagmus
Sensory deprivati on nystagmus
Ocular features Early onset; structural anterior, posterior
segment or optic nerve lesion
XL albinism
Investigations Ocular exam, ERG, MRI
* For exa mple, upbeaVdown beat , see-saw gaze evoked.
a variable esotropia (nystagmus blockage syndrome) using
convergence to suppress the nystagmus. Head shaking may
improve vision (spasmus nutans); and optokinetic stimuli
characteristically cause an 'inverted' OKN with beats in the
direction of the stripe.
Th~re are various types of congenital nystagmus (Table
18.1 0). In infantile esotropia latent nystagmus is seen on
occlusion of one eye with the fast phase beating away from
the occluded eye. This can become manifest if there is
sensory deprivation of one eye for some reason .
Sensory deficit nystagmus is due to visual deprivation
(e.g. cataract, ocular albinism, retinal dystrophy, optic
atrophy) and tends to develop by 2- 3 months of age,
sometimes accompanied by photophobia. Children with
retinal dystrophies frequently have a normal fundal
appearance at presentation and need electrodiagnostic testing
to exclude conditions such as Leber's congenital amaurosis.
Congenital idiopathic (motor) nystagmus is less common
and appears slightly later at about 3 months of age. Patients
have normal eyes and anterior visual pathways but reduced
visual acuity. Their developmental milestones are normal but
strabismus is common. There may be a dominant or X-
linked inheritance. The different types of congenital
nystagmus cannot be distinguished by waveform alone.
Congenital idiopathic nystagmus Nystag mus associat ed wit h
neu rologica l lesion*
Later onset , norma l eyes, normal Space-occupying lesions, metabol ic,
milestones, re latively good vision, neurodegenerative disease, trauma
can be inherited
Typica l: ni l Neurological exam, MRI, ERG, etc.
Atypical: neurologica l investigation
Neuro-ophthalmology
Gordon Plant, David Spalton

Ocular Movement
Anatomy of the Ocular Motor Pathways
Conjugate Gaze Palsies
The Pupil
Visual Field loss
Prechiasmal Field Defects
 OCULAR MOVEMENT
Signals that control ocular movement are initiated in the cerebral
hemispheres in a manner analogous to other motor neuronal
pathways. They are then transmitted to the gaze centres and
ocular motor nuclei in the midbrain and pons and leave the brain
in the third, fourth and sixth cranial nerves. Supranuclear
neuronal pathways conduct impulses to the gaze centres
internuclear pathways coordinate the gaze centres with the
ocular motor nuclei and the infranuclear pathways are the
individual ocular motor nerves. A great deal is known about the
organization of horizontal gaze control in the pons but less is
known about the midbrain mechanisms subserving vertical and
torsional ocular movements. Still less is known about the cortical
areas involved in ocular motor control but in recent years
considerable advances have been made. Horizontal and vertical
conjugate eye movements (i.e. movements of both eyes as a
yoked pair and mediated through supranuclear neuronal
pathways) can be divided into saccadic, pursuit and vestibular
movements, each of which has its own velocity and control
characteristics. Torsional mechanisms are active during conjugate
eye movements to prevent unwanted torsional movements
genuine torsional movements are seen mostly as ocular counter-
rolling during head tilt. These movements are conjugate in the
sense that as one eye intorts the other extorts but the associated
vertical movements are disconjugate as the intoning eye elevates
and the extorting eye depresses.
SUPRANUCLEAR GAZE CONTROL
Saccadic movements are rapid and relocate fixation of gaze,
either reflexly or voluntarily. They are initiated in the
contralateral premotor frontal cortex and, once initiated, the
movement is irrevocable and ocular position cannot again be
modified until the saccade has been completed. A saccade occurs
after a latent period of about 200 ms following initiation and has
a high velocity of up to 700°/sec. Saccades are tested clinically by
instructing the patient to look first at one stationary target and
then at another, or to look right and left or up and down with no
target present (see Fig. 19 .4).
Pursuit movements are slower and are concerned with
keeping the target at the fovea. They appear to be generated in
the ipsilateral occipital cortex but little is known about the
supranuclear pathway. Pursuit movements have a latency of
about 125 ms from initiation and a maximum velocity of less
than 50°/sec. The movement is smooth and modified
continuously according to the speed of the target if the pursuit
movement lags behind the target position a corrective saccade is
inserted to keep up. Pursuit movements are tested by asking the
patient to follow a slowly moving target. It is of great importance
that the target is clearly visible and that it is not moved too fast
(see Fig. 19 .5) .
Vestibular ocular movements are initiated in the semicircular
canals by head movements. They serve to maintain gaze direction
in space independently of head, neck and body movements and
have similar characteristics to pursuit movements, except that
they can reach much higher velocities. The vestibular ocular
reflexe_s (VOR) keep the horizon steady as we walk (our head
bobs up and down, the eyes moving in the opposite direction to
that of the head). In some circumstances this reflex has to be
suppressed as it would be impossible otherwise to follow a target
in space while the head is moving (e.g. to read on a train). In
most situations we make a combination of eye movements
directed to the target, head movements that are similarly
directed, and vestibular ocular movements that compensate for
any movements of the head that are not determined by the
motion of the target.
Vestibular ocular movements may be tested by a 'doll's head'
manoeuvre, in which the patient is asked to fixate on a target
while the examiner rotates the patient's head (see Fig. 19.6) . The
doll's head manoeuvre tests both the left and right labyrinths and
may be normal even if one labyrinth is totally nonfunctioning. To
test each labyrinth separately, caloric stimulation can be
employed which induces nystagmus by syringing the external
auditory meatus with cold or warm water. Recently a bedside test
has been described, based on the observation that the initial
component of a rapid head rotation depends upon the integrity
ofthe labyrinth towards which the head is turned (see Fig. 19.8).
Vergence movements are disconjugate and, although a centre
for convergence has been identified with reasonable certainty, it
is still not known whether a centre for divergence as such exists.
Vergence is tested by asking the subject to follow an approaching
target. Each type of conjugate movement should be examined in
both the horizontal and vertical axis. Precise recording of ocular
movement by electro-oculographic or infrared techniques has
contributed enormously to the understanding of the physiology
of ocular movements but careful examination of ocular motility
can supply all the information needed to make a clinical
diagnosis. Clinically dysfunction of the horizontal and vertical
gaze systems is frequently dissociated. It is helpful to examine
each type of movement in turn, in each axis, to decide whether
the problem involves either the horizontal or the vertical gaze
control or both systems. Most diseases disrupt saccadic and
pursuit movements initially with doll's head movements being
preserved until relatively late in the course of the disease. An
exception is vestibular failure (such as that following the use of
ototoxic drugs, e.g. streptomycin) where the vestibular ocular
reflex is selectively lost.
During examination of ocular movements it is important to
note whether the patient can hold a steady gaze in the primary or
eccentric positions (stability of fixation) and also the presence
and type of nystagmus, or spontaneous movements, in any
position of gaze.
 OCULAR MOVEMENT

Gaze Ocular motor Ocular motor

centres nuclei nerves

Fig. 19.1 The major inputs to the vertical and horizontal gaze
centres are saccadic and pursuit commands from the cerebral
hemispheres and the vestibular ocular reflexes from the vestibular
nuclei in the medulla . These impulses are then transmitted to the
individual ocular motor nuclei in the midbrain and pons.
Internuclear pathways coordinate the movements generated in the
gaze centres with each other and with the third, fourth and sixth
Supranuclear Internuclea r Intranuclear nerve nuclei. Excitatory impulses to an agonist muscle are
pathways pathways pathways accompanied by inhibitory impulses to its antagonist.

Fig. 19.2 Saccadic m ovements have been shown biomechanically

New position
of gaze to be generated by impulses in the form of a pulse and step. To
change eye position a rapid burst of neuronal signals (the pulse) is
Saccade
fired by the gaze centre and this rapidly moves the eye to the new
p osition. This rapid burst is integrated in the 'pulse-step generator'
(a neuronal complex within the gaze centre) to produce an
increased tonic discharge (the step) which holds the eye in its new
position. Similar responses take place in the agonist of the fellow
eye and reciprocal impulses relax the antagonist muscles. These
Step
changes are reflected by the EMG recording in an individual
Pulse step intergrator muscle. Neurophysiologically saccades are initiated by burst cells
in the paramedian pontine reticular formation (PPRF) which are
Pontine gaze centre inhibited from firing by pause cells at all times except during a
saccade. Thus the saccadic input suppresses the pause cell which
permits the burst cell to discharge immediately.

3 5,-------------------------,
Square wave jerks
Normal saccade New gaze Hypermetric saccade
position
Saccade

Primary position of gaze Back-to-back sacca des (ocular flutter if

horizontal opsoclonus if multi-directional)

Impu lse to muscle

2.-------------------------~

Hypometric saccade
6.---------~--------------,
Dysfunction of omnipause ce lls
with spontaneous discharge
of ocular motor neurones

4,-------------------------,
Slow saccade

Pulse duration short

with catch up saccade
- Ocular position
Gaze evo ked nystagmus inability
to maintain step ampl itude
Low pulse amplitude
- Neuronal signal

Fig. 19.3 The pulse-step generator exists physiologically in the horizontal gaze centre- otherwise known as the paramedian pontine
reticular formation (PPRF)-in the pons and various mismatches of the pulse to step signals have been shown to explain some types of
nystagmus and eye movement abnormalities seen in clinical practice.
 RO-OPHTHALMOLOGY

Saccades are examined by asking t~e

patient to look from one target
1
to another. 1 "
. ' I\

- '' ''
'' '' Fig. 19.4 Saccadic eye movements can be elicited simply by
''
asking patients to look right and left or up and down. This is a
useful strategy where the observation of large amplitude saccades
may reveal subtle abnormalities of saccadic velocity. An alternative
strategy is to ask patients to shift fixation from one target to
another, in this way saccades of large and small amplitude and
involving a variety of gaze shifts can be observed. The accuracy of
saccades (under- or over-shooting) can be tested. Slowing of the
velocity of saccades may be conjugate (as in a gaze palsy),
dysconjugate (as in a lateral rectus paresis or internuclear
Horizontal ly... ophthalmoplegia) or global (as in an ocular myopathy or some
forms of cerebellar disease) .

Fig. 19.5 When asking a subject to follow a target it is essential

that the target is clearly visible and is moved neither too slowly nor
To examine smooth pursuit movement the patient is asked to f ol low too rapidly. The reader should experiment by trying to follow his or
the target as it is moved in an arc her own finger as it is moved in a 180° arc from one side of the
head to the other at arm's length. A comfortable speed is about 30°
per seconds (6 seconds from ear to ear). Pursuit movements are
used to examine ductions and versions but, instead of looking at
the range of movement, we are now interested in the accuracy of
the following movement itself. The observer must watch for
saccadic intrusions which will indicate that the eye is not keeping
up with the target (in other words, there is reduced gain of the
smooth pursuit reflex). This is a universal finding in cerebellar
and vertically
disease .

The vestibule-ocular reflex is examined by asking the patient to fix on a

target while the examiner rotates their head
Vertically ..
Fig. 19.6 Vestibular ocular reflexes (VORs) are tested by asking
the patient to fixate a distant target (such as an acuity chart) and
then gently moving the patient's head from side to side or up and
down with increasing frequency until the patient reports movement
of the target or the subjective acuity falls, indicating retinal slip of
the image. Alternatively a retinal landm ark can be fixed using the
direct ophthalmoscope while the examiner rocks the head to and
fro. Loss of the VOR causes symptoms such as instability of the
horizon as the patient walks and is seen not uncommonly with
and horizontally
multiple sclerosis.

Fig. 19.7 Suppression of the VOR can be tested by asking the

?;~ )}········...
Keeps target fixed to body.
Eyes move in sa me direction
as head
Target clamped between teeth
patient to grip a target mounted on a spatula between the teeth
and to move the head from side to side or up and down with
increasing rapidity until the patient reports an inability to keep the
image 'still' or saccadic eye movem ents are observed as fixation is
lost and taken up again. The m echanism used to suppress the VOR
is the pursuit mechanism; if smooth pursuit is abnormal then so
will be VOR suppression, and vice versa. Patients who are able to
suppress their VOR complain of unusual symptoms such as
difficulty with reading when travelling.
 OCULAR MOVEMENT 63

Fig. 19.8 Only one functioning labyrinth is required for the tests described in Fig. 19.6 to be normal. Caloric testing can be used to
examine each labyrinth separately. Caloric reflexes are produced by stimulating th"e semicircular canals and vestibular nuclei with warm or
cold water and can provide useful information on the integrity of these pathways in the brainstem; this is especially useful in the
neurological assessment of brainstem damage in an unconscious patient. In a conscious patient cold water in the external auditory meatus
generates a nystagmus of both eyes with a fast phase to the opposite side but in unconscious patients the saccadic phase is lost and a tonic
deviation to the same side is seen. This indicates an intact pons but the results must be interpreted with caution after acute drug overdoses
when false-negative responses may be seen. Calories can be adapted to test vertical gaze (and therefore the integrity of the midbrain) by
syringing both ears.

Halmagyi's test

The patient is fixing The examiner rotates the patient's

the examiner's eye. head abruptly. Normal ly gaze
rema ins fixed.

Fig. 19.9 Unilateral labyrinthine function can be tested at the

W ith uni latera l vestibular
fai lure the eyes initially
move w ith the head.
There is then a saccade
to refixate.
bedside. If the head is rotated abruptly, the initial phase of the
VORis mediated by the labyrinth towards which the head is
turned. If that labyrinth is not functioning initially the eyes move
with the head and there is a corrective saccade as fixation is taken
up agam.

Fig. 19.10 The vestibular system responds only to acceleration

and slow head movements (less than 1° per second) stimulate the
optokinetic reflex (OKN). The hand-held OKN drum is useful as a
bedside test of the pursuit and saccadic systems. If there is a
saccadic palsy the eyes will deviate tonically in the direction of the
stripe movement: the pursuit mechanism has been elicited but
there is no saccade to return gaze towards primary position.
Turning the drum to the right elicits an ipsilateral pursuit
movement to the right and a contralateral saccade to the left. In
essence turning the drum to the right tests the right hemisphere
and vice versa to the left.
 ANATOMY OF THE OCULAR MOTOR PATHWAYS

a b Fig. 19.11 Saccades are generated in a number of

Cerebral hemispheres areas in the frontal premotor area of the contralateral
Su pplementary
Fronta l hemisphere including the frontal eye fields; thus a
eye field saccade to the right is generated in the left frontal
eye field
Superior lobe, passes through the anterior limb of the internal
parietal lobule
capsule and decussates in the midbrain to the
horizontal gaze centre in the pons. The incoming
<+..-\-f'r'r-- 1nferior visual information that controls smooth pursuit is
parietal lobule analysed in an occipitoparietal motion area. Pursuit
Striate movements are then generated in the ipsilateral
cortex superior parietal lobule so that a pursuit movement
to the right is controlled by the right hemisphere.
Dorsolateral Visual motion Little is known of the neuronal pathway, but the final
pref ronta l cortex areas common pathways for saccades and pursuit are the
conjugate horizontal and vertical gaze mechanisms in
the pons and midbrain. The inferior parietal lobule
may be concerned with shifts of attention, which
may also generate saccades.

nucleus of posterior
commissure
riMLF
"\tt'f7'-!.\=-'::--\~ Ill

IV
VI

Fig. 19.12 The final common pathway for all horizontal movements are the sixth nerve nuclei to which the PPRF, pursuit mechanisms
and vestibular nuclei project. Interneurones in the sixth nerve nucleus project through the medial longitudinal fasciculus (MLF) to the
contralateral medial rectus subunit of the oculomotor nucleus. For vertical saccades, the rostral interstitial nucleus of the MLF (riMLF)
projects to the third and fourth nerve nuclei . Vestibular inputs controlling vertical eye movements ascend from the lower brainstem to the
fourth and third nerve nuclei via the MLF. The nucleus of the posterior commissure projects on to both riMLFs and is particularly
important for upgaze.
 ANATOMY OF THE OCULAR MOTOR PATHWAYS

aqueduct
Ill nerve fasicules
Ill nerve
nucleus
red nucleus
Benedi kt's
syndrome
cerebral peduncle

Weber's
syndrome Ill nerve rootlets

Fig. 19.13 A transverse histological section of the midbrain at the level of the superior colliculus demonstrates the third nerve nucleus
inferior to the aqueduct with its efferent fibres. The medial longitudinal fasciculus (MLF) in connecting the third and fourth nerve nuclei
and contralateral horizontal gaze centres is responsible for coordinating horizontal and vertical movements. Infarcts in this region cause
Weber's syndrome (unilateral third nerve palsy and contralateral hemiplegia) and Benedikt's syndrome (unilateral third nerve palsy,
contralateral tremor and hyperaesthesia). (Stained to show myelin .)

The third nerve nucleus

Fig. 19.14 The third nerve nucleus is a complex assemblage of

1 Inferior rectus muscle
2 Inferior oblique muscle
3 Medial rectus muscle
4 Superior rectus muscle
5 Levator palpebrae muscle
6 Edinger-Westphal fibres to pupil
motor neurones. The parasympathetic nucleus (Edinger-Westphal
nucleus) of the pupil lies rostrally and superiorly. The inferior
rectus, medial rectus and inferior oblique muscles are all supplied
from ipsilateral subnuclei, but the superior rectus subnucleus is
contralateral. Both levator palpebrae muscles have a single caudal
superior nucleus. A complete 'nuclear' unilateral third nerve palsy
is therefore characterized by ipsilateral inferior oblique, medial and
inferior rectus weakness with bilateral ptosis and contralateral
superior rectus weakness .
2 NEURO-OPHTHALMOLOGY

floor of fourth
VI nerve
ventricle
nucleus

middle cerebellar medi al

peduncle longitu dinal
fasciculus
vestibular
nucleus VII nerve fibres

horizontal transverse
gaze centre vest ibu lar
connections
corticospinal
tracts

Fig. 19.15 A transverse histological section through the pons at the level ofthe sixth nerve nuclei demonstrates the medial longitudinal
fasciculus (MLF) and the centre for horizontal gaze (PPRF) . lnterneurones from the PPRF pass initially to the sixth nerve nucleus where
they synapse with the MLF (see Fig. 19.34). (Stained to show myelin.)

lateral wall of ~~~~.,----,r-="""''""""',.--..,-. intern al ca roti d

cavernous sinus arte ry

IV nerve 1-'-'-..;-;---7'---r.:< cut surface

V nerve f----'-":671'"-) of m idbrain

Fig. 19.16 The third and sixth nerves leave the ventral surface of
the brain and pass through the interpeduncular cistern before
entering the cavernous sinus. The sixth nerve passes almost
vertically upwards and bends forwards under the petroclinoid
ligament at the apex of the petrous temporal bone. Here it can be
compressed against the bone by raised CSF pressure or damaged
by fractures or disease in the bone (hence producing the sixth
nerve palsy associated with raised intracranial pressure). The fourth
nerve leaves the midbrain dorsally, decussates in the superior
medullary velum and passes through the subarachnoid space
around the midbrain between the superior cerebellar and posterior
cerebral arteries before entering the cavernous sinus.
 CONJUGATE GAZE PALSIES

Coronal section of the cavernous sinus

Optic tract

Fig. 19.17 In the cavernous sinus the third and fourth nerves lie
superiorly in the lateral wall; at the anterior end the third nerve divides into
superior (superior rectus and lid levator) and inferior (inferior and medial
rectus, inferior oblique, pupillary and ciliary muscles) branches. Sensory
fibres from the eye and forehead enter the cavernous sinus anteriorly in the
ophthalmic division of the fifth nerve, lying inferiorly in the lateral wall to
Internal carotid Sphenoidal
join the trigeminal ganglion at the posterior limit. The internal carotid
artery sinus
artery and sixth nerve lie within the sinus.

CONJUGATE GAZE PAlSIES

HORIZONTAL SUPRANUCLEAR PALSY

A horizontal gaze palsy results in an inability to make a conjugate lateral gaze with these tests depends on the integrity of the
ocular movement to one side and may result from a supranuclear pontine pathways and is preserved m the presence of a
or pontine lesion. These can be distinguished from each other by supranuclear lesion.
using 'doll's head' or caloric stimuli; the ability t o stimulate

Fig. 19.18 Following an acute cerebrovascular accident involving supranuclear pathways,

saccadic gaze is lost in the direction opposite to the side of the lesion and input from the
remaining hemisphere deviates the eyes towards the side of the lesion. (Occasionally,
irritative lesions, such as cerebral tumours or abscesses, produce deviation of the eyes to the
contralateral side.)

Fig. 19.19 (Left) On command the patient

is unable to make a gaze movement to the
target on his right. (Right) On doll's head
rotation to the left, however, the eyes deviate
fully to the right demonstrating intact
pontine reflexes and the supranuclear nature
of the lesion.
NEURO-OPHTHALMOLOGY

infarct

Fig. 19.20 ACT scan of the patient seen in Fig. 19.18, showing a large infarct in the
internal capsule due to the occlusion of middle cerebral artery branches, corresponding to
lesion 1 in Fig. 19.21. If the patient survives the acute ocular deviation recovers rapidly.
Horizontal gaze becomes full and saccades return to normal. This is probably due to a
restoration of control mechanisms by the superior colliculus.

Cerebral hemispheres

Fig. 19.21 A 'wiring diagram' shows that lesion 1 would result in

a right-sided supranuclear gaze palsy whereas lesion 2 destroys the
Q Horizontal gaze centre in pons pontine gaze centre producing a right-sided pontine gaze palsy.

VERTICAL GAZE PALSY

Vertical gaze palsies are caused by lesions in the area of the upper
midbrain and are less common. They produce a characteristic
triad of signs known as Parinaud's syndrome or the dorsal
midbrain syndrome: loss of vertical gaze and the pupillary light
reflex with preservation of the near reflex and the bizarre
movement abnormality known as convergence retraction
nystagmus. Vertical gaze is controlled from a centre in the
posterior commissure which integrates vertical gaze; there is a
downgaze centre caudal to the thalamus but isolated lesions of
this area are exceptionally rare. Most vertical gaze palsies affect
both upgaze and downgaze although small or early lesions in the
region of the posterior commissure tend to affect upgaze
preferentially; early lesions affect saccades only with preservation
of pursuit and oculocephalic (doll's head) movements. Lesions
compressing the midbrain may also obstruct the aqueduct
producing hydrocephalus and often papilloedema; lateral
extension may involve the optic radiations and posterior
extension produces ataxia from cerebellar compression.
Although tumours of the pineal gland are the most common
cause of Parinaud's syndrome, atherosclerosis, embolism,
vasculitis, demyelination or arteriovenous malformations may
occasionally be the causal factor.
 CONJUGATE GAZE PALSIES

Fig. 19.22 This elderly woman suffered a cerebrovascular accident in the upper midbrain . She retained the ability to make rapid and full
horizontal saccades.

Fig. 19.23 In the same

patient, voluntary up and
down gaze to saccadic
command is lost and
compensated for by head
movement. 'Doll's head'
rotation shows that
vertical movements can
be produced and that
pontine reflexes are
intact.

Convergence retraction nystagmus

Convergence
Fig. 19.24 Convergence retraction nystagmus is an interesting
ocular movement abnormality sometimes seen with vertical gaze
palsies. Bursts of convergence with retraction of both eyes into the
orbits are seen either spontaneously or on attempting an upward
saccade. These movements may also be accompanied by
accommodative spasm which accounts for the frequent complaint
of blurred vision. Convergence retraction nystagmus is shown
particularly well if the patient views a downward rotating Downward rotating drum
optokinetic drum which stimulates upward refixational saccades.
Fig. 19.25 In convergence retraction nystagmus the lesion is
thought to cause disinhibition of the ocular motor nuclei allowing
bursts of co-firing of the external ocular muscles. The medial recti
muscles are the most powerful of the external ocular muscles and
consequently the globes converge and retract into the orbits.
Fig. 19.26 Light- near dissociation of the pupils is the third sign of the triad of Parinaud's syndrome. The pupils are normally moderately
dilated and show a poor or absent light reaction but preserve the near reaction . It has been suggested that light reflex fibres are more dorsal
in the midbrain and are therefore selectively damaged by lesions in this area with comparative sparing of the more ventrally sited near reflex
pathways.

Fig. 19.27 Collier's sign is a bilateral retraction of the upper eyelids sometimes seen with acute upper midbrain lesions. This elderly man
was initially referred with a diagnosis of 'acute dysthyroid eye disease'. He had, in fact, suffered a cerebrovascular accident of the midbrain
region. Horizontal gaze was entirely normal but there was a partial vertical gaze palsy and retraction of both upper eyelids. The patient had
dubious long tract signs. The vertical gaze palsy and lid retraction rapidly recovered over 2- 3 weeks.

PROGRESSIVE SUPRANUCLEAR PALSY (STEELE-RICHARDSON SYNDROME)

This is a parkinsonian-like syndrome in which there is
extrapyramidal rigidity (especially of the axial muscles of the
neck, back and shoulders), pseudobulbar palsy, dysarthria and
dementia. There is marked postural instability and usually a
history of frequent falls predating the presentation with eye
symptoms by several years. Often difficultly with reading is an
early visual symptom. The importance of the diagnosis lies in
the poor prognosis: the disorder is unresponsive to treatment
and patients die in a relatively short time from progressive
neurological disease. This is in contrast to idiopathic
Parkinson's disease which with treatment is compatible with a
normal life expectancy with reasonably good mobility until the
later stages.
An early and diagnostic feature of progressive supranuclear
ophthalmoplegia is difficulty in making downgaze saccades with
preservation of horizontal saccadic movements and doll's head
reflexes. Initial loss of downgaze saccades is followed by complete
involvement of vertical, then horizontal, gaze. Saccades are lost
first, followed by pursuit movement, but doll's head reflexes are
preserved until late in the disease. Similar ocular movements can
be seen in children with neurolipid storage diseases such as sea
blue histiocytosis.
 Fig. 19.28 This patient can make an upward saccadic movement
but downgaze saccades are lost. She had extrapyramidal rigidity
and early dementia. Downgaze is present on doll's head movement,
showing the supranuclear nature of the lesion. Horizontal
movements are intact.

INTERNUCLEAR OPHTHALMOPLEGIA

Lesions in the medial longitudinal fasciculus (MLF) produce
poor adduction of the eye on the affected side and abducting
nystagmus in the contralateral eye; the ocular movements are
disconjugate, but patients rarely complain of diplopia. Normal
convergence demonstrates the integrity of the medial rectus
muscles, providing the lesion is not too dense (preservation of
convergence does not depend on whether the lesion affects the
anterior or posterior part of the MLF). The exact physiology of
MLF lesions is complicated and involves defects in pulse- step
generation of agonists and faults in reciprocal inhibition of
antagonists; excess tone of the lateral rectus of the abducting eye
may account for the nystagmus on abduction of that eye-
especially if the patient prefers to fix with the paretic eye. An
alternative explanation for the nystagmus in the abducting eye in
some cases is that the patient may also have a conjugate gaze-
evoked nystagmus that is not generated in the weakened medial
rectus.

poor adduction

Fig. 19.29 Bilateral internuclear ophthalmoplegia in young people is almost always associated with demyelination from multiple sclerosis.
Vertical nystagmus is usually present on upgaze and there may be a skew deviation. In this patient, the skew deviation alternates, there
being a left-over-right on right gaze and a right-over-left on left gaze. Subtle lesions can be demonstrated by asking the patient to make
rapid horizontal movements to show the slowness of adduction in each eye.
 - PHTHAlMOlOGY

incomplete adduction
from right internuclear
ophthalmoplegia

Fig. 19.30 Unilateral internuclear ophthalmoplegia is more frequently due to a vascular or ischaemic lesion as the basilar artery supplies
the pons by lateralizing perforating branches. This hypertensive patient shows a right-sided lower motor neurone seventh nerve palsy,
internuclear ophthalmoplegia and partial sixth palsy following a pontine infarct.

aqueduct IV ventricle

Fig. 19.31 The basilar artery supplies the pons by lateralizing

perforating branches. Occlusion of one of these produces an
unilateral INO.

Normal saccade
Overshooting
saccades
30
on refixation
t:
~ Fig. 19.32 In this recording of a right unilateral internuclear
0
i 30 ophthalmoplegia a 30° saccadic movement to the left demonstrates
slow adduction of the right eye and abducting nystagmus of the
0 ~ Slow saccade left. Return to the primary position shows normal saccadic
velocities in each eye but hypermetric overshooting saccades are
0 .5 1.0 1.5 2.0 seen, which are then corrected to hold the primary position of
Seconds
gaze. Such overshooting saccades are a common feature of
internuclear ophthalmoplegia and can be recognized clinically.
- Right eye - Lefteye By courtesy of Dr M Gresty.
 CONJUGATE GAZE PALSIES
D

Midbrain Medial
..------ longitudinal
fasiculus

Parapontine
reticular formation
(horizonta l gaze centre)

Fig. 19.33 A 'wiring diagram' shows that lesion 1 produces a

right unilateral internuclear ophthalmoplegia whereas lesion 2
causes bilateral internuclear ophthalmoplegia. Note that
interneurones from the PPRF pass into the sixth nerve nucleus and
synapse with interneurones that travel in the MLF to innervate the
Pons
contralateral medial rectus subunit of the oculomotor nucleus

THE 'ONE AND A HALF' SYNDROME (PARALYTIC PONTINE EXOTROPIA)

A more extensive unilateral lesion involving the horizontal gaze the '1 Yz syndrome' . In this situation, the only horizontal
centre and the medial longitudinal fasciculus (MLF) produces a movement that the patient can make is abduction of the
combination of a gaze palsy and internuclear ophthalmoplegia- contralateral eye.

Fig. 19.34 This patient with multiple sclerosis shows a right gaze palsy and right internuclear ophthalmoplegia, with only abduction of
the left eye on horizontal gaze remaining. Vertical movements were intact.
By courtesy of Mr M D Sanders.

Midbrain Medial longitudinal

..------ fasiculus

Para pontine
reticular formation
(horizonta l gaze centre)
Fig. 19.35 A wiring diagram shows that lesion 3 prevents
stimulation of the right PPRF producing a right pontine gaze palsy.
Impulses from the cortex to the left PPRF result in stimulation of
the left sixth nucleus and abduction of that eye but stimulation of
the right medial rectus through the MLF is blocked. Complete
'1 Yz syndromes' are uncommon but the combination of a partial
gaze palsy with partial ipsilateral internuclear ophthalmoplegia is
not uncommon and is readily observed by asking the patient to
Pons
attempt rapid horizontal saccadic movements.
 THE PUPIL

The smooth muscle of the pupil is innervated by the sympathetic
(dilator pupillae) and parasympathetic (constrictor pupillae)
muscles. Both pupils are normally of the same size although
small differences in diameter are seen in about 20 per cent of the
normal population and this is known as essential aniscoria.
Pathological aniscoria is caused by lesions affecting the
sympathetic or parasympathetic pathways or by local iris disease.
Lesions of the afferent visual system do not produce aniscoria,
that is sectioning one optic nerve will not alter pupillary size in
that eye.

Fig. 19.36 Sympathetic impulses are generated in the region of

the hypothalamus and transmitted down the spinal cord to synapse
at the ciliospinal centre in the lateral grey column. Pupillary
impulses leave the cord in myelinated preganglionic fibres at Tl
(some also at C8 and T2) and pass upwards in the sympathetic
Muller's muscles
Vasomotor and of eyelids chain to synapse in the superior cervical ganglion lying at the level
vasoconstrictor of the C 1 and C2 vertebrae. Nonmyelinated postganglionic fibres
fibres to face
form a plexus on the common carotid artery; vasomotor fibres to
External ca rotid the face leave on the external carotid artery at the bifurcation. The
artery internal carotid artery carries sympathetic innervation into the
cavernous sinus where the pupillary fibres join the nasociliary
branch of the ophthalmic division of the fifth nerve and enter the
eye by two or three long ciliary nerves at the optic disc to supply
the dilator pupillae muscle. Other sympathetic branches are taken
by branches of the ophthalmic artery to the lacrimal glands,
Muller's muscles and the orbital vessels.

Ciliary ganglion

Ill nerve

Lateral geniculate
body
Edinger-Westphal nucleus Superior bra chium

Fig. 19.37 The afferent pupillary light reflexes are

mediated through axons from ganglion cells in the
retina that pass back in the optic nerve and decussate
in the chiasm with the other visual fibres. The
pupillary fibres pass through the optic tract and
superior brachium to the Edinger- Westphal nucleus
of the third nerve; here, they synapse to produce a
lateral
simultaneous and bilateral response in each third
geniculate
chiasm nerve through interneuronal connections. Efferent
nucleus
parasympathetic preganglionic axons run forward in
each third nerve and pass into the inferior division at
the anterior aspect of the cavernous sinus to the
pituita ry third nerve ciliary ganglion, where they synapse to supply the
stalk nucleus constrictor pupillae by the short ciliary nerves. The
ratio of light fibres to accommodative fibres in the
third nerve is said to be 1 : 30.
r-:-------------------------------------------------------------------------------------------~T~
H~EPUPIL

RELATIVE AFFERENT PUPILLARY DEFECT

A relative afferent pupillary defect (RAPD) is an objective sign of
an asymmetrical lesion of the anterior visual pathway (retina,
optic nerve, chiasm or optic tract). A RAPD is seen with major
retinal lesions or neurological lesions of the anterior visual
pathway. Opacities in the ocular media, such as cataract, do not
produce a RAPD, but RAPDs may be seen with a dense vitreous
haemorrhage and small RAPDs with dense amblyopia. Thus, the
presence of a RAPD in the absence of gross ocular disease
indicates a neurological lesion in the anterior visual pathway; the
importance of this physical sign cannot be overemphasized as it
is an objective sign. Corroboration of a RAPD may be found in
asymmetrical loss of visual acuity, visual field, colour and
brightness sensation and optic disc pallor. Full neurological
investigation of such patients is mandatory in order to identify
treatable causes of visual failure.
Stimulation of one eye by a bright light produces an equal
constricting response in both eyes due to the direct and
consensual light reflexes; if the anterior visual pathway is
normal, transfer of the light to the fellow eye will maintain the
same constriction and tone on this pupil. However, if there is an
asymmetrical lesion in the pathway on one side (compression,
infarct, etc.), transfer of the light from the 'good' to the 'bad'
eye will result in less neuronal stimulation of the
Edinger- Westphal nucleus from that eye and a comparative
dilatation of both pupils, and vice versa. This is seen in practice
as an alternating constriction and dilatation of each pupil as the
light is swung from eye to eye. A RAPD and optic disc pallor
are the only objective clinical signs of disease of the afferent
visual system.

light is rapidly transferred

-...'-•"''"""""...., light is shone into left eye; to right eye, both
both pupils constrict pupi ls di late

Fig. 19.38 A right afferent pupillary defect is seen in this patient with retrobulbar neuritis of the right optic nerve. Stimulation of the left
eye produces bilateral pupillary constriction. Transfer of the light to the right eye produces a relative dilatation of the pupil in both eyes. If
one pupil is damaged or paralysed, an afferent pupillary defect can still be diagnosed by observing whether the size of the response varies in
the functioning pupil with alternate stimulation of the two eyes. The density of an afferent defect can be quantified by placing neutral
density filters of increasing darkness in front of the good eye until the pupillary responses are balanced.

Fig. 19.39 The 'wiring diagram' demonstrates the neurological

L R
basis of a RAPD. Stimulation of the normal left eye produces brisk
bilateral and equal pupillary constriction by the direct and
consensual light reflexes. Rapid transfer to the right eye, where
there is an optic nerve lesion, removes some relative input on the
Edinger-Westphal nucleus and both pupils dilate. Swinging the
light from left to right to left to right is the best way to
L R
demonstrate RAPD.
NEDRo-oPAfAALMOLOGY

ANISOCORIA

Anisocoria

Central pre gan glionic,

or
post gang li on ic lesion

3rd nerve palsy Adie's pupil I

Fig. 19.40 Flow diagram of differential diagnosis of anisocoria.

Posterior
communicating
artery

compresses -1~~~~
pupillary
vasa vasorum leading
fib res Ill nerve to infarct of central
nerve fibres
Fig. 19.41 In the interpeduncular cistern the third nerve passes
inferior to the posterior cerebral artery and lateral to the posterior
communicating artery. At this position the pupillary fibres lie on
the dorsomedial aspect of the nerve; they are readily compressed
by a posterior communicating artery aneurysm to produce a third
nerve palsy with pupillary dilatation. In contrast, vascular disease
such as diabetes or hypertension affects the vasa vasorum of the
nerve, infarcting central nerve fibres and paralysing the external
Third nerve palsy with pupillary dilation Third nerve palsy with pupil sparing
ocular muscles but sparing the pupil (see Ch. 18).

Giant internal
carotid aneurysm
Fig. 19.42 Two less common abnormalities of the pupil
associated with oculomotor nerve damage are illustrated here.
(Left) If the oculomotor nerve is compressed in the cavernous
sinus, for example by a meningioma or giant aneurysm of the
intracavernous carotid, there is often the combination of a
parasympathetic and sympathetic lesion of the pupil. The pupil is
midrange and neither dilates in the dark nor reacts to light. (Right)
Finally, with chronic compression there may be aberrant
reinnervation of the pupil, which will constrict when an attempt is
made to move the eye in the direction of action of one of the
muscles innervated by the oculomotor nerve (the drawing
illustrates the medial rectus) (see also Ch. 18).
 THE PUPIL

HORNER'S SYNDROME

Horner's syndrome is the result of a lesion in the sympathetic
pathway to the eye and may be due to a lesion in the central,
preganglionic or postganglionic neuronal pathways. The features
are of miosis and slight ptosis of the upper and lower lid on the
affected side; if the branches on the external carotid artery have
been affected there is a loss of facial sweating with acute lesions
and the facial and conjunctival blood vessels may be dilated.
Pharmacological testing can be used to diagnose and localize
the defect in Horner's syndrome but this has become of less
importance with the advent of magnetic resonance imaging
(MRI) which gives definitive information. The tests are, however,
important because they illustrate basic pharmacological
principles (Table 19.1). The diagnosis can be confirmed by
instilling G 4.0% cocaine in both eyes. This blocks the reuptake
of norepinephrine into the presynaptic vesicles. The pupils are
observed 15 min later the normal pupil dilates and eyelids retract
as reuptake of norepinephrine at the synapse is blocked by the
cocaine. The affected eye has no norepinephrine release to be
blocked and so the pupil size does not alter. Failure to dilate to
G hydroxyamphetamine which stimulates release of
norepinephrine from the presynaptic vesicles demonstrates a
postganglionic lesion as the nerve is already depleted of
norepinephrine; the importance of this is that preganglionic
lesions are often sinister and may accompany lesions such as a
Pancoast tumour of the lung.

Table 19.1 Pharmacological testing in Horner's syndrome and Adie's pupil

Drug Mechanism Normal pupil Central Preganglionic Postganglionic
Horner's syndrome
G cocaine Blocks reuptake of noradrenaline Dilates No change No change No change
G hydroxyamphetamine Blocks release of noradrenaline Dilates Dilates Dilates No change

Adie's pupil
G Ys% pilocarpine Postganglionic denervation hypersensitivity Normal pupi l, no change Constricts

retraction of eyelids

normal pupil dilates

Fig. 19.43 Miosis and ptosis are seen in the affected right eye of a patient with acquired Horner's syndrome. Some 15 min after a drop
of G 4.0% cocaine to each eye the left pupil dilates and the palpebral aperture widens but the right is unchanged confirming the diagnosis.
Subsequent failure of the right pupil to dilate with G hydroxyamphetamine 1-2 days later (after the effect of the cocaine has worn off)
would show that the localization of the lesion was postganglionic. Horner's syndrome does not produce more than about 2 mm of ptosis
which is due to involvement of Muller's muscles in the upper lid, involvement in the lower lid gives rise to 'upside down' ptosis.
 right Horner's
syndrome
normal pupil dilates
~21'jL79i"-:'---1 in the dark producing
increased anisocoria

Fig. 19.44 Horner's syndrome shows greater aniscoria in the dark than in the light as the affected eye fails to dilate . This can be useful as
a simple bedside diagnostic test.

ptosis ~
miosis
~
lighter iris

Fig. 19.45 Heterochromia is a feature of congenital or very

longstanding Horner's syndrome, the affected iris being lighter in
colour. Maintenance of melanin in the iris stroma (not the pigment
epithelium) is dependent on an intact sympathetic supply.

dissection of internal
carotid artery f-------"'-r>'~
at base of skull

Fig. 19.46 An acute painful Horner's syndrome may be caused by a

carotid dissection which can occur after minimal trauma in susceptible
individuals. This is an extremely important diagnosis to make as there
is a substantial risk of thromboembolism in the hours and days
following the dissection leading to a catastrophic stroke. The diagnosis
is made by requesting T 2 -weighted axial MR images of the skull base.
The scan shown here is of a patient who developed an painful Horner's
syndrome following a bout of vomiting.
PUPILLARY LIGHT-NEAR DISSOCIATION
A poor response of the light reflex with preservation of the near
response is a feature of Argyll Robertson pupils, Parinaud's
syndrome, Adie's pupils, aberrant third nerve regeneration or
severe bilateral visual loss with intact third nerves.
Adie's pupil is due to a lesion of the ciliary ganglion. In the
acute stage the pupil is dilated with an absent or poor light
reaction and loss of accommodation. Within weeks reinnervation
occurs but, as the majority of parasympathetic fibres passing
through the ciliary ganglion supply the ciliary muscle, the
majority of fibres that reinnervate the sphincter pupillae are
accommodative fibres. As a result when the pupil responds to
light only a few sectors will react; there will, however, be a
marked response to accommodation which is tonic, that is, the
pupil dilates and constricts more slowly than normal to
Fig. 19.47 Typical sectoral iris palsies seen in two cases of Adie's pupil. Constriction of the pupil to G 0.1% pilocarpine due to
postganglionic denervation hypersensitivity confirms the diagnosis.
By courtesy of Professor H S Thompson.
accommodation. The condition is frequently bilateral but may be
very asymmetrical. With time the pupil becomes miosed. Deep
tendon reflexes may be lost. Typical sectoral iris atrophy is seen
and is due to sectoral denervation of the iris sphincter following
the ciliary ganglion lesion. (This can be differentiated from
atrophy due to vasculitis as this tends to cause loss of the iris
pigment epithelium which remains unaffected in an Adie's
pupil.) Vermiform movements are helpful in confirming the
sectoral denervation of the pupil. These are best seen by setting
up hippus in the pupil on the slit lamp by directing the slit at the
pupil margin. A normal pupil does not change shape during the
rhythmic contractions of hippus: a sectorally denervated pupil
does change shape and the margin shows continuous rippling or
vermiform movements as the distortion occurs.
 ALMOLOGY
VISUAL FIELD LOSS
Advances in neuroimaging have made meticulous charting of
visual fields less important as an aid to topographical diagnosis of
neurological lesions affecting the visual system. Although
computed tomography (CT), particularly with contrast
enhancement demonstrates the majority of intracranial space-
occupying lesions MRI provides better anatomical localization of
lesions with more diagnostic information. Furthermore,
inflammatory lesions, such as seen in multiple sclerosis, are rarely
seen on CT but are readily visible on MRI. Gadolinium can be
used to show damage to the blood- brain barrier in a way
analogous to X-ray contrast medium.
Nevertheless, visual field assessment remains one of the
keystones of clinical ophthalmic diagnosis and accurate
documentation of fields is necessary in the evaluation and follow-
up of a wide variety of diseases. Carefully performed
confrontation fields provide good diagnostic information in many
neuro-ophthalmic cases but charting by one or other of the
standard methods is necessary to identify small defects or provide
brisk reaction
~i1t~P;........--1 preserved to
accommodation
Fig. 19.48 Argyll Robertson pupils are irregular, miosed and
asymmetrical in size with a poor light reflex and brisk near reflex.
They are the hallmark of neurosyphilis. However, similar pupils are
seen on very rare occasions in diabetics. The lesion is located in the
region of the Edinger- Westphal nucleus.
a permanent record. Where possible computer-assisted perimetry
is the technique of choice.
The majority of optic nerve fibres transmit information from
the central visual field (60- 70 per cent of optic nerve fibres
subserve the central 30 per cent of the field) and subtle and early
lesions are therefore usually found in the central field . Retinal
disease tends to produce colour loss in the blue-yellow axis
whereas optic nerve disease is associated with loss in the red-green
axis. There are numerous exceptions to this rule but it remains the
case that a red target is particularly good for detection of subtle
neurological field defects. The reason for the vulnerability of the
short-wavelength ('blue') cones in retinal damage is uncertain but
may relate to the low density of these cones compared to long-
('red') and medium- ('green') wavelength cones. In general retinal
and optic disc field defects are arranged about the horizontal
meridian, optic nerve lesions produce a central scotoma and
lesions in, or posterior to, the chiasm produce bilateral field
defects about the vertical meridian.
 VISUAL FIELD LOSS 6

Central retina l
Anterior communicating - ------,
artery
artery

Anterior cerebral Ophthalmic artery

arte ry

Hypop hysea l
artery

Posterior communicating /L__--r"::::::::;,(~lr'j;:-<c:f­

artery

Anterior choroi dal Fig. 19.49 A knowledge of the anatomy of the blood supply of
artery the visual pathways is essential in understanding the causes of
Basilar artery many types of field defect. This is derived from the internal carotid
(anterior and middle cerebral arteries) and the vertebral (posterior
Opti c tra ct cerebral arteries) with multiple areas of anastomosis between both
Lateral choroida l artery systems. These are particularly rich in the region of the chiasm,
optic tract and lateral geniculate nucleus so that infarcts in these
Lateral geni culate body
areas are extremely rare. The most common infarct of the visual
Poste rior cerebral artery artery pathways is an isolated lesion of the occipital cortex involving the
posterior cerebral artery. The anastomosis between this and the
Optic rad iation middle cerebral artery at the posterior pole of the occipital lobe
Visual co rtex
produces the typical macular sparing pattern of homonymous
hemianopia seen with lesions of this area .

PRECHIASMAL FIELD DEFECTS

Axons from the retinal ganglion cells converge on the optic disc;
they are divided horizontally by the horizontal raphe on the
temporal side but enter radially on the nasal side. Damage to a
bundle of axons at the vertical margins of the disc will produce
characteristic uniocular 'arcuate ' field defects (see Chs 7 and 17).
If this affects the superior or inferior optic disc margin the field
loss will occur below or above the horizontal meridian
respectively, producing an 'altitudinal' field defect. Compressive
and inflammatory optic n erve lesions tend to produce central
scotomas (see Ch. 1 7).
An interesting problem relates to the centrocaecal scotoma,
which extends from the fovea to the blind spot rather than being
pericentric around the fovea. The fibres that constitute the foveal
projection and the projection of the ganglion cells between the
fovea and the blind spot are sometimes referred to as the
'papillomacular bundle'. This is not a 'bundle' that can be
identified in normal anatomy; rather, there appears to be a
susceptibility of this group of fibres to nutritional and toxic
disorders and it is that has led to the identification of the so-
called 'bundle' in autopsy material.
The retinotopic arrangement of fibres in the optic nerve is not
as precise as has been suggested in anatomy texts. Nonetheless,
it is the case that fibres in three major groupings, those from the
upper hemi-retina, the lower hemi-retina and those forming the
centrocaecal proj ection , do not intermingle until decussation
begins as the chiasm is approached (see Fig. 19.50).
Optic nerve disease produces a group of typical physical signs,
no matter what the cause of the lesion (Table 19.2). The severity of
an afferent pupillary defect will depend on the density of the lesion
and degree of asymmetry of involvement in the two optic nerves.

Upper retin al Anterior Mid

fibres

Fig. 19.50 The retinotopic projection of nerve fibres in the optic

nerve. There is considerable intermingling of the axons in the optic
nerve and there is no precise topographic organization. However
Centroca ecal projection the centrocaecal fibres and the fibres from the upper and lower
hemi-retinae do remain distinct as shown above until decussation.
Lower retin al fib res The centrocaecal projection enters the nerve on its temporal side.
 RO-OPHTHALMOLOGY

Table 19.2 Signs and causes of optic nerve disease

Signs of optic nerve disease
Reduced acuity
Reduced colour vision
Afferent pupillary defect
Centra l scotoma
Optic disc changes (may be
normal, pal lor or swollen)
Causes of optic nerve lesions
Demyelinating disease
Compression
Ischaemia
Inflammation or vasculitis
Genetically inherited
Nutritional or toxic
Trauma
Neoplastic infiltration

a b

Fig. 19.51 Patterns of visual field loss with retinal, optic disc and optic nerve disease. Constriction of both visual fields (a) is seen with
retinal dystrophies (e .g. retinitis pigmentosa) and occasionally from optic disc disease (e.g. longstanding papilloedema). Altitudinal defects
(b) indicate optic disc disease, an inferior altitudinal defect is particularly a feature of anterior ischaemic optic neuropathy. (c) Centrocaecal
scotomas are a feature of toxic, nutritional and genetic inherited optic neuropathies. (d) Central scotomas are typically seen with optic
nerve lesions that are compressive or inflammatory rather than ischaemic.

Fig 19.52 Optic atrophy is an important physical sign that

always requires investigation and explanation. This patient
with a longstanding asymmetrical bilateral neuropathy from
sarcoidosis shows bitemporal pallor, more marked in the left
eye than the right (as well as myopic crescents).
 VISUAL FIELD LOSS

tempora l pallor of both optic

discs but worse in the right eye

nerve fibre loss less nerve fibre loss

Fig. 19.53 Loss of nerve fibres can be visualized in the retina. Destruction of nerve fibres in the anterior visual pathway (from the retina
to the lateral geniculate body) results in atrophy and loss of retinal nerve fibres about 6 weeks later. Nerve fibre defects are most easily
observed by using red-free light (see Ch. 7) and can be seen more easily in relatively pigmented fundi as in this patient with a pituitary
adenoma. Small defects appear as 'grooves' in the nerve fibre area, larger defects as areas of nerve fibre loss. Confirmatory signs of optic
nerve damage are found in a reduced visual acuity, reduced colour and brightness sensation, a relative afferent pupillary defect and
corresponding visual field defect.

THE CHIASM

Approximately 50 per cent of ganglion cell axon from each eye
(the nasal retinal fibres) decussate at the chiasm. On either side
of the vertical meridian the decussation is not absolute; and the
fibres of some nasal retinal ganglion cells do not decussate,
whereas some temporal fibres do. This may have a role in
strereopsis. Albinos have an interesting anomaly with a larger
percentage decussation, severely compromising the capacity to
develop binocular vision.
Field defects produced by chiasma! lesions (the commonest
lesions are pituitary adenoma, craniopharyngioma, suprasellar
meningioma or aneurysm) will depend on their relationship to
the anatomy of their chiasm. By far the commonest cause of
chiasma! compression is a pituitary adenoma with suprasellar
extension. In most cases these produce enlargement of the
pituitary fossa but plain skull radiography produces a high
incidence of false-negative results and its use as a screening test
is totally obsolete. All patients with a pattern of visual field loss
suggestive of chiasma! compression require MRI so that the
relationship of a mass to the chiasm and other neighbouring
structures can be demonstrated, usually with an accurate
identification of its pathological nature.
Elaborate attempts used to be made to correlate patterns of
field loss to different anatomical locations in the chiasm but
modern neuroimaging has rendered this exercise redundant.
There are, however, some simple principles that are useful in
clinical practice. Pure bitemporal hemianopias tend to be seen
following trauma, with pituitary adenomas or Rathke's cysts.
These hemianopias give rise to unusual visual symptoms such as
postfixational blindness and hemifield slide. Visual acuity may be
preserved until late and such patients are often thought to be
normal if visual field examination is not included in the visual
assessment. Patients with a combination of optic neuropathy and
chiasma! compression tend to present earlier because the
unilateral loss of acuity is noticed. In a patient with signs of optic
neuropathy it is essential to look for a defect in the other eye
(however minimal) which respects the vertical meridian as this
will indicate that the nerve is likely to be compressed
intracranially at the chiasm. Craniopharyngiomas tend to give
rise to complex patterns of field loss often with evidence of optic
nerve, chiasm and optic tract damage. Masses that do not
significantly elevate the chiasm are unlikely to cause visual failure
unless they are inflammatory in nature.

Fig. 19.54 Nasal retinal fibres (temporal field) decussate to the opposite optic tract, whereas
temporal retinal fibres (nasal field) remain uncrossed. Figs 19.57-19.59 relate lesions at sites 1, 2
and 3 to field defects.
0 NEURO-OPHTHALMOLOGY

Ill ventricle

Optic chasm

Fig. 19.55 The optic nerves exit from the optic canals at an
Posterior angle of about 45° to the horizontal and have an intracranial
clinoid course of about 15 mm. The chiasm lies about 10 mm above the
process roof of the pituitary fossa . It follows, therefore, that a pituitary
process
tumour must grow to a considerable extent above the fossa before
it compresses the chiasm.

Fig. 19.56 For this reason, patients with endocrine secreting

tumours, such as this patient with acromegaly, usually present
before they develop field defects whereas prolactinomas in men
and postmenopausal women or nonhormone-secreting
chromophobe adenomas commonly present with visual failure.

Fig. 19.57 A lesion on the outer lateral aspect of the tuberculum

sella, commonly a meningioma (lesion 1 in Fig. 19.54), may
compress not only the optic nerve on the same side but crossing
fibres from the other eye at the chiasm. This produces field loss
known as a 'junctional defect' : a unilateral central scotoma and a
superotemporal defect in the other eye caused by to a lesion at the
junction of the optic nerve and chiasm. It used to be thought that
this was due to crossing fibres looping forwards into the
"' contralateral optic nerve (Willbrand's knee) but this is now
£~ considered to be artefactual.

enhancin~
middle meningior
obliteration of
the suprasellar 1-+.,J..!;~~~·· : cerebra l I+H""-"o{
artery !ti~'"""hh~ basilar art
cistern
midbrain
posteriorr;,>,---,--o ;,.
cerebral
artery

Fig. 19.58 Enhanced computed tomography demonstrates a

suprasellar meningioma that produced this unusual 'junctional'
pattern of field defect. The patient also had a partial sixth nerve
palsy and a third nerve palsy with aberrant regeneration from
invasion of the cavernous sinus.
 VISUAL FIELD LOSS

Fig. 19.59 This diagram shows a typical superior bitemporal

field defect that would b e produced by a lesion at site 2 in Fig.
19.54 (a lesion at site 3 would produce an inferior bitemporal

I
"'"''"~ defect). The patient had acuities of 20/60 right and 20/80 left, a left
relative afferent pupillary defect, poor colour vision in both eyes
but worse in the left and bilateral optic disc pallor which was
'
g
greater in the left eye.

Blind temporal fields

overlap producing a
Fixation point scotoma posterior
to fixation

Fig. 19.60 Dense central bitemporal field loss produces the phenomenon of
postfixational blindness. If the patient focuses on a near object the bitemporal
field defects overlap producing a scotoma posterior to fixation. Patients find

CD that small objects disappear into this area and this produces interesting
symptoms; for example, an architect may have difficulty in putting a pencil on
a line or someone may notice difficulty in cutting their fingernail s.

Nasal field Nasal field

of right eye of left eye

Vertical phoria

Esophoria

Fig. 19.61 With dense bitemporal hemianopias there may

be little overlap between the remaining nasal fields to
produce enough binocular vision to control a phoria. This
may break down, often only transiently, causing diplopia in
the absence of an apparent ocular m otility defect. This
Exophoria phenomenon is known as hemifield slide.
2 NEURO-OPHTHALMOLOGY

Fig_ 19.62 Where crossing fibres are

Bow tie optic atrophy
predominantly affected and where there is also
extensive axonal loss a characteristic pattern
of optic atrophy can be seen. Temporal retinal
nerve fibres (nasal visual field) arch around
the macula and enter the disc vertically,
superiorly and inferiorly. Correspondingly,
although nasal retinal fibres (temporal field)
enter the disc around its entire circumference
but horizontally on both sides they enter the
disc without intermingling with temporal
retinal fibres. The 'bow tie' pattern of atrophy
results from exclusive loss of nasal retinal
fibres; the arcuate bundles superiorly and
inferiorly are thinned but still present while
there is total atrophy in a horizontal band
across the disc. This pattern is seen most
dramatically in cases of chiasma! transection;
- Nasal field axons - Temporal field axons the effects of compressive lesions are rarely as
selective as this.

lateral ventricle
Ill ventricle
chiasm
pituitary adenoma
....

Ill ventricle ~~
chiasm ~ -
pituitary adenoma ::
aqueduct ~

Fig. 19.63 T 1-weighted MRI is the investigation of choice to confirm the presence of a pituitary lesion. Scans should be performed in the
sagittal and coronal planes to define the anatomical boundaries of the lesion. The optic nerves and chiasm can be identified as anatomical
structures and the precise area of compression can be seen.

nodule protruding
into cavernous sinus
internal carotid artery

temporal lobe
pituitary adenoma

Fig. 19.64 In another patient the MRI scan shows a tumour extending into the
cavernous sinus. Asymptomatic extension into the cavernous sinus is quite common and
renders the tumour a more problematic surgical proposition. Occasionally pituitary
adenomas may present with ocular motor palsies.
 VISUAL FIELD LOSS

RETROCHIASMAL PATHWAYS

All lesions posterior to the chiasm must, by definition, produce a information on the localization of the lesion. It is important to
homonymous field defect. A complete homonymous hemianopia recognize that as macular fibres are represented in both visual
has no topographical localizing value in the absence of other cortices a complete hemianopia always leaves the patient with
signs but partial homonymous defects can produce diagnostic normal visual acuities.

OPTIC TRACT LESIONS

"'
!~

Fig. 19.65 Optic tract defects are uncommon and usually result from lesions causing chiasma! compression that extend posteriorly,
especially craniopharyngiomas or intrinsic gliomas of the chiasm. There is often a combination of optic nerve, chiasm and tract features.
Pure tract hemianopias may be seen with trauma, following surgery, congenitally and in multiple sclerosis. When incomplete, the field
defects are often incongruous (difference in size and density between the two affected hemifields); this arises because of the complex
anatomy of the lateral geniculate nucleus (see Fig. 19.67). There are two other useful signs which help to decide whether a hemianopia is
due to a tract or postgeniculate lesion. These are due to the fact that the nerve fibres are still retinal ganglion cell axons: therefore an
afferent pupillary defect is found in the eye with the temporal field defect. Secondly, although there will be bilateral disc pallor a
longstanding lesion will produce 'bow-tie' atrophy in the eye with the temporal hemianopia because the crossing fibres are affected.

tumour

Fig. 19.66 The patient presented with an asymptomatic complete right

homonymous hemianopia. Fundus-copy revealed a bow-tie atrophy in the right eye
(with the temporal hemianopia). Imaging showed a long-standing lesion (possibly a
hamartoma) in the region of the left optic tract/LGN/early optic radiation.
Fig. 19.67 Some 90 per cent of retinal ganglion cells project to the lateral geniculate nucleus (LGN); the remainder project to the
superior colliculus and the pupil centres in the midbrain. The LGN is a complex structure that is easiest to visualize in coronal section.
Centrally it is made up of six layers: layers 2, 3 and 5 receive the axons of uncrossed temporal retinal fibres and layers 1, 4 and 6 receive
the axons of the crossed fibres. The central part is concerned with macular vision, the medial part with upper retinal quadrants (inferior
field) and the lateral part with lower retinal quadrants, so that the representation of the visual field at this unique junction has been rotated
through 90°. Any point in the visual field is represented by a vertical column of cells passing perpendicularly through each lamina. Laminae
1 and 2 contain cell bodies with a larger diameter and are known as the 'magnocellular' layers, in contrast to the 'parvocellular' layers
superiorly. The magnocellular projection (10 per cent of cells) is concerned with movement detection, and the parvocellular (80 per cent of
cells) with colour vision and acuity. The remaining 10 per cent of cells pass through the interlaminar zones, known as the koniocellular
projection; these cells are of uncertain function. The LGN receives its blood supply from the anterior choroidal artery (a branch of the
carotid artery) and the lateral choroidal artery (a branch of the posterior cerebral artery) which anastomose on its surface. The dashed lines
indicate the extent of a lesion which would give rise to the field defect shown in Fig. 19.68 from infarction of the lateral choroidal artery.

Fig. 19.68 Lesions of the lateral geniculate nucleus are

excessively rare but can be diagnosed from the clinical features.
The LGN itself is difficult to visualize on imaging but its location
can be easily inferred as they sit atop the ambient cisterns. The
typical field defect is a wedge-shaped hemianopic defect that is
incongruous or alternatively has preservation of a central wedge in
each of hemianopic field. There is no relative afferent pupillary
defect as the pupillary fibres have already left to reach the third
nerve nucleus by the superior brachium but optic disc pallor is
seen because of damage to the retinal ganglion cell axons.

OPTIC RADIATIONS

After synapsing in the lateral geniculate body the visual fibres
pass posteriorly to the visual cortex on the medial aspect of the
occipital lobe; superior fibres carry inferior fields and vice versa.
The fibes become more tightly organized in their retinoptic
projection as they approach the cortex. For this reason,
posteriorly placed radiation lesions produce denser and more
congruous field defects. It is also important to realize that as the
damage is posterior to the synapse of the retinal axons in the
LGB, lesions in the optic radiation will not produce optic atrophy
(the only exception to this are rare congenital lesions when optic
atrophy can be seen from trans synaptic degeneration).
 VISUAL FIELD LOSS

I
Occipital pole
Fig. 19.69 These diagrams are taken from a study employing a
novel technique known as tractography where white matter
bundles can be 'virtually dissected' from MRI. The optic radiation
tract is shaped like an elongated 'S'. The optic tract fibres enter the
LGN anteroventrally and the optic radiation fibres leave
laterodorsally. The optic radiation fibres divide into a small ventral
D Splenium fibres temporal loop, which is now referred to as the Fleschig- Meyer
D Optic radiations loop, and the dorsal optic radiation. Feschig- Meyer's loop is
damaged in temporal lobe lesions because it loops forward towards
Optic tract the temporal pole and performs a hairpin bend around the
temporal horn of the lateral ventricle.

Fig. 19.70 It is unusual for temporal lobe lesions to produce a

field defect but if Fleschig-Meyer's loop is damaged an upper
quadrantic hemianopia will be produced, denser in the eye with
the nasal defect. Pure temporal lobe field defects must, by
definition, have normal pupillary responses as the pupillary axons

" '" "

have already separated from the visual pathway. However, the
temporal lobe and optic tracts lie in close proximity and share a
similar blood supply so it is not uncommon for temporal lobe

I
;:
8
'
lesions to involve the optic tracts. This would be shown by the
presence of an afferent pupillary defect in the eye on the side of
the lesion with pallor of both optic discs.

internal carotid arteries

high signal
from glioma

posterior communicating artery

compression of
cerebral peduncle posterior cerebral arteries

Fig. 19.71 An MRI scan of the same patient shows a glioma ofthe right temporal lobe.
 - PHTHALMOLOGY

Fig. 19.72 'Purer' examples of damage to Fleschig- Meyer's loop

are sec;:n following hippocampal resections for intractable epilepsy
due to hippocampal sclerosis, such as is shown here .

Left eye Right eye

Fig. 19.73 Inferior homonymou s quadrantanopias can occur following damage to the dorsal occipital lobe but may also occur with
parietal lobe lesions affecting the dorsal optic radiations. The pathway for the smooth pursuit component of the optokinetic reflex (OKN)
response projects from the parietal lobe ipsilaterally to the pons (see Fig. 19.11). In patients with hemianopia or inferior quadrantanopia
abnormalities of OKN may be used to demonstrate whether or not the parietal cortex is damaged. This is important as parietal lobe lesions
are frequently due to tumours whereas occipital lesions tend to be vascular. If the damage is purely occipital OKN will be normal; if it is
parietal then OKN will not be generated when the stripes are moving towards the side of the lesion as there will be no following response .
This can also be shown by carefully comparing pursuit of a target to left and right, when the OKN drum is rotated towards the side of the
lesion pursuit will be broken up by ' catch-up' saccades. The scan here shows a parietal lobe vascular malformation.

THE VISUAL CORTEX

The primary visual cortex is also known as 'striate' cortex owing designated as visual area 1, or 'Vl', because it is now recognized
to the fact that layer 4 is visible to the naked eye as a white stripe. that there are large number of separate visual areas of which VI
Large numbers of heavily myelinated LGN fibres terminate in is the primary receiving area for afferent information.
this layer. In recent years primary visual cortex has been
 VISUAL FIELD LOSS 6

Spleni um of
corpus cal losum

Macula extending
onto posterior surface
of occipital lobe
Posterior pole
-----r=-- - - - - - of left cerebral
hemisphere
Fig. 19.74 Vl lies mostly within the calcarine sulcus on the
Left Ri ght medial surface of the occipital lobe extending as far as the
occipitoparietal sulcus. The total length is about 5 em and
approximately half of this is concerned with central vision with the
macula itself being represented most posteriorly and extending on
to the hemispheric surface at the pole of the occipital lobe. The
outer temporal 30° of visual field of each eye is represented
uniocularly at the extreme anterior pole of the calcarine sulcus and
the representation of the horizontal meridian of the visual field
follows the apex of the calcarine sulcus with the lower contralateral
quadrant represented above this line and the upper quadrant
below it.

dilated horn of
--""~'!'7-.,.._-=~-----1 lateral ventricle
~P---,-c1IH-I'----1 infarct

~~-1:::---'i'-m~-----1 macular sparing

Fig. 19.75 The most common cause of an isolated homonymous hemianopia in the absence of other neurological signs is an occipital
lobe infarct from an occlusion in the posterior cerebral artery territory. Such patients often present to the eye department because they
have no symptoms other than loss of vision. These are frequently embolic and a cardiac examination is mandatory. The figure shows
sagittal (left) and axial (right) views of a right posterior cerebral artery occlusion. The patient had a complete hemianopia.
NEURO-OPHTHALMOLOGY

Fig. 19.76 If macular sparing is present (preservation of the

central 5- 10° of visual field from collateral circulation to the
occipital pole by the middle cerebral artery), this is diagnostic of
an occipital lobe lesion. Sparing of the outer temporal field in the
eye on the side of the hemianopia is also a feature of some
relatively localized occipital lobe infarcts and is due to unilateral
representation of the outer temporal field in the depths of the
calcarine fissure.

bilateral
cortical
infarcts

Re lat.lntens dB
1 0,0315 1S
2 0,100

.
3 0,315
4 1,00 0 0 113
0.40 4 I 114
b 0,50 3 II
0,83 2 Ill
'd 0,80 1 IV 16

' 1,00 0 v 54 - L1 - RJ

Fig. 19.77 A patient who suffers from bilateral posterior cerebral artery occlusion will be cortically blind. Recovery is often partial. This
patient had bilateral macular sparing, presumably because there was extensive supply of both occipital poles from middle cerebral territory.
Such patients are often considered to have a nonorganic visual loss because visual acuity, pupil reactions and fundus examination are
normal. Note that there is a vertical midline split preserved between the residual hemianoptic fields.

V7 D
D
V2
Fig. 19.78 Extra-striate visual cortex, previously grouped
D
V3 together as 'visual association cortex', is now known to be a rich
V5/MT 0 matrix of multiple representations of the visual field. Areas
MST D specialized for movement perception, colour vision, spatial
Vestibular cortex []
localization, face recognition and other visual submodalities have
Inferior parietal lobule D
Superior parietal lobule D been identified. This, much simplified, sketch gives some idea of
the complexity of these areas.
 VISUAL FIELD LOSS 6

infarcted right
fusiform gyrus
(includes area V4)

Left eye Right eye

Fig. 19.79 This patient cannot recognize faces- even

his own in photographs- (prosopagnosia) and has loss of
colour vision (cerebral achromatopsia) due to bilateral
ventral occipitotemporal infarction. Field defects were
bilateral superior homonymous quadrantanopias. Note
the field defect is dense and very congruous with a
vertical midline split.

occipitoparietal watershed infarction

T1 scan T2 scan

Left eye Right eye

Fig. 19.80 Another common clinical syndrome, because

it follows bilateral watershed occipitoparietal infarction, is
characterized by loss of visuospatial functions
(Balint-Holmes syndrome of visual disorientation). Such
patients cannot localize objects in space, for example,
objects in a photograph of a steet scene. Bilateral lower
homonymous quadrantanopias would be commonly seen.
Watershed infarcts commonly occur after severe
hypotension such as following a major haemorrhage or
anaesthetic hypoxia.
NEURO-OPHTHALMOLOGY

posterior enlargement of
lateral ventricle due to
central atrophy

cortical atrophy
more posteriorly

T2 weighted scans

Fig. 19.81 Balint-Holmes syndrome is also seen in a

variant of Alzheimer's disease where the process begins
posteriorly in the occipitoparietal cortex. Patients present
with difficulty in reading and subtle visual complaints but
often have normal acuity and visual fields early in the
process; the diagnosis is often delayed considerably.
The Orbit and -
Lacrimal System
Jimmy Uddin, Geoffrey Rose

Anatomy of the Orbit

Causes of Orbital Disease
Acute Proptosis
Chronic Axial Proptosis
Chronic Nonaxial Proptosis
Orbital Trauma
Enophthalmos
The Lacrimal Drainage System
Tests of Outflow Patency
Outflow Obstruction
2 THE ORBIT AND LACRIMAL SYSTEM

ANATOMY OF THE ORBIT

The orbit is conical with a volume of approximately 27 ml. It as a supportive cushion and fibrous septa run in planes between
contains the globe and the optic nerve, external ocular muscles, the ocular muscles and periosteum to support the orbital
ophthalmic artery and its branches, orbital veins and nerves and contents (see Ch. 18) .
the lacrimal gland. Orbital fat fills the remaining space and acts

Orbital plate
of greater wing Lesser wing Superior _,------- Frontal bone
of sphenoid of sphenoid orbital fissure
~---- Body of
sphenoid
Fig. 20.1 Periosteum covers the orbital bones and adheres firmly
_,-----~'---- Optic foramen
at the anterior rim and at the apex around the optic canal. It is
continuous with intracranial dura through the superior orbital
fissure and optic canal. The lateral wall of the orbit is formed by
the zygomatic bone and greater wing of the sphenoid. The frontal
bone and part of the lesser wing of the sphenoid make up the roof.
The fossa of the lacrimal gland lies superotemporally as a recess in
the frontal bone, just above the junction with the zygoma. The
floor is formed anteriorly by the maxillary process of the zygoma,
centrally by the orbital plate of the maxilla and posteriorly by a
,_- ---7"'-----------,--++-+- - Infraorbital small portion of the palatine bone. The infraorbital fissure lies
groove between the greater wing of the sphenoid and the orbital plate of
the maxilla and communicates with the pterygopalatine fossa
posteriorly. The infraorbital groove carries the infraorbital nerve
(Vb) and vessels. The medial wall is formed from anterior to
posterior by the frontal process of the maxilla, the lacrimal bone
(with the fossa of the lacrimal sac lying between), the ethmoid and
the body of the sphenoid.

Superior Sixth
orbital Lacrimal Frontal Trochlear Levator nerve
fissure nerve nerve nerve palpebrae Nasociliary
nerve
Superior rectus
muscle
Medial rectus
muscle Fig. 20.2 The superior orbital fissure lies between the greater
, ~-- Superior oblique wing of the sphenoid inferiorly and the lesser wing superiorly (see
muscle Fig. 20.1). The lacrimal and frontal branches of the fifth nerve, the
trochlear nerve and the superior ophthalmic vein are found
superiorly and external to the annulus of Zinn; the superior and
Oculomotor nerve: inferior divisions of the third nerve, the sixth nerve and nasociliary
,\I:J'I-F-+-'&-=---J±t-- - t - - - superior and nerve lie within the annulus. The optic canal lies in the body of the
inferior divisions sphenoid, medial and superior to the superior orbital fissure . It is
'-- ---1--.-- Ophthalmic lined with dura and transmits only the optic nerve and ophthalmic
artery artery which lies inferior to the nerve. Space-occupying lesions at
' - -+-- - Inferior rectus the orbital apex may compress the optic nerve and ocular motor
muscle nerves. Infiltrating lesions can spread through the superior orbital
Y - -- =-- Lateral rectus fissure into the cavernous sinus and middle cranial fossa to cause
muscle
pain and loss of sensation in the distribution of the ophthalmic
' -- ---'-"'- Inferior division of the trigeminal nerve . The sphenoidal sinus lies medial to
ophthalmic vein
the optic canal and the two are separated by extremely thin bone,
'-------:-=-'=-- Superior which may even be absent, so that the optic nerve is easily
ophthalmic vein
damaged by surgery or disease within the sphenoidal sinus.
 ANATOMY OF THE ORBIT

maxillary antrum

Fig. 20.3 The middle cranial fossa and temporal lobes lie
posterior to the orbit and are separated from it by the sphenoidal
wings. The temporalis muscles and fossa lie laterally and the
maxillary sinus lies inferomedially.
Fig. 20.4 Anatomical sections enable a clear correlation to be
made between the orbital anatomy and the computed tomography
(CT) appearance . Note the close relationship of the frontal lobes
to the orbital roof, the anterior and posterior ethmoidal sinuses to
the medial orbital wall and the sphenoidal sinus to the optic canal.

superior rectu s
~+-+f>--1--1 superior rectus
superior oblique rHhT-+n---"':;,L....:,:-'--~
o/--1\1---+---,i-+H optic nerve
lateral rectus
medial rectus
inferior rectu s

Fig. 20.5 CT scanning still has advantages over magnetic resonance imaging (MRI) in the orbit as the bony anatomy and calcification (an
important sign of many pathological processes) is readily seen on CT. Axial scans taken along the line joining the external auditory meatus
and inferior orbital rim cut the globe through the lens, optic nerve and optic canal in a single plane. The superior orbital fissure can be
mistaken for the optic canal, which lies medially and superiorly, adjacent and medial to the anterior clinoid process. The optic nerve has a
sinuous course within the orbit and cannot always be seen on a single cut if the section is thin. Similarly, partial sections of the ocular muscles
may resemble a space-occupying mass at the apex ifthe scan is not interpreted carefully. Coronal scans are frequently much more informative
and easier to interpret.
74 THE ORBIT AND LACRIMAL SYSTEM

optic nerve

ci liary gang lion

infraorbital nerve

Sympathetic
fib res to ocular Ill nerve parasympathetic
supply to iris and ciliary body

Ocular sensory
nerves fibres

Fig. 20.6 A dissection of the lateral aspect of the orbit shows the orbital lobe of the lacrimal gland and its nerve. The lateral rectus
muscle and sixth nerve are retracted to demonstrate the ciliary ganglion an d short ciliary nerves. The ciliary ganglion (b) contains not only
the synapses of the parasympathetic fibres to the iris and ciliary body from the third nerve, but also the efferent (and nonsynapsing)
sympathetic fibres to the ocular blood vessels. Afferent sensory fibres from the cornea, iris and ciliary body pass through the ganglion to the
nasociliary branch of the ophthalmic nerve.

ORBITAL BLOOD SUPPLY

Supratrochlear artery---- -- - - --------!.

Fig. 20.7 The ophthalmic artery arises

Anterior ethmoidal _ _ _ _ ___,.;...:;=-,::: from the internal carotid artery immediately
artery above the cavernous sinus and enters the
orbit through the optic canal inferior to the
optic nerve . It then passes laterally and
superiorly over the optic nerve to give
branches to the lacrimal gland and ocular
muscles. The ophthalmic artery continues
anteriorly and leaves the muscle cone to
anastomose with branches of the ext>et'll><i\
Posterior ethmoidal - - - -->+f
artery
carotid artery in the lids, face and scalp.
These anastomoses are of clinical importance
if the internal carotid system is occluded.
The two posterior ciliary arteries leave the
ophthalmic artery inferior to the optic nerve
at the orbital apex. They pass forwards and
divide before entering the globe around the
optic nerve as several short posterior ciliary
branches to supply the optic nerve head, retrolaminar optic nerve and choroid. The central retinal artery also arises from the ophthalmic
artery and passes forwards and inferior to the optic nerve, to penetrate the nerve some 10-12 mm posterior to the sclera (see Ch. 17).
The posterior and anterior ethmoidal arteries arise from the ophthalmic artery on the medial side of the orbit and enter the ethmoidal
sinuses near the level of the cribriform plate. The posterior ethmoidal artery lies just anterior to the optic canal and is an important surgical
landmark.
 CAUSES OF ORBITAL DISEASE

Dorsal nasa l Medial palpebral

artery artery

Supraorbital
artery Superior
ophtha lmic vein ! ! • '-+---- Supraorbital
vein

Ante rior Cavernous

ethmoidal artery sinus

Short poste rior

cilia ry artery

Muscular artery Long posterior

1-------AIIH- - - ciliary artery
Posterior
et hmoidal artery Lateral rectus
lli f - - - - muscle Pterygoid
pl exu s --------'..-----~-t-1

Ophthalmic _ _ _ _- - ! -.J4T
artery

Opt ic nerve -------'<•'\

Internal carotid Maxillary Inferior
~------- artery vein oph th almic vein

Fig. 20.8 The vortex veins from the choroid drain into the superior and inferior ophthalmic veins which flow into the cavernous sinus
posteriorly and the pterygopalatine plexus inferiorly. Apsidal veins join the superior and inferior ophthalmic veins in the orbit. Anteriorly
the orbital veins communicate with the frontal vein draining the scalp to form the facial vein which then drains into the external jugular
vein. Orbital veins do not have valves and the intracranial and extracranial venous systems communicate freely explaining the facility with
which infection can spread intracranially from the orbit. A distended superior orbital vein is seen as a neuroradiological feature of
caroticocavernous fistulas
Adapted from Snell RS, L emp MA . Clinical Anatomy of the Eye. © 1989 Oxford: Blackwell Scientific Publishers.

CAUSES OF ORBITAL DISEASE

Table 20.1 Causes of orbital disease

Children Adults
Orb ita l cell ulitis Trauma
Dermoid and epidermoid cysts Th yroid eye disease
Capillary haemangioma and lymphangioma Idiopathic orbita l inflammatory disease (formerly know n as 'pseudotum ou r')
Neurofibroma * Lacrimal gland inflammation and tumours
Rhabdomyosarcom a* Cavernous haemangioma
Optic nerve glioma * Varices and lymphangioma
Leukaemia * Lymphoma and lymphoproliferative disease
Meningioma (optic nerve or sphenoid wing)
Metastases
*Rare.
76 THE ORBIT AND LACRIMAL SYSTEM

Temporal is fossa Bone/suture Lacrimal gland Frontal sinus Fat and periocular
• Dermoid cyst • Dermoid cyst • Dacryoadenitis ·Mucocele connective tissue
·Fibrous • !OlD/lymphoma ·Sinusitis • Thyroid eye disease
dysplasia • Pleomorphic ·Tumours ·IOID
adenoma • Metastases
·Rhabdomyosarcoma
·Lymphoma
Eye
·Scleritis
•Intraocula r tumour extension
Ethmoid sinus
·Si nusitis
·Mucocele
·Osteoma
·Wegener's granulomatosis
·Tumour
Lacrimal sac
• Mucocele/dacryocystitis
·Transitional cell tumour
·Papilloma
Extraocular muscles
·Thyroid eye disease
·Myositis
Nasopharyngeal
·Malignancy
·Fu ngal disease
Maxillary sinus
·Sinusitis
•Tumour

Brain ----,-----\:--~
Absence of greater
wing of sphenoid

-~;;;;;;:;:;~;;:::::::::~---?=--+-11---- Peripheral nerve

Neurofibroma
Schwan noma
Cavernous sinus
Caroticocavernous fistula H +-+-- - -+ A - -----tL_ _ _ _ _ Metastastic infiltration
Th rombosis Breast
Carotid and ophthalmic artery - - - - Prostate
Aneu rysms Vasculitis Gastrointestinal
(e.g. Wegener's) Stenosis
r-t~t-r--.--.+-------l:--+--+------''<---- Muscle
Myositic
Optic nerve -----H-11-~_//'"'1111111•-IIIiii~~S-::~~ Thyroid
Glioma
Meningioma ~--f\-----1--- Venous/vascular
Capillary haemangioma
Cavernous haemangioma
Lymphangioma

Fig. 20.9 Orbital disease may arise from abnormalities of the normal constituents of the orbit, contiguous spread of disease from adjacent
structures, or invasion from haematogenous spread.

EXAMINATION OF THE ORBIT
A diverse range of pathology is found in the orbit and a careful
history is essential in all patients. The onset, duration and
variability of symptoms and the presence of pain, diplopia or
visual failure must be ascertained. The importance of
progressive symptoms indicating deterioration or an expanding
lesion cannot be overemphasized. Old photographs of the
patient are useful in dating the onset of long standing proptosis.
Many orbital diseases are related to systemic conditions (e.g.
neurofibromatosis, thyroid dysfunction, metastases) and a
history and examination for systemic disease that includes a
neuro-ophthalmic examination for associated intracranial
disease is obligatory.
Proptosis must be distinguished from pseudo-proptosis due to
enlargement of the globe, congenital bony deformity or facial
asymmetry, enophthalmos of the fellow eye and lid disease such
as retraction. Ptosis will occasionally present as 'proptosis' of the
contralateral eye (see Ch. 2).
Fig. 20.10 The degree of proptosis is measured with an
exophthalmometer. The feet of the instrument are placed on each
bony lateral orbital margin and the distance between the feet (i.e.
the distance between each lateral orbital rim) is recorded for future
comparison. The eye of the patient and that of observer are
aligned, corrected for parallax (the fellow eye must be occluded if a
strabismus is present) and the degree to which the corneal apex
protrudes in front of the lateral orbital margin is recorded.
Protrusion of the corneal apex varies with facial anatomy and so
there is no absolute normal value of proptosis although
asymmetrical proptosis of 2 mm or more is usually considered
significant.
ACUTE PROPTOSIS
Rapid onset of proptosis accompanied by pain and chemosis of
the conjunctiva is usually caused by infective orbital cellulitis or
idiopathic orbital inflammatory disease (formerly termed
'pseudo-tumour'). Less common causes are retrobulbar
haemorrhage, caroticocavernous fistula of acute inset or a rapidly
infiltrating carcinoma. In children, rapidly growing tumours such
as rhabdomyosarcoma and neuroblastoma may mimic orbital
cellulitis.
Orbital cellulitis is usually associated with an infected
adjacent sinus and requires careful management to prevent
ACUTE PROPTOSIS
Initial examination of a patient with orbital disease should
include optic nerve function (corrected visual acuities, colour
vision, visual fields, pupillary reflexes), ocular muscle balance
and movements, fundoscopy and retinoscopy. It is essential to
document proptosis, displacement of the globe and upper and
lower lid positions. Any mass should be assessed carefully for
location, colour, consistency, mobility and dynamic alteration.
Clinical evidence of spread of disease from the orbit into
neighbouring areas (or vice versa) should be sought, particularly
from the nose, sinuses, nasopharynx and cavernous sinus and
middle or frontal cranial fossa. Periorbital and corneal sensation
should be tested.
CT is the initial investigation of choice for most orbital
diseases. Ultrasonography is useful to distinguish cystic
(echolucent) from solid lesions (echogenic) quickly and to
demonstrate blood flow. MRI is the investigation of choice for
optic nerve disease.
Fig. 20.11 Variation in ocular position and pulsatile proptosis
should be sought where appropriate. Proptosis is axial if
displacement is along the visual axis and nonaxial if displacement
is off the visual axis. This can be judged by placing a clear plastic
rule horizontally across the bridge of the nose to measure the
horizontal and vertical positions of the visual axis of each eye. The
fellow eye should be occluded when strabismus is present.
permanent visual impairment, ocular motility problems or the
disaster of cavernous sinus thrombosis. It is important to
differentiate preseptal cellulitis, usually associated with lid
infection, from the potentially much more serious postseptal
orbital involvement. Restricted ocular movement and proptosis
are features of the latter. Chronically obstructed drainage of a
parana sal sinus can cause sterile accumulation of mucus, chronic
sinus enlargement and formation of a 'mucocele' which may
encroach into the orbit displacing the globe.
8 THE ORBIT AND LACRIMAL SYSTEM

Fig. 20.12 Acute orbital cellulitis presents with fever and

malaise, pain, proptosis, restriction of eye movements and
conjunctival injection and oedema. This girl has an acutely swollen
and painful left upper lid with the globe depressed from cellulitis in
the superior part of the orbit secondary to a frontal sinusitis.
Patients require hospital admission, nasal and blood cultures and
intravenous antibiotics. These should not be delayed for
investigations such as imaging. An orbital or subperiosteal abscess
generally requires surgical drainage .

bony defect
opacified
ethmoid sinus

subperiosteal
abscess

Fig. 20.13 CT scan from another patient showing an infective

extension from the ethmoidal sinus into the orbit with a small
subperiosteal abscess elevating the periosteum.

left proptosed globe opaque posterior ethmoids

distended su perior opaque sphenoid sinus

op hthalmic vein with fluid level

Fig. 20.14 Cavernous sinus thrombosis is now a rare complication of orbital cellulitis but must be considered when clinical signs
progress rapidly with associated meningism, ocular motor and pupillary palsies, and signs of acute inflammation in the cerebrospinal fluid.
MRI shows the thrombosis in the cavernous sinus better than CT.

Fig. 20.15 Embryonal sarcomas are tumours of mesenchymal
cells with the potential to differentiate into striated muscle (striated
or nonstriated rhabdomyomatous differentiation). They are
commonly known as rhabdomyosarcomas although they do not
arise from striated muscle. They are the commonest primary
orbital malignancy of childhood. They can grow very rapidly; this
child's proptosis increased almost daily.
CHRONIC AXIAL PROPTOSIS
Axial proptosis results from a lesion within the external ocular
muscle cone and is caused by a benign or malignant expansion of
THYROID EYE DISEASE
The commonest cause of axial proptosis is thyroid eye disease
which can affect the orbits symmetrically or asymmetrically, with
the latter producing apparently uniocular proptosis. Patients may
be hypothyroid, euthyroid or hyperthyroid. T3, T4 and thyroid
autoantibodies should be measured in all patients but about 15
per cent of patients have completely normal findings; in these
patients the diagnosis is made clinically and by CT. Patients
should be assessed for cosmesis, corneal exposure, diplopia and
CHRONIC AXIAL PROP I
Fig. 20.16 CT scan showing a mass in the region of the medial
rectus. Mter diagnostic biopsy treatment with radiotherapy and
chemotherapy carries an excellent prognosis provided the tumour
is confined to the orbit. These lesions can invade the orbital walls
and metastasize haematogenously to the lung, lymph nodes and
bone marrow.
one of its normal constituents or a metastasis from elsewhere.
optic nerve involvement, all of which may occur independently of
each other. Patients may have sore, irritable or watery eyes from
exposure keratopathy, superior limbic keratitis (see Ch. 5) or
disturbance of tear film metabolism. Smoking has been shown to
be a significant risk factor for the development of dysthyroid eye
disease which may also deteriorate at the time of treatment of
hyperthyroidism with I 13 1 .
Fig. 20.17 Pathologically, dysthyroid eye disease affects the
external ocular muscles rather than their tendinous insertions in
contrast to idiopathic myositis. In the early stage inflammatory cells
infiltrate the muscle belly causing oedema; as the disease
progresses, collagen and glycosaminoglycans are produced by
endomysia! fibroblasts. Chronically, the muscles become fibrotic
from contraction of the collagen and infiltrated by fat and may be
expanded by up to eight times their normal size.
By courtesy of Dr R Eagle.

Fig. 20.18 Axial and coronal CT scans demonstrate thickening of the extraocular muscles. The medial and inferior recti are preferentially
involved. Note that the muscle tendons are spared.
Fig. 20.19 Acute dysthyroid eye disease is associated with
conjunctival chemosis and lid oedema.
sparing of tendon
optic nerve
grossly thickened
>T--=-f"ii"""T-'-1 medial and inferior
rectus
Fig. 20.20 Symmetrical and inactive ('burnt-out') thyroid eye
disease. This patient has bilateral proptosis, and upper and lower
lid retraction. Upper eyelid retraction is attributed to excessive
sympathetic stimulation of Muller's muscles and fibrosis of the
levator complex.
Fig. 20.21 Asymmetrical orbital involvement is extremely
common. Dysthyroid eye disease is common in young women. The
cosmetic aspects of the disease cannot be overemphasized.
 CHRONIC AXIAL PROPTO

Fig. 20.22 Dysthyroid eye disease preferentially affects the inferior and medial recti, typically producing tethering of the globes in upgaze
and convergence. This patient shows limitation of all ocular movements except left downgaze. Elevation of both eyes is affected, left more
than right. She is convergent in primary gaze with a right over left hypertropia; abduction of both eyes is limited, the left more than the
right, from tethering by the medial recti.

Fig. 20.23 Corrective muscle surgery is contraindicated until the
diplopia has stabilized. Repeated monitoring of the ocular
movements with Hess charts or fields of BSV are very useful in
monitoring progress (see Ch. 18). Temporary Fresnel prisms give
symptomatic relief until the patient is ready for definitive surgery.
Fig. 20.24 This patient shows conjunctival and some corneal
exposure when gently closing her eyelids, as in sleep. With chronic
disease the lids often compensate to some extent but the patient
may have considerable problems with watering and discomfort of
the eyes from night time exposure.
 Al SYSTEM

Fig. 20.25 Acute proptosis and orbital congestion can lead to
corneal exposure and ulceration as well as optic neuropathy. High
dosage of intravenous steroids can help in the short term to reduce
proptosis but in severe cases urgent surgical orbital decompression
is required to save the eye.
Fig. 20.26 Enlarged muscle bellies cram the orbital apex and
cause optic nerve compression, especially in patients with minimal
proptosis; those with gross proptosis tend to 'decompress' their
own orbits. Decreasing acuity, colour loss, afferent pupillary defect
and a central scotoma suggest optic nerve compression. The optic
disc may be swollen, normal or atrophic. Many patients respond to
systemic steroids but orbital decompression is indicated if the optic
nerve compression is unrelieved. Intraorbital tension can be
assessed by gently ballotting the globes against the retrobulbar fat.

optic nerve

post surg ical decompression

medial recti prolapsing

into the ethmoid sinus

medial and lateral

wall removed

Fig. 20.27 Coronal scans show gross muscle hypertrophy crowding the orbital apex and causing optic nerve compression. Axial and
coronal scans show the postoperative appearances following decompression of both orbits into the ethmoidal and maxillary sinuses and
removal of the lateral wall relieving orbital apical congestion.
 CHRONIC AXIAL PROPTOSIS

ORBITAL VARICES

Congenital orbital venous malformations are a common cause of which raises the central venous pressure. Varices are usually
chronic axial proptosis. Patients usually present with a unilateral and typically present in young adults; visual loss is
characteristic history of variable proptosis with the eye uncommon. Accompanying venous malformations are sometimes
enophthalmic at rest but protruding on a Valsalva manoeuvre seen on the ipsilateral eyelids, face, nasal cavity or palate.

Fig. 20.28 Variable proptosis of the right eye is demonstrated in

this patient. On a Valsalva manoeuvre the right eye becomes
proptosed with ptosis of the upper lids due to increased pressure in
the malformation. Varices consist of ectatic vascular channels or a
segmentally dilated vein there can rarely thrombose or bleed
spontaneously causing acute painful proptosis.

,-- -----,---------, concave medial

orbital wall
varix of superior
ophthalmic vein
opaque posterior
dilated veins
ethmoidal sinus

Fig. 20.29 A CT scan shows varicosities of the superior

ophthalmic vein in this patient. Phleboliths may be seen as
calcification within the veins in some patients.

Fig. 20.30 Orbital vascular malformation structures can involve

adjacent structures. This patient shows associated venous
malformation of the palate.
'THE ORBIT AND LACRIMAL SYSTEM

CAROTICOCAVERNOUS FISTULAS

These arteriovenous communications between the carotid
arterial system and the cavernous sinus can occur spontaneously
or as a result of trauma; they may present either acutely or
chronically and be of either high-flow or low-flow type .
The clinical presentation depends on the rapidity of onset,
extent of vascular shunting and increased orbital venous pressure
and consequent orbital or ocular hypoxia. High-flow shunts
present with proptosis which may be bilateral and asymmetrical
due to communication with the contralateral cavernous sinus,
external ophthalmoplegia with orbital ischaemia from shunting,
and high venous pressure. Visual loss is caused by optic nerve or
intraocular ischaemia, rubeosis iridis may be seen and patients
may complain of a bruit. Low-flow shunts may present as a
glaucomatous eye with arterialized and engorged conjunctival
vessels (see Ch. 8).

Ophthalmic
artery
-------------------- --- ---- - ----------------
Cavern ous sinus 2 Fig. 20.31 High-flow fistulas result from traumatic tears of the
internal carotid artery in the cavernous sinus (1). Fistulas may
result from communication between the branches of the internal
carotid artery with the cavernous sinus; these are usually low flow
3 (2). Dural fistulas result from branches of the external carotid
Internal
carotid artery artery communicating with the cavernous sinus through dural
shunts. These are also low flow (3) . Fistulas frequently have
multiple communications. A combination of 2 and 3 is the
commonest. Low-flow fistulas may occasionally result from
Common
carotid artery
excessive straining (e.g. childbirth) and sometimes close
spontaneously.

Fig. 20.32 This patient suffered a severe head injury and fracture of the base of the skull in a motorcycle accident. His asymmetrical
proptosis was greater in the left eye and associated with a total ophthalmoplegia of the left eye and partial ophthalmoplegia of the right eye.
Pulsating exophthalmos and an audible bruit were present indicating a high-flow fistula. The conjunctiva of the left eye was chemotic and
its veins engorged. The eye was blind and there were signs of ocular hypoxia with a dilated, unreactive pupil. The right eye had normal
visual acuity. Intraocular pressure on the side of the fistula was higher with a larger pulse amplitude which can help in diagnosing cases
with low flow and mild signs.
 CHRONIC AXIAL PROPTOSIS

massive fistula

intern al carot id
post-embolization
artery
control of fistula

Fig. 20.33 CT shows proptosis and dilatation of the superior ophthalmic vein, a consistent finding in caroticocavernous fistulas. Carotid
angiography of the same patient demonstrates a massive fistula in the region of the cavernous sinus that was treated successfully by
embolization using a balloon catheter technique. The patient's chemosis, proptosis and ocular movements improved but the vision did not.

CAVERNOUS HAEMANGIOMA

Cavernous haemangiomas are the most common benign orbital commonly inferior and lateral to the optic nerve . Patients may
tumours of adults and often present as slowly progressive axial have visual symptoms from pressure on the optic nerve, disc or
proptosis. The mass is usually within the muscle cone, most macula.
 I HE URBII AND LACRIMAL SYSTEM

Fig. 20.34 CT shows a typical haemangioma as a well defined

mass that is distinct from the globe and optic nerve. Blood flow
through the lesion is sluggish and explains why lesions enhance
encapsulated
slowly and patchily following injection of contrast. The lesion was ~~-~-r--= haemangioma
removed intact through a lower-lid swinging flap.

Fig. 20.35 Pathology of the lesion shows large dilated vascular channels lined by endothelium with thick fibrous walls. The lesion is
encapsulated.

OPTIC NERVE GLIOMAS
Optic nerve gliomas are most commonly seen in children or
young adults; they present with unilateral proptosis and
diminished visual acuity (and should not be confused with the
rarer malignant glioblastoma seen in middle-aged men). About
60 per cent of affected children have cutaneous signs of
neurofibromatosis although the tumour is seen independently of
this disease. Most optic nerve gliomas behave as benign and
indolent hamartomas and do not appear to spread along the
optic nerve to invade the chiasm. However, intracranial invasion
is seen and it is extremely difficult to predict which lesions will
behave aggressively. MRI and computerized visual field analysis
Fig. 20.36 The neuroradiological appearances are characteristic. MRI shows an enlarged orbit with a smooth fusiform enlargement of
the optic nerve.
CHRONIC AXIAL PROPTOSIS E
are indispensable in demonstrating involvement of the
intracranial optic nerves and chiasm. Suddenly increased
proptosis and visual loss in some patients may result from
hydration of mucoid elements in the tumour rather than
aggressive or malignant change. The optic disc may be swollen or
atrophic. Indolent tumours are followed by observation. Radical
surgical excision of the optic nerve is reserved for progressive
enlargement of the tumour with a blind eye in the absence of
chiasma! involvement; extension into the chiasm may be treated
by palliative radiotherapy.
thickened optic
nerve extending
through f---++-Hf'---7:;;-..<F--'-.
optic canal
~\{:';;;J;~z:;:2"_J~~-J thickened
optic nerve
 AND LACRIMAL SYSTEM

Fig. 20.37 Tl-weighted MRI shows expansion of the intracranial

optic nerves and chiasm in a patient with neurofibromatosis who
had an extensive glioma involving the optic nerve, chiasm and
optic tracts.

lateral ventri cles

interna l
carotid ~.-~,..-,
pituitary
artery stalk

internal
carotid artery

expanded optic nerves

Fig. 20.38 The optic nerve is expanded as a smooth fusiform mass (left). Histological examination (right) shows proliferating spindle-
shaped pilocytic (hair-like) astrocytes forming intersecting bundles that distend the plial septa. Associated meningeal hyperplasia may be
seen over the lesion.
 CHRONIC AXIAL PROPTOSIS

MENINGIOMAS

Primary optic nerve meningiomas are rare tumours; they arise
from the arachnoid within the dura and infiltrate the
subarachnoid and subdural space to compress the nerve. The
characteristic presentation is of early and slowly progressive
visual loss with little proptosis; the optic disc is usually swollen or
atrophic. Patients tend to be middle-aged women. Optic nerve
meningiomas rarely occur in children in whom the course is more
aggressive and invasive and management more radical.
Occasionally, the subdural space surrounding the optic nerve
may be invaded by a middle cranial fossa meningioma extending
through the optic canal or superior orbital fissure; this is known
as a secondary optic nerve meningioma.

thickened optic nerves

calc ification

Fig. 20.39 CT characteristically shows tubular thickening of the optic nerve with areas of calcification with minimal proptosis. Bilateral
optic nerve involvement is well recognized, as in this patient; note that the left cavernous sinus is expanded by tumour. MRI with contrast
enhancement is necessary to determine the extent of intracranial involvement.

opticoci liary
shunt vessels

Fig. 20.40 Slow strangulation of the optic nerve produces chronic disc oedema followed by optic atrophy. Fundus photographs of the
same patient show opticociliary collateral vessels (shunting blood from the obstructed central retinal vein to the choroidal circulation) in
the right eye and optic atrophy in the left. Occasionally, aggressive meningiomas may even invade the optic disc.
 SYSTEM

Fig. 20.41 This pathological specimen shows a meningioma

surrounding the optic nerve. In adults the tumour is locally
invasive but slow growing. Limited surgical exploration may risk
spreading the tumour into the orbit and indolent tumours are best
either watched or completely excised; both types of treatment have
their protagonists. Radiotherapy may be considered for aggressive
recurrent tumours.
Left figure by courtesy of Dr M P Carey.

Fig. 20.42 Sphenoidal ridge meningiomas typically occur in middle-aged women. They are slow
growing over many years and produce painless proptosis from infiltration and thickening of the orbital
walls. This woman shows proptosis with the globe displaced inferiorly and swelling of the left temporal
fossa which is a characteristic feature of temporal bone involvement.

Fig. 20.43 The meningioma usually originates on the greater

wing of the sphenoid and infiltrates the bone producing thickening
and sclerosis (as shown on this CT). Optic nerve compression
occurs when the tumour affects the optic canal, and motility when
it spreads into the cavernous sinus. MRI is necessary to evaluate
intracranial spread fully. Surgical removal is unsatisfactory and
produces further visual loss or ocular motor nerve damage .
IDIOPATHIC ORBITAL INFLAMMATORY DISEASE AND ORBITAL APEX SYNDROME

Formerly called ' pseudo-tumours' these nonspecific, non-
neoplastic inflammatory lesions arise in the orbit with diverse
pathological appearances but generally display a polymorphous
chronic inflammatory cell infiltration. Inflammation associated
with known predisposing factors such as dysthyroid eye disease,
sarcoid, chronic infection, foreign body reactions or secondary to
a vasculitis (such as Wegener's granuloma or polyarteritis nodosa)
should not be included. Except for myoslt!s and orbital apex
inflammation (where there is a characteristic history, clinical
signs and imaging) almost all such lesions should be biopsied
before starting therapy. Differentiating pathologically between
idiopathic orbital inflammatory disease (IOID), lymphoid
hyperplasia and lymphoma can be difficult but recent advances
with immunological cell markers and genomic analysis help.

Sites of IOID

Fig. 20.44 IOID is uncommon and may occur anywhere in the

Orbital
orbit such as in the lacrimal gland, intraconal space, external
ocular muscles or orbital apex. Presentation is usually acute or
subacute and pain is an important feature; depending on the
location there may be acute proptosis, chemosis, motility
disturbance or visual deterioration. A few present as chronic,
painless space-occupying lesions. The orbital apex is a common site
for IOID and produces a characteristic syndrome of painful
proptosis and visual loss with third, fourth, fifth and sixth nerve
palsies (the 'orbital apex syndrome'). Lesions found slightly more
si nus
posteriorly in the cavernous sinus produce the same signs but
without visual loss.

Fig. 20.45 This middle-aged man presented with painful proptosis and complete ptosis coming on over a few days. There was complete
left ophthalmoplegia from third, fourth and sixth nerve palsies. The close-up photograph (b) shows the ocular motor paresis with the
patient attempting to look right. Note the conjunctival injection. Sparing of the pupil with the third nerve palsy is due to a concomitant
Horner's syndrome. Visual acuity was reduced to 201100. Colour perception was decreased in the left eye and there was a left relative
afferent pupillary defect with a relative central scotoma in the visual field. The optic disc appeared normal.
 ACRIMAL SYSTEM

abnormal cavernous sinus

Fig. 20.46 CT shows proptosis with an orbital apex mass

extending forwards into the lateral rectus and posteriorly through
the superior orbital fissure into the cavernous sinus. MRI would be
necessary to discern the degree of cavernous sinus involvement.

proptosis

involvement of LR tendon

swollen lateral rectus

Fig. 20.47 This 37-year-old radiologist presented with horizontal

diplopia worse on left gaze with pain and proptosis. The scan
shows a thickened lateral rectus with involvement of the tendon
characteristic of myositis. The adjacent orbital fat is involved with
mild proptosis. The patient was treated with steroids; failure to
make a full and rapid clinical recovery requires biopsy to exclude
other pathology.

Fig. 20.48 A range of pathology may be seen in I OlD. Germinal follicle formation (left) is a feature of reactive lymphoid hyperplasia, a
benign lesion that will respond satisfactorily to steroid therapy or even resolve. Lymphomas (right) also show a lymphoid infillrate. Many
lesions are difficult to classify without immunohistological techniques which are necessary for accurate diagnosis. Monoclonal
immunoglobulin expression is indicative of malignancy, but 15-20 per cent of patients with polyclonal tumours eventually develop
lymphoma.
 CHRONIC NONAXIAL PROPTOSIS I
CHRONIC NONAXIAL PROPTOSIS

Nonaxial proptosis, easily identified using a perspex ruler, is lesion. This localizes the lesion and often gives an indication of its
caused by an asymmetrical lesion placed external to the ocular likely nature.
muscle cone; the globe tends to be displaced away from such a

DERMOID CYST

Dermoid cysts are common lesions usually presenting in children superior part of the orbit, medially or laterally. They grow slowly
and young adults. They are formed by epidermal inclusions from and are usually painless.
malclosure of the embryonic facial clefts and tend to lie in the

Fig. 20.49 A dermoid cyst in the superior part of the orbit displaces the right globe inferiorly. The patient was referred as having a right
'ptosis' without diplopia. The other child has a more superficial dermoid cyst presenting as a lump in the upper lid.

Fig. 20.50 Slow expansion of the cyst produces a bony skull defect with a sharp sclerotic margin readily seen on CT. Dermoid cysts must
be evaluated and excised with care as they may occasionally penetrate through to the dura to require a combined neurosurgical excision.
Partial excision must be avoided as the remnants produce chronic inflammation with a discharging sinus.
 I HE ORB I I AND LACRIMAL SYSTEM

Fig. 20.51 The oily sebaceous contents of a dermoid cyst can

leak and cause a lipogranulomatous reaction and acute cellulitis. In lateral orbital rim
this patient inflammation improved after 2 weeks of nonsteroidal malleable retractor
anti-inflammatory drug therapy. At operation the dermoid is
dumb-bell shaped, communicating through a hole in the bone.

NEUROFIBROMATOSIS (VON RECKLINGHAUSEN'S DISEASE)

Neurofibromatosis (NF) is two separate diseases. NF1 is the
commoner type with the well recognized cutaneous stigmata of
cafe-au-lait spots, neurofibromas and Lisch nodules on the iris
(see Chs 2 and 9). The gene is located on chromosome 17, has
an incidence of 1 in 3000 live births and a dominant inheritance
with high penetrance but variable expressivity; new mutations are
common. There is a wide variation in the disease spectrum
between patients and within families. The gene for NF2 is located
on chromosome 22 and is much rarer with an incidence of 1 in
40,000. It is dominantly inherited and is characterized by
bilateral acoustic neuromas (see Ch. 17). Cafe-au-lait spots and
neuro-fibromas are less prominent than in NF1. Lisch nodules
can occur in both conditions. Patients with NFl tend to develop
neural or astrocytic tumours such as astrocytomas or gliomas,
whereas those with NF2 develop tumours of nerve sheaths and
coverings such as schwannomas and meningiomas.

Fig. 20.52 Neurofibromatosis is sometimes associated with

orbital bony malformations, particularly absence of the greater and absent posterior
lesser wings of the sphenoid. In this case the intracranial contents absent orbital orbital wall
roof, frontal with temporal
of the middle fossa (temporal lobe) lie directly in contact with the
lobe prolapsing H-'t-r---...~ lobe prolapsing
orbit and produce a characteristic pulsating proptosis from the into orbit
into orbit
transmitted cerebral pulse wave. and sinuses

Fig. 20.53 CT demonstrates a large bony orbital defect in the

sphenoid on the right.
 CHRONIC NONAXIAL PROPTOSIS

LACRIMAL FOSSA LESIONS

Careful differential diagnosis of lesions located in the lateral part of the orbit is especially important owing to their radically different
methods of management.

Lacrimal gland/fossa mass

I I
I
Duration of
l 1
Long (> 1 year)
symptoms I I Short(< 1 yea r)
I
I I
l l l 1

T ~
Imaging Normal or Normal
pressure I I
changes I
l 1
With Without

I
Destructive
changes
I l Pressure
chan ges
I I
Destructive
changes
I
inflammatory
sign s
inflammatory
signs

l
4 weeks anti-inflammatory

I treatment
I
l l
I uc; mpm"d I~

Mass not Mass

reg ressing regressing

l
Watch,
probably
inflammatory,
infective etc

En bloc
Surgical lncisional lncisional lncisional lncisional
excisional
technique
I biopsy
I biopsy I biopsy
I I biopsy
I biopsy

I
J. J.
Benign mixed
Likely Carcinoma, inflammatory,
Carcinoma cell tumour Carcinoma
diagnosis I I (dermoid cyst) I I I IOID etc
I

Fig. 20.54 Flow diagram of the differential diagnosis of lacrimal fossa masses based on the duration of symptoms and findings on
imaging helps to provide a clinical diagnosis. Pleomorphic adenomas (benign mixed tumours) occur in adults aged 20-60 years and are
characterized by a slow, painless, progressively enlarging, lacrimal fossa lesion that has usually been present for at least a year before
presentation. A mass can be palpated and CT may show diffuse enlargement of the lacrimal fossa without bony invasion. These lesions
must be excised en bloc by lateral orbitotomy as biopsy or partial excision leads to local recurrence with invasion of the surrounding
structures and a potentially fatal outcome. Carcinomas characteristically have a short progressive history of less than 1 year and are painful;
CT may show bony invasion or calcification within the tumour. Diagnosis is made by biopsy with the option of debulking and
radiotherapy. Patients with lacrimal gland carcinomas tend to have a poor prognosis. Other causes of lacrimal fossa masses are viral adenitis
(e.g. mumps), inflammatory granulomas (sarcoid), IOID or dermoids.
Fig. 20.55 This elderly patient had a painless long-standing mass in the lacrimal fossa with the globe displaced medially and downward,
as is typical of a pleomorphic adenoma . A close-up photograph demonstrates the swelling more clearly (b).

lacrimal gland mass

pressure indentation of
lateral orbital wall

Fig. 20.56 CT showed an enlarged lacrimal fossa and solid mass

typical of a pleomorphic adenoma (which is to be distinguished
from a dermoid cyst that looks cystic) with a sharp sclerotic bony
margin.

Fig. 20.57 The histological appearance of a typical pleomorphic adenoma varies considerably within itself. Epithelial and myoepithelial
cells proliferate and glandular and myxoid tissues are seen. Irregular epithelial lined tubules contain mucus and keratin; the myxoid stroma
may contain fat and cartilage. There is a pseudocapsule which is often penetrated by nodules of tumour tissue that lead to local recurrence
unless excision is complete.
 CHRONIC NONAXIAL PROPTOSIS

Fig. 20.58 In contrast to a benign mixed tumour, this girl has an

adenoid cystic carcinoma that presented with pain in the right
lacrimal fossa area and a palpable mass which had been present for
a few months.

infiltration of lateral
--r.;..-..~'m-1 orbital wall with
bone destruction

intracranial extrusion
through superior
orbital fissure

Fig. 20.59 CT showing an adenoid cystic carcinoma extending posteriorly along the lateral orbital wall to the superior orbital fissure,
with bony erosion and invasion of the temporal fossa through the superior orbital fissure. The patient died a year later, despite radiotherapy.

tumour infiltration
~~~~~~ of bone

'--::=:::::::::::::~==::::::::-==~-;---1 bone

Fig. 20.60 Histological examination of an adenoid cystic

carcinoma shows solid and cystic areas. In this specimen the
tumour is infiltrating bone. The characteristic pain of lacrimal
carcinoma is produced by neural invasion.
 I HE URBII AI'JD LACRIIVIAL 5 t 5 I EIVI

MEDIAL WALL ORBITAL LESIONS

The globe is displaced laterally by an external mass in the medial rhabdomyosarcomas in children. Wegener's granulomatosis is an
wall of the orbit. The most common lesions are mucoceles and important cause of an inflammatory lesion at this site resulting
carcinomas of the ethmoidal sinuses in adults or from contiguous spread from the nose.

medial rectu s

defect in sinus roof

Fig. 20.61 An ethmoidal mucocele causes globe displacement. The absence of orbital inflammation is demonstrated by the normal dark
signal of the orbital fat; compare this to the 'dirty' fat signal ofiOID (see Fig 20.47).

Fig. 20.62 These two patients have carcinomas of the ethmoidal sinus. The globe is displaced laterally in the younger man (left), whereas
the base of the nose is expanded in the older man (right). Because symptoms are initially nonspecific (nasal discharge, bleeding, etc.),
patients with paranasal sinus carcinomas tend to present late and consequently have a poor prognosis.
r-- --.--- - - - -- - -- - - - - - - - - - - - - - - - - - - - - -
ORBITAL TRAUMA
A blunt injury to the globe can increase intraorbital pressure to
produce a 'blow-out' fracture into the maxillary or ethmoidal
sinuses (see Ch. 18) .
The optic nerve may be compressed or injured in the tight
confines of the orbital apex. This may occur from a fractured
optic canal or penetrating orbital trauma. It may also result from
- -- ---- ---~-----------------------------
ORBITAL TRAUMA
opaque ethmoidal
sinuses
Fig. 20.63 CT scans show an ethmoidal carcinoma infiltrating
the sinus and destroying the medial orbital wall.
a haematoma-usually a subperiosteal or intraorbital haematoma
following fracture (or orbital or cosmetic surgery)- that
compresses the optic nerve and produces rapidly progressive
visual loss. In this situation, prompt orbital drainage may
sometimes prevent loss of sight.
Fig. 20.64 This patient presented with no perception of light in
the right eye following a gardening accident in which she poked the
end a fine cane support into the right eye as she bent over. Closer
examination showed a conjunctival laceration over the medial
aspect of the globe. The tip of the cane displaced the globe laterally
and travelled medially along the orbital wall to transect the optic
nerve at the orbital apex. The right pupil has been dilated for
diagnostic purposes.
 ORBIT AND LACRIMAl SYSTEM

Fig. 20.65 CT and skull radiography show a shotgun pellet lodged in the left orbital apex following a sporting accident. The patient had
an inferior altitudinal field loss in the affected eye that remained unchanged on subsequent examinations. Surgical removal of the pellet is
contraindicated as this is likely to cause further visual loss.

opaque
ethmoidal sinuses hH:+<=:=~;&ll
fracture through
orbital apex
fracture

Fig. 20.66 This patient suffered multiple fractures after a fall when stealing the lead from a church roof. On resuscitation he was found
to be blind in his right eye and CT showed a fracture through the optic canal.

ENOPHTHALMOS
Enophthalmos is a subtle sign that may be overlooked. Reduced
orbital soft tissues (small globe or fat atrophy), increased bony
orbital dimensions (e.g. blow-out fracture) or cicatricial orbital
disease are causes. Enophthalmos is associated with metastatic
THE LACRIMAL DRAINAGE SYSTEM
Accessory lacrimal glands in the conjunctiva produce the basal
tear secretion; reflex lacrimation comes from the lacrimal gland.
The basal secretion rate is about 1 j..ll/min and most of this is lost
by evaporation. Basal secretion declines with age so that elderly
patients may be asymptomatic despite tear drainage being
completely obstructed.
Entry of tears into the drainage system is complex. The
puncta lie in the meniscus of the tear film with tears entering the
puncta by capillary attraction after being swept medially when
the lids blink. The pretarsal and preseptal orbicularis muscles
contract to shorten the canaliculi and dilate the fundus of the
lacrimal sac pumping tears into the system. Gravity aids their
THE LACRIMAL DRAINAGE SYSTEM
tumours (especially scirrhous carcinoma of the breast), IOID and
following irradiation due to soft tissue volume loss and
cicatrization.
Fig. 20.67 This woman has enophthalmos from a sclerosing
metastatic breast carcinoma with ptosis and limited ocular
movement.
drainage through the nasolacrimal duct. More tears enter the
lower canaliculus than the upper but drainage through the upper
canaliculus is often sufficient to prevent symptomatic epiphora if
the lower is blocked. Overflow of tears (epiphora) is due to lid
malposition or an imbalance between production, evaporation
and outflow. Hypersecretion of tears may be secondary to
irritation of the ocular surface (e.g. trichiasis, entropion) or reflex
lacrimation secondary to conjunctival or ocular surface disease.
Outflow obstruction may be at the level of the punctum,
canaliculi, nasolacrimal sac or nasolacrimal duct. Accurate
evaluation of the cause of epiphora is essential to implementing
appropriate treatment. (Dry eyes are discussed in Ch. 5.)
2 THE ORBIT AND LACRIMAL SYSTEM

Main Superior Nerve of Fig. 20.68 Innervation of the lacrimal gland.

sensory sa livary Vllth Trigeminal pterygoid cana l Lac ri ma l Frontal Lacrimal Parasympathetic fibres arise in the lacrimal
nucleus of V nucleu s nerve ganglion (Vidian nerve) nerve nerve gland nucleus, which is part of the superior
salivatory nucleus just caudal to the seventh
nerve nucleus in the floor of the fourth
ventricle. Leaving the brain in the nervus
intermedius they pass without synapse through
the geniculate ganglion to the greater
superficial petrosal nerve, running forwards in
a groove on the floor of the petrous temporal
bone. At the foramen lacerum they are joined
by sympathetic fibres of the deep petrosal
nerve from the carotid plexus to form the
nerve of the pterygoid canal (vidian nerve) .
The lacrimal secretory fibres synapse in the
sphenopalatine ganglion and join the
zygomaticotemporal branch of the maxillary
nerve. This nerve passes through a foramen in
the lateral orbital wall to join the lacrimal
branch of the ophthalmic division ofV in the
orbit to supply the lacrimal gland. Crocodile
tears are due to aberrant innervation of the
lacrimal gland by misdirected secretomotor
fibres from the superior salivary nucleus
producing epiphora in response to stimulation
of taste. It can occur congenitally or with
acquired lesions of the facial nerve proximal to
Tympanic Chorda Internal Deep petrosal Li ngual Subma n- Sa livary the geniculate ganglion.
membrane tympani carotid nerve nerve dibular glands Adopted from Bran et al. Wolff's Anatomy of the
plexus (sympathetic f ibres) gang li on
Eye and Orbit. ©1997 London: Hodder Arnold
Publishers.

upper pu nctum
and cana liculus
medial canthal tendon
covering lacrimal sac

inferior tubinate
nasolacrimal duct

intraorbita l nerve

Fig. 20.69 A cadaver dissection shows the medial palpebral ligament lying anteriorly to the canaliculi. The orbicularis has been excised to
show the lacrimal sac and the nasolacrimal duct passing downwards through the maxilla to enter the nasal cavity under the inferior
turbinate . Mucosal flaps within the nasolacrimal duct act as valves and prevent retrograde air entry into the lacrimal sac.
By courtesy Dr Ted Garway Heath.
 TESTS OF OUTFLOW PATENCY

Deep insertions of orbiculari s

r --1-- - - - - - - - - into lacrimal sac and posterior
lacrimal crest
Superficial insertions of pretarsal Fig. 20.70 A diagram shows the
1---- - - ----7""--- and preseptal orbicularis anatomy in more detail. The upper
into medial palpebral ligament
and lower puncta enter the
canaliculus as a short vertical
passage that turns medially in the
lid margin. The canaliculi have a
length of about 8 mm. They
anastomose to form the common
canaliculus which opens by a single
orifice into the lateral wall of the
Anterior lacrimal crest
lacrimal sac. Palpebral fibres from
the orbicularis oculi muscle are
Nasolacrimal duct --+--+~
inserted superficially into the medial
palpebral ligament and deeply into
the lacrimal fascia surrounding the
--+- -- - Inferior turbinate
fundus of the sac. The nasolacrimal
M axillary duct has an intraosseus length of
antrum approximately 12 mm and opens
into the inferior meatus of the nose.

TESTS OF OUTFLOW PATENCY

The patency of the outflow system can be shown by the Jones'
dye tests, syringing, dacryocystography (DCG) or lacrimal
scintillography. Although syringing is commonly used to
diagnose patency it does not represent normal physiology as
saline is forced under high pressure through the system. The
Jones' test and lacrimal scintillography are conducted under near
physiological conditions. DCG demonstrates the anatomy and is
useful in investigating canalicular problems, craniofacial
anomalies, facial trauma and surgical failures .

Fig. 20.71 The Jones' dye test is a refinement of syringing the nasolacrimal system. Its main use is in the evaluation of unrelieved
symptoms following dacryocystorhinostomy (DCR). Fluorescein drops are instilled into the conjunctival sac. A cottonwool bud, soaked in
local anaesthetic, is placed in the inferior meatus or alongside the rhinostomy site after DCR and examined for signs of fluorescence after 5
min. Identification of nasal dye indicates a physiologically patent, although not necessarily normally functioning, system. Many normal
patients have a negative test at this stage and, if so, excess fluorescein is washed from the conjunctiva and the canaliculi are syringed with
clear saline. Entry of fluorescein into the nose indicates that dye has entered the sac; if clear saline is seen, fluorescein has not entered the
sac and indicates puncta! or canalicular stenosis. The absence of saline entering the nose indicates a complete obstruction.
THE ORBIT AND LACRIMAL SYSTEM

technical
overspi ll of
dye along lid
margin
mucocele

Fig. 20.72 DCG requires the injection of a radio-opaque

contrast medium (generally oil based) into the lacrimal drainage
system. In this patient contrast passed normally through the left
side but on the right it outlined a lacrimal sac mucocele.

OUTFLOW OBSTRUCTION

CONGENITAl BlOCKAGE OF THE NASOlACRIMAl DUCT

The nasolacrimal duct is formed by a cord of ectoderm that at the third month of gestation. The central cells of the cord
becomes embedded in mesoderm in the cleft between the degenerate to leave a lumen and this process extends upwards
maxillary and lateral nasal processes. This cord grows upwards and downwards to reach the nasal cavity.
and bifurcates to form the canaliculi which reach the lid margins

Fig. 20.73 At birth the process is usually complete but a

membrane may persist at the lower end and fail to perforate
leaving the child with a watering eye. This can be ruptured with a
probe under general anaesthesia if it has not perforated
spontaneously by 1 year of age .
 fi stula opening below
medial canthal t en don

Fig. 20.74 This child has a congenital lacrimal fistula with an

aberrant punctum lying over the lacrimal sac.

Fig. 20.75 Puncta! stenosis follows conjunctival scarring from such inflammatory causes as trachoma, chronic staphylococcal lid disease,
Stevens-Johnson syndrome, ocular pemphigoid and topical drugs. Provided the canaliculus is not involved, dilating and opening the
punctum with a 'two or three snip' operation cures the condition.

su lph ur granules from

incised low er canaliculu s t--\-'=-==::'_,;.,~"1
upper canalicu lus of another patient

Fig. 20.76 Canaliculitis occurs most commonly from Actinomyces israelii infection. The infected canaliculus becomes chronically red,
swollen and tender. Pressure over the swelling sometimes reveals stringy, tenacious mucous and 'sulphur granules' at the punctum.
Treatment is by incision and curettage of the canaliculus and a short course of topical penicillin.
I HE OKbll AND LACRIMAL SVS I EM

Fig. 20.77 Typical clusters of Gram-positive Actinomyces can be

seen in the 'sulphur granule' curettings of this patient.

Fig. 20.78 Obstruction of the nasolacrimal duct as a result of

chronic infection or irritation may lead to stasis and an acute
infection of the lacrimal sac. Patients present with epiphora and an
acutely painful, swollen mass over the area of the lacrimal sac; this
may form an abscess and require incision, drainage and systemic
antibiotics. Incision, when required, should be performed as far
laterally as possible, to facilitate subsequent DCR. DCR is usually
necessary to reconstitute lacrimal drainage as soon as the acute
inflammation has subsided.

Fig. 20.79 Chronic obstruction of the nasolacrimal duct can lead

to a watering eye and a mucocele of the lacrimal sac. Provided the
canaliculi are patent, pressure over the sac causes mucoid material
to regurgitate through the puncta.

Fig. 20.80 A painless, irreducible mass that extends above the

medial canthal tendon may signify a lacrimal sac tumour. There
may be associated blood-stained tears or bloody reflux with
syringing. Ultrasound will show whether the lesion is solid or cystic
and further evaluation with CT or MRI is necessary to plan
surgery.