PART II

Via Paccagnella 11
30174 Zelarino-VENEZIA
(ITALY)

CORNEAL DYSTROPHIES &

DEGENERATIONS
Dystrophy
( From Greek: )
Bad Development, Structural
Decay Induced by an INTERNAL
( GENETIC ) Factor

CORNEAL DYSTROPHIES &

DEGENERATIONS
Degeneration
( From Latin: Degenerare )

Derailment, Structural Change

Induced by EXTERNAL Factor

DYSTROPHY

DEGENERATION

CORNEAL DYSTROPHIES &

DEGENERATIONS
BULLOUS KERATOPATHY
Degeneration
(s/p Cat. Op.)

Dystrophy
(Fuchs)

CORNEAL DYSTROPHIES &

DEGENERATIONS
PELLUCID MARGINAL
DEGENERATION

Degeneration

Dystrophy

CORNEAL DYSTROPHIES &

DEGENERATIONS
DEGENERATION

DYSTROPHY

UNILATERAL

BILATERAL

CORNEAL DYSTROPHIES &

DEGENERATIONS
DEGENERATION

DYSTROPHY

ASYMMETRIC

SYMMETRIC

CORNEAL DYSTROPHIES &

DEGENERATIONS
DEGENERATION

DYSTROPHY

POSTOPERATIVE

SPONTANEOUS

CORNEAL DYSTROPHIES &

DEGENERATIONS
DEGENERATION

DYSTROPHY

PERIPHERAL

CENTRAL

(usually)

(usually)

CORNEAL DYSTROPHIES &

DEGENERATIONS
DEGENERATION

DYSTROPHY

VASCULARIZED

AVASCULAR

CORNEAL DYSTROPHIES &

DEGENERATIONS
DEGENERATION

DYSTROPHY

LATE ONSET

EARLY ONSET

CORNEAL DYSTROPHIES &

DEGENERATIONS
DEGENERATION

QUICK
PROGRESSION

DYSTROPHY

SLOW
PROGRESSION

CORNEAL DYSTROPHIES &

DEGENERATIONS
DEGENERATION

DYSTROPHY

SECONDARY

PRIMARY

CORNEAL DYSTROPHIES &

DEGENERATIONS
DEGENERATION

DYSTROPHY

NON HEREDITARY

HEREDITARY

(Autosom. Dom.)

CORNEAL DYSTROPHIES
CLASSIC MORPHOLOGIC
(ANATOMIC) CLASSIFICATION
Epithelium (e.g. map-dot-fingerprint)
Bowmans Layer (e.g. Reis-Bckler)
Stroma - Deposition (e.g. Graenouw)
Stroma - Ectasia (e.g. Keratoconus)
Endothelium (e.g. guttata, Fuchs)

Epithelial Basement Membrane

Dystrophy
The most common dystrophy seen in
clinical practice
AD but with incomplete penetrance; usually
sporadic
bilateral, more common in women
Onset in the 2nd decade
10% develop recurrent epithelial erosions

Epithelial Basement Membrane

.
Dystrophy
Most patients with
epithelial basement
membrane dystrophy
have only the map
changes which
represent basement
membrane within the
Map
changes in
epithelium

epithelial
basement
membrane
dystrophy.

Epithelial Basement Membrane

Dystrophy
Both microcystic changes of
Cogan and
maplike changes together.
Usually, the microcysts are in
the area of basement
membrane and not in the
clear lacuna as noted here.

Epithelial Basement Membrane

Dystrophy
Map-dotfingerprint,
Cogans
microcystic
dystrophy
The intraepithelial
microcysts in the
slit just at the
inferior margin of
the visual axis.

Epithelial Basement Membrane

Dystrophy

Parallel lines and

fingerprint lines

Retroillumination of
highlighted basement
membrane dystrophy seen
as fingerprint lines and map
patterns.

Epithelial Basement Membrane

Dystrophy
Bleb pattern is
seen in
retroillumination
against the fundus
red reflex.
The bleblike
deposits beneath
the basal
epithelium are seen

Epithelial Basement Membrane

Dystrophy
Fluorescein stains
The lack of epithelial
integrity (1),
which leads to
continued symptoms
from recurrent
corneal erosion.
Epithelial basement membrane
dystrophy and recurrent corneal
erosion in the lower third of the cornea.

Abnormal multilaminar basement membrane (BM)

in normal location (1)
intraepithelially (2)
BM thickens and blocks normal migration of epithelial cells toward
the surface.Trapped epithelial cells degenerate to form:
intraepithelial microcysts (3)
that slowly migrate to the surface (4)
Abnormal basement membrane produces map and fingerprint
changes, microcysts produce the dot pattern seen clinically

Epithelial Basement Membrane

Dystrophy

intraepithelial microcyst
(Cogan)

Debridement specimen of epithelium

Epithelial Basement Membrane

Dystrophy
MANAGEMENT:
Natural tears
Epithelial debridement
Patching
BCL
Phototherapeutic keratectomy
20G Needling to anchor the epithelium

Meesmann Dystrophy

Retroillumination

Very rare- bilateral

-epithelial dystrophy
AD with gene locus on
12q13 or 17q12
Epithelial microcysts
consisting of epithelial
cell debris concentrated
centrally

Management: Lubrication, BCL, or

PTK

Meesmann Dystrophy

Microvacuoles in
retroillumination.
These are fine vacuola
changes in the
epithelium
Intraepithelial cysts
Thickening of
epithelial basement
membrane

Meesmann Dystrophy

NORMAL ENDOTHELIUM !!!

Lisch Corneal Dystrophy

X-linked on Xp22.3
Gray bands of densely
crowded clear microcysts
in a whorl configuration
Symptoms:
VA, No pain
Treatment:
Debridement (if

Reis-Bckler Dystrophy
AD, chromosome 5q31 (same
as granular,
lattice, and Avellino)
Onset in second decade
Recurrent erosions, decreased
VA (anterior scarring)
Gray-white, fine, round
central opacities in
Bowmans layer,

Reis-Bckler Dystrophy
Progresses with age
Laying down of irregular
bands of collagen
replacing Bowmans
layer
Sawtooth fashion,
corresponding to
subepithelial opacities

Reis-Bckler Dystrophy
Rodlike
granules, seen
by transmission
electron
microscopy in
the superficial
stroma and in
the region of
Bowmans layer,

Reis-Bckler Dystrophy
TREATMENT:
Superficial keratectomy ?
Lamellar keratoplasty ?
PTK ???
Rarely PK
Recurrence in the graft (interface for LK) is very
common

Reis-Bckler Dystrophy
Recurrence 2
years after
excimer laser
ablation (area
of treatment !!!)

Thiel-Behnke Dystrophy

AD, Chromosome 10q24

Similar to Reis-Bckler, honeycomb pattern,
curly fibers
Treatment: same

Thiel-Behnke Dystrophy
Curly filaments
(TEM) in the
region of
Bowmans
layer

Thiel-Behnke Dystrophy
Several years after
corneal
transplantation there
is recurrence of the
pathology in the
region of Bowmans
layer and superficial
cornea.

Ring like or honeycomb appearance

Thiel-Behnke Dystrophy
Thiel-Behnke
Dystrophy
pre-SALK
Thiel-Behnke
Dystrophy
post-SALK

Lattice Dystrophy
(Haab-Dimmer)
AD, chromosome 5q31:
Linear amyloid deposits
concentrated in anterior
stroma and subepithelial
areas
Stains orange-red with
Congo Red dye

Lattice Dystrophy
(Haab-Dimmer)
Refractile lines, or lattice
lines, best seen on
retroillumination
Central and subepithelial
white dots
Diffuse anterior stromal
haze
Clear cornea inbetween lines

Lattice Dystrophy
(Haab-Dimmer)
Classic lattice dystrophy
Chromosome 5q31
Onset at end of first decade
with recurrent erosions
preceding stromal changes
Treatment: PK or DALK
usually needed by sixth
decade

Lattice Dystrophy
(Haab-Dimmer)

Branching, doubly relucent lines

Glassy dots in ant. stroma

Fine lattice lines seen on
retroillumination
Prominent lattice lines and
stromal haze
Congo red staining
Green birefringence with
polarized light
Diffusely involved cornea

Lattice Dystrophy
(Meretoja Syndrome)
Associated with systemic

amyloidosis
Chromosome 9q34
Onset third decade with
recurrent erosions
More delicate, sparse,
radially oriented
lattice lines

Lattice Dystrophy
(Meretoja Syndrome)

Systemic features:
progressive B cranial and
peripheral neuropathy
dysarthia
dry and lax itchy skin, mask
like facies
protruding lips
pendulous ears

Granular Dystrophy
AD, chromosome 5q31
Corneal stroma clear
inbetween opacities

Hyaline deposits that stain

red with Masson
trichrome stain

Granular Dystrophy
See sharply demarcated
deposits resemblingcrumbs
or snowflakes in the central
anterior stroma, often
distributed in a radial
fashion
In time, number, size, and
depth of deposits increases
with gradual confluence and
diffuse opacity

Granular Dystrophy
Treatment: PK or DALK by age
40-50
Recurrences frequent
DO NOT treat
with excimer laser !!!
Histology shows amorphous
hyaline deposits that stain red
with Masson trichome

Granular Dystrophy
(Type II Avellino)
Combination of
patterns (bread
crumbs more
superficial, snow
flakes deeper)

MK-ASSISTED ANTERIOR LK

SALK Compares to LASIK

+/- Sutures
1-Month Healing
Minimal Postop
Refr. Error

COMPLICATIONS
Dystrophy Recurrence
4/23 (17%)

Pre-SALK

Post-SALK

4-years
Post-SALK

DYSTROPHY RECURRENCE
Superficial
Recipient
Stroma
!!!
(Intracorneal)

DYSTROPHY RECURRENCE

After PTK and PK Recurrence

is SUBEPITHELIAL!!!

HISTOLOGY OF RECURRENCE

PAS

Trichrome Masson

Macular Dystrophy

Least common among stromal

dystrophies
AR, Chromosome 16q22
Involves the whole cornea,
(stroma opaque inbetween
opacities) including
endothelium
Pathogenesis: GAGs that
accumulate in the endoplasmi
reticulum, stain with colloidal
iron and Alcian blue

Macular Dystrophy

Deep
Periferal
Lesions

Type I
more prevalent
normal synthesis of dermatan sulfateproteoglycan
Erroneous synthesis of keratan sulfate
Type II
normal ratio of keratan sulfate and
dermatan sulfate but
decresed overall synthesis
Tratment: Treat recurrent erosions,
PK
Recurrence relatively rare

Schnyder crystalline corneal

Dystrophy

Central crystal deposition

only in 50% of cases

Rare, slowly progressive

AD, chromosome 1p36
Onset as early as first year
of life, but diagnosis
usually not made until
second or third decade
Disorder of corneal lipid
metabolism
Associated with increased
cholesterol in 50% of
patients.

Schnyder crystalline corneal

Dystrophy

Central Cristalline
Deposit

Central oval subepithelial

opacities (cholesterol)
Central corneal
opacification, arcus
Decreased corneal sensation
Management: Check lipid
panel, PK
Recurrence can occur

Fuchs Dystrophy
Very common
May be AD but genetics
not cleared yet
Female preponderance
Onset after age 50
Ranges from
asymptomatic guttata to
a decompensated cornea
(Bullae)

Fuchs Dystrophy

Corneal guttae
with melanin
granule
pigmentation

Pathogenesis: reduction
in Na, K-ATPase pump
sites and/or function
Increased corneal edema
and deposition of
collagen and
extracellular matrix in
Descemets membrane

Fuchs Dystrophy
Stage 1: gradual increase in
cornea guttata with
peripheral spread - beaten
metal
Stage 2: endothelial
decompensation leading to
stromal edema and blurred
vision, initially worse when
waking up

Fuchs Dystrophy

Stage 3: Persistent
epithelial edema
leading to microcysts
and bullae which
cause pain upon
rupture

Fuchs Dystrophy
Check pachymetry and specular
microscopy (peripheral cell count !!!)
TREATMENT:
Reduce edema with NaCl drops
Lower IOP ??? (ridiculous !!!)
BCL to enhance evaporation
In the past PK- NOW DSAEK

Posterior Polymorphous
Dystrophy (PPD)

Uncommon, slowly
progressive
AD (AR), Chromosome 20q11
Onset birth or soon thereafter
Areas with endothelial cells
that behave like epithelial
cells (microvilli)

Posterior Polymorphous
Dystrophy (PPD)

These cells
show microvilli
stain positive for keratin
rapidly grow
have intracellular
desmosomes
Descemets membrane is
thickened
Diffuse
Opacities

Linear Band
Lesion

DSAEK in PPD

PPD (Age=12)
BSCVA = 1/10
Ref. = +2.00 sph.

1 y. post-DSAEK
BSCVA = 10/10
Ref. = +1.00 sph.
-0.75 cyl. @ 170

Congenital Hereditary Endothelial

Dystrophy (CHED)
Autosomal Recessive

(Dominant)
Early Onset
Bilateral Clouding
Amblyogenic
NORMAL ANATOMY !!!

DSAEK in CHED

Age = 9 years BSCVA

= 2/10
Ref. = +2.00 sph.
-1.00 cyl. @ 65

3 y post-DSAEK
BSCVA = 8/10
Ref. = +2.25 sph.
-2.25 cyl. @ 150

CORNEAL DYSTROPHIES &

DEGENERATIONS
BAND KERATOPATHY

EDTA ABRASION
(with normal endothelium!)

CORNEAL DYSTROPHIES &

DEGENERATIONS
SALZMANN

MAP-DOT-FINGERPRINT

EPITHELIAL DEBRIDEMENT
(PTK)

CORNEAL DYSTROPHIES &

DEGENERATIONS
SUPERFICIAL STROMAL DYSTROPHIES

SUPERFICIAL ANTERIOR LAMELLAR

KERATOPLASTY (SALK)
PTK

CORNEAL DYSTROPHIES &

DEGENERATIONS
CORNEA GUTTATA, PPD,

CAVE !!!

CORNEAL DYSTROPHIES &

DEGENERATIONS
PELLUCID MARGINAL DEGENERATION
Peripheral
Thinning
High-Degreee
against the Rule
Progressive Irregular
Astigmatism

CORNEAL DYSTROPHIES &

DEGENERATIONS
PELLUCID MARGINAL DEGENERATION

WEDGE RESECTION &

RELAXING INCISIONS

EXTREME PMCD
79y, Low Vision Since

Years
270 Advanced Peripheral
Thinning with Ectasia
Normal
Thinning

HYDROPS IN PMD
Thinning
Normal

Rare
Descemets Break in the Area of Superior
Thinning
Aqueous Influx into Corneal Stroma

Treatment
Peripheral Corneal Tuck !!!

 No

Results #1

Ectasia
BSCVA=0,4
(-4,00 cyl.@100)

Results #2
Day 1
Postop
No

Ectasia

No

Edema

BSCVA=0,6

CORNEAL DYSTROPHIES &

DEGENERATIONS

Keratoconus

CORNEAL DYSTROPHIES &

DEGENERATIONS
Keratoconus Morphology
Central (Nipple)
Peripheral (Broad Base)

CORNEAL DYSTROPHIES &

DEGENERATIONS

CAVE !!!

KC Should Be Suspected if:

High K-Readings
Asymmetry
20/20 BSCVA Not Possible !!!

KERATOCONUS
High K-Readings

Asymmetry

KERATOCONUS

KC fruste
or
Astigmatism
???

KERATOCONUS
KC Fruste Preop
or
post-LASIK Ectasia
???

Fleischer
Ring !!
!

KERATOCONUS
38-Year Old Patient s/p ICRS x KC
Preop Refraction = -8,50 sph. -7,00 cyl. @ 180

KERATOCONUS
17-Year Old Patient s/p RK x KC !!!
Preop Refraction = - 1,00 sph. - 1,75 cyl. @ 175
Post-RK Refraction = + 1,00 sph. -1,50 cyl. @ 170

CORNEAL DYSTROPHIES
CLASSIC MORPHOLOGIC
(ANATOMIC) CLASSIFICATION
Epithelium (e.g. map-dot-fingerprint)
Bowmans Layer (e.g. Reis-Bckler)
Stroma - Deposition (e.g. Graenouw)
Stroma - Ectasia (e.g. Keratoconus)
Endothelium (e.g. guttata, Fuchs)

Jayne S Weiss, Chair

Michael W Belin, Vice-Chair
Members
Anthony Aldave (US)
Massimo Busin (Italy)
Cecile Bredrup (Norway )
Gordon Klintworth (US)
Walter Lisch (Germany)
Shigeru Kinoshita (Japan)
Terho Kivela (Finland)
Eung Kim (Korea)
Hans Ulrik Moller (Denmark)
Francis Munier (France)
Berthold Seitz (Germany)
John Sutphin (US)
Gabriel Van Rij (Netherlands)
Rasik Vaajpayee (Australia)
Consultants
Tony Bron (UK)
Joseph Frucht-Pery (Israel)
Mark J Mannis (US)
Chris Rapuano (US)

IC D
3

International Committee on
Classification of Corneal Dystrophies
Sponsored by The CORNEA Society

Cornea, Volume 27,

Suppl. 2, December

2008

CORNEAL DYSTROPHIES
NEW IC3D CLASSIFICATION

Morphologic (Anatomic)
Evidence Categories (1 to 4)
Dystrophies with common
genetics grouped together

CORNEAL DYSTROPHIES

EVIDENCE CATEGORIES
1. Well-Defined
Dystrophy
Known
Location,
Gene &
Mutation

CORNEAL DYSTROPHIES

EVIDENCE CATEGORIES
2. Well-Defined
Dystrophy
Known
Location
(Gene?)

CORNEAL DYSTROPHIES

EVIDENCE CATEGORIES
3. Well-Defined
Dystrophy
No Known
Genetics

CORNEAL DYSTROPHIES

EVIDENCE CATEGORIES
4. Suspected
New or Query
Distinct
Dystrophy

CORNEAL DYSTROPHIES

One Disease = Different Genes

CORNEAL DYSTROPHIES

One Gene = Different Diseases

CORNEAL DYSTROPHIES

Beta-Transforming Growth
Factor Induced Gene Human
Clone
(BigH3 or Keratoepithelin)
(Chromosome 5q31)

CORNEAL DYSTROPHIES
BigH3 (Keratoepithelin)

From: Fingert & Stone, in Krachmer, Mannis & Holland: Cornea

CORNEAL DYSTROPHIES
Non - BigH3

From: Fingert & Stone, in Krachmer, Mannis & Holland: Cornea

CORNEAL DYSTROPHIES
WHY IDENTIFY RESPONSIBLE
GENES ???
To develop specific diagnostic tests
(similar disorders, clinical course)
To develop experimental models
To develop genetic treatments
(pharma, gene replacement, gene
suppression)

CORNEAL DYSTROPHIES
GENETIC TREATMENT
Delivery of Recombinant Genes
(Transgenes) to Corneal Tissue
Efficiency of Transgene Delivery
Duration of Transgene Activity
Safety

!!!

CORNEAL DYSTROPHIES

GENETIC TREATMENT
vs
CONVENTIONAL
TREATMENT
(SURGERY)

CORNEAL DYSTROPHIES
PENETRATING KERATOPLASTY

CORNEAL DYSTROPHIES

???

PETERS
ANOMALY

Congenital
Sporadic
Stable

CORNEAL EMBROLOGY
VI Week:
The Optic Cup
Reaches the
Crystalline
Lens

CORNEAL EMBROLOGY
3 Waves of
Undifferentiated

Ectodermic
Tissue

1st = Endothelium

2nd = Stroma

3rd = Angle + Iris

CORNEAL EMBROLOGY
Stepladder
Classification

Waring
1975

CONGENITAL
Anomalies Syndromes

Only
Ocular

Ocular +
Systemic
(Glaucoma)

CONGENITAL ANOMALIES

Epibulbar Dermoid & Goldenhar Syndrome

CONGENITAL ANOMALIES

Embriotoxon

CONGENITAL ANOMALIES

Axenfeld
Anomaly
(Syndrome)

CONGENITAL ANOMALIES

Rieger
Anomaly
(Syndrome)

CONGENITAL ANOMALIES

Keratoconus
Posticus

CONGENITAL ANOMALIES

Keratoconus Posticus
Normal
Endothelium (
2
1900 cell/mm )
VA = 20/20

CONGENITAL ANOMALIES

Peters I
Anomaly
(Syndrome)

CONGENITAL ANOMALIES

Peters II
Anomaly
(Syndrome)

CONGENITAL ANOMALIES

Peters II
Anomaly
(Syndrome)

CONGENITAL ANOMALIES

Peters II
Anomaly
(Syndrome)

CONGENITAL ANOMALIES

Peters II
Anomaly
(Syndrome)

CONGENITAL ANOMALIES

Microcornea
(Nanophthalmos)
(Microphthalmos)

CONGENITAL ANOMALIES

Megalocornea

CONGENITAL ANOMALIES

Buphthalmos
Haab
Striae

STEM CELL DEFICIENCY

MYTH # 6:

CORNEAL NEOVESSELS = SCD

STEM CELL DEFICIENCY

CORNEAL NEOVESSELS

Infections
Chronic
Inflammation
(BK, Loose
Sutures, CL
wear, etc.)

CLINICAL CASE
85-Year-Old Woman, No Surgery
VA = LP
Diffuse Pannus
5-Year History
Ulcer
Inflammation +

CLINICAL CASE
85-Year-Old Woman, No Surgery
Other Eye
Relatively
Normal
Small Pannus
Good VA (0.6)

CLINICAL CASE
85-Year-Old Woman, Rosacea
Treat Rosacea!!!
Systemic & Topical
TETRACYCLINES

Topical
STEROIDS

CLINICAL CASE

5 Years Mushroom PK

STEM CELL DEFICIENCY

FACT # 6:

SCD = EXTREMELY RARE !!!

CONGENITAL SCD

ANIRIDIA
Hereditary

(PAX6)
Sporadic
(Wilms Tumor)

CONGENITAL SCD

PAX6 = SCD
IRIS MAY
BE
NORMAL !!!

ACQUIRED SCD
CHEMICAL
TRAUMAS
(alkali, acids,
etc.)

ACQUIRED SCD
AUTOTRANSPLANT
IN UNILATERAL
LESIONS:
Thoft

1977

Herman

1983

Kenyon

1989

Busin

1994

ACQUIRED SCD

ACQUIRED SCD
AUTOTRANSPLANTATION
DAY 1

ACQUIRED SCD
AUTOTRANSPLANTATION
MONTH 1

ACQUIRED SCD
AUTOTRANSPLANTATION

PREOP
VA = LP

Month 1
VA = HM

Month 4
VA = 0.1

ACQUIRED SCD

AUTOTRANSPLANTATION

4 MONTHS POST SALK

VA = 0.8 !!!

ACQUIRED SCD
AUTOTRANSPLANTATION

PREOP
VA = LP

Month 1
VA = 0.2

Month 4
VA = 0.4

ACQUIRED SCD
AUTOTRANSPLANTATION

PREOP
VA = LP

Year 1
VA = 0.4

ACQUIRED SCD
AUTOTRANSPLANTATION

PREOP
VA = LP

Year 1
VA = 0.1

ACQUIRED SCD
AUTOTRANSPLANTATION

PREOP
VA = LP

Year 1 1/2
VA = 20/200

ACQUIRED SCD
BILATERAL LESIONS
RECOVERY FROM
DONOR
TRANSPLANTATION

SURVIVAL ???

CORNEAL DISEASES

ULTIMATE MYTH:
PERFECT VISION IS THE GOAL

CORNEAL DISEASES

ULTIMATE FACT:
COMPROMISE MAY BE BETTER

BREAK !!
!