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ISSN: 2155-9570

Research Article Open Access

Ophthalmia Neonatorum
Suzanne Katrina V Palafox1, Smitha Jasper1, Tauber1, Allyson D1 and Stephen Foster C1,2*
Massachusetts Eye Research and Surgery Institution, Research Fellow, Massachusetts, USA
1

Massachusetts Eye Research and Surgery Institution, Founder and President, Ocular Immunology and Uveitis Foundation, Founder and President, Harvard Medical
2

School, Clinical Professor of Ophthalmology, USA

Abstract
Ophthalmia neonatorum, inflammation of the conjunctiva with discharge manifesting within the first 28 days of life,
is acquired by the neonate during passage through the infected birth canal. This condition also known as neonatal
conjunctivitis can result in visually disabling complications [1]. The spectrum of infectious pathogens which cause
neonatal conjunctivitis differs in various parts of the world, depending upon the relative prevalence of prenatal maternal
care and the use of prophylactic treatment to prevent infections in the pregnant mother and the newborn infant [3].
The common infectious causes of ophthalmia neonatorum include Chlamydia trachomatis, Staphylococcus aureus,
Staphylococcus epidermis, Escherichia coli, Neisseria gonorrhea, other gram-negative bacteria, and Herpes Simplex
virus [2,6,8]. Data support a high index of suspicion based on history and clinical presentation, various diagnostic
techniques and modes of antimicrobial therapy as all contributory to reducing the occurrence of neonatal conjunctivitis.

Keywords: Neonatal conjunctivitis;  Chlamydia trachomatis; it has been detected in 51.2% of Chinese infants  [14]. Staphylococcus
Staphylococcus aureus; Staphylococcus epidermis; Neisseria gonorrhea; aureus  is the most commonly detected organism in countries like
Escherichia coli; Herpes Simplex virus Argentina (27.6%) [4] and in Hong Kong (36%) [2]. The differences in
results may be due to epidemiological variations in different countries
Epidemiological Features and also be a reflection of the spectrum of sexually transmitted diseases
The beginning of the twentieth century saw the advent of screening prevalent in these respective communities [9] (Table 1).
pregnant females for sexually transmitted diseases (STDs) prior to the Pathophysiology
widespread use of prophylactic eye drops. This period was marked
by the prevalence of neonatal conjunctivitis which was much higher Vertical transmission from the mother is the route of transmission
than today. The World Health Organization (WHO) reports that in to the affected newborn. Both parents, however, should be screened for
1986, the prevalence rate of neonatal conjunctivitis as the cause of STD infection [7,12]. The ocular surface is well-equipped with unique
vision loss in children in European institutions was 20%-79% [16]. Most
Infectious neonatal conjunctivitis occurs in 1-2% of all births, in the Location Authors Year common
United States today [17]. Unfortunately, in underdeveloped countries, pathogen
neonatal conjunctivitis remains a major problem due to inadequate Argentina Di Bartolomeo,Higa, Janer,et.al.4 2005 S.aureus
Chlamydia
maternal care and the lack of widespread use of prophylactic treatment China Wu,Yang,Liu14 2003
trachomatis
to prevent infections immediately following birth [18]. Statistics reveals Schaller, Miño de Kaspar, Chlamydia
Germany 1997
that in developed countries. Schriever, Klauss69 trachomatis
Hong Kong Chang, Cheng, Kwong2 2006 S.aureus
Overall, infectious conjunctivitis occurs in 12% of neonates, and Laga, Plummer, Nzanze,
Namaara,Brunham, Ndinya- Chlamydia
23% of neonates are afflicted with this condition in developing nations Kenya
Achola,Maitha,Ronald, D’Costa,
1986
trachomatis
[10,19]. Laga et al. report that in a Nairobi hospital wherein no ocular Bhullar, et.al.10
prophylaxis against ophthalmia neonatorum was used, the incidence of Sergiwa,Pratt,Eren,Sunona,
Chlamydia
ophthalmia neonatorum was 23.2 per 100 live births, and incidences Thailand 1993 trachomatis,
Hart 70
S.aureus
of gonococcal and chlamydial ophthalmia were 3.6 and 8.1 per 100 Nsanze, Dawodu ,Usmani ,
United Arab Emirates 1996 S.aureus
live births, respectively. The infectious agents responsible, in order of Sabarinathan, Varady71
frequency, were C. trachomatis (31%), N gonorrhea (12%), and both Chlamydia
United States O’Hara12 1993
trachomatis
(3%) in 181 cases of neonatal conjunctivitis. Data encompassing 67
neonates exposed to maternal gonococcal infection and 201 exposed to Table 1: Vertically-transmitted neonatal conjunctivitis.
maternal chlamydial infection showed rates of transmission to the eye
of 42% and 31%, respectively [10].
De Schryver et. al (1990) reported that 1-5% of newborns *Corresponding author: Stephen Foster C, 5 Cambridge Center, 8th Floor,
globally are at risk of gonococcal ophthalmia neonatorum [18]. Cambridge, Massachusetts 02142, USA, Tel: 6174941431; E-mail: sfoster@mersi.
us
C.trachomatis  has replaced N.gonorrhea  as the most important single
etiology even in developing countries, causing up to 32% of all Received  September 29, 2010; Accepted December 23, 2010; Published
December 27, 2010
cases  [20,29]. The transmission rate from an infected mother to the
newborn has been reported to range from 30-45% for N.gonorrhea and Citation: Palafox SKV, Jasper S, Tauber, Allyson D, Foster SC (2011) Ophthalmia
30% for C.trachomatis [7,20]. Chlamydial infections are the most Neonatorum. J Clinic Experiment Ophthalmol 2:119. doi:10.4172/2155-9570.1000119
common STDs in the United States [35,36] It is also the most frequently Copyright: © 2011 Palafox SKV, et al. This is an open-access article distributed
identifiable infectious cause of ophthalmia neonatorum, with an under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
incidence of 8.2/1000 births [12] . Wu et al. [14] reported that in China, original author and source are credited.

J Clinic Experiment Ophthalmol

ISSN:2155-9570 JCEO an open access journal Volume 2 • Issue 1 • 1000119
Citation: Palafox SKV, Jasper S, Tauber, Allyson D, Foster SC (2011) Ophthalmia Neonatorum. J Clinic Experiment Ophthalmol 2:119. doi:10.4172/2155-
9570.1000119
anatomic and functional features that prevent bacterial infection in the
healthy eye, both in infants and adults. Immunoglobulins, lysozyme,
complement, and multiple antibacterial enzymes are found in tears. The
tear film that is continuously being replenished creates an environment
that makes it very difficult for bacteria to thrive. Basically, it is through
successful invasion that N.gonorrhea overcomes intact epithelial
barriers [62].  Fortunately, most bacteria rely on a break in the barrier
function. Bacterial exotoxins such as those found in Streptococcus and
Staphylococcus species can induce necrosis. While most pathogens
are cleared from the site of infection in the acute phase; some strains
can persist. C. trachomatis for example survives and persists within
intracellular phagosomes [62].
C. trachomatis serotyping is based on immunogenic epitope analysis
of the major outer membrane protein (MOMP), and it differentiates 18
serovars. Among these, serovars A to C are associated with trachoma;
serovars D to K are common in adult urogenital and ocular infections,
in both adults and neonates alike. Although these facts have long been
established, it was only recently that serovar E was determined to be the
most frequently detected serovar (71%) in neonatal ocular samples in a
Buenos Aires community [66].
Clinical Picture
The signs and symptoms of ophthalmia neonatorum are similar for
most of the infectious agents and they include injection of the conjunctiva
associated with periorbital edema and purulent discharge [5]. Though a
self-limiting disease, it has the potential to have serious consequences
including severe keratopathy and serious systemic involvement if left
untreated [13,15]. Early detection and specific treatment are therefore
of utmost importance to prevent the complications of these infants.
This type of conjunctivitis is inflammation of the conjunctiva with
discharge, typically manifesting within the first month of life. Because
neonatal conjunctivitis may result from varied causes, it is necessary to
make an accurate diagnosis in order to begin appropriate treatment.
Proper treatment directed at each specific cause can help minimize
complications and loss of vision.
Neonatal conjunctivitis may be infectious, caused by bacterial,
chlamydial, viral, or fungal pathogens, or can be inflammatory and
non-infectious, caused by prophylactic silver nitrate solution. The
silver nitrate as a prophylactic agent does cause chemical conjunctivitis,
especially when the concentration of the chemical becomes toxic in
tropical countries [5]. An important differential diagnosis includes
preseptal cellulitis, but empiric treatment for bacterial pathogens is
likely to be effective for cellulitis as well.
Despite their immature immune system, neonates are infrequently
infected during their passage through the birth canal. Traumatic delivery
or premature rupture of maternal membranes may increase the risk of
infection. The presence of active cervical or vaginal maternal infection
markedly increases the risk of neonatal conjunctivitis. Cervical infection
with gonorrhea results in positive cultures from neonatal conjunctiva in
30-50% of cases [20]. Cervical infection with Chlamydia carries a risk
to the neonate to 18-50%, and active vaginal herpes infection carries a
low risk of transmission to newborns, but studies are limited [21-24].
However, the risk of transmission in cases of recently acquired genital
herpes may be as high as 48% [25] .The differences may be due to
epidemiological variations in different countries and also be a reflection
of the spectrum of sexually transmitted diseases prevalent in these
communities [23]. Pseudomembranes or true membranes may occur
and lead to scarring if untreated [39,40]. Untreated disease can lead to
chronic infection lasting many months [41].Vision loss is usually due to
eyelid scarring and consequent corneal pannus. Systemic development
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Page 2 of 5
of Chlamydial pneumonitis, otitis, and pharyngeal involvement has
been reported [42]. A majority of infants with chlamydial conjunctivitis
develop chlamydial pneumonitis: approximately 50% of infants with
chlamydial pneumonitis have concurrent conjunctivitis or a recent
history of conjunctivitis [63].
Other bacterial causes of neonatal conjunctivitis include
Hemophilus, Staphylococcal and Streptococcal species and Neisseria
gonorrhea. Often described as “hyperacute conjunctivitis,” the
incubation period for Neisseria gonorrhea may be as short as 1-7 days
[37,38]. Infection is more often bilateral and signs are more severe
than nongonococcal infections. Early serosanguinous exudate may
be replaced by copious mucopurulent discharge within 24 hours and
membranes may be seen. Marked eyelid swelling, injection and swelling
of the conjunctiva are common and corneal involvement is seen in 16%
of cases [62] (Figure1). Untreated infections can rapidly progress to
corneal ulceration, perforation and endophthalmitis. Infected infants
may also have other localized gonococcal infections such as rhinitis
and proctitis. A disseminated gonococcal infection with arthritis,
meningitis, pneumonia and sepsis that may lead to death of an infant is
fortunately, very rare [62].
There have been very few publications about hospital-acquired
conjunctivitis (Table 2). In a neonatal intensive care unit (NICU),
the most common isolated in patients with conjunctivitiscoagulase-
negative staphylococci and Klebsiella species [28]. Tarabishy et al. [63]
found 30% of children developed bacterial conjunctivitis after two days
of hospitalization at the Cleveland Clinic harbored gram-organisms.
The rate of methicillin resistance in patients with Staphylococcus
species-conjunctivitis was noted to be higher in those hospitalized more
than two days than those Staphylococcus species who were hospitalized
for less than two days. This leads one to surmise that among NICU
inpatients, the pathogens causing conjunctivitis are not the usual
suspects in the outpatient setting [63] (Table2).
Diagnostic Modalities
Proper and definitive diagnosis of the cause of neonatal conjunctivitis
depends on laboratory identification of the causative organism. The
Figure 1: Gonococcal conjunctivitis of the newborn. This is acquired
during passage through the birth canal and occurs a few days after birth.
A mucopurulent discharge is usually present. Gram staining reveals
intraepithelial Gram-negative diplococci. Aggressive treatment with systemic
and topical antibiotics is indicated, as severe corneal ulceration can occur.
Location Authors Year Most common pathogen
Sarvikivi,Karki,Lyytikäinen,the S.agalactiae(early onset);S.
Finland Finnish NICU Prevalence 2010 aureus,coagulase-negative
Study Group72 staphylococci,E.coli(late onset)
Borer,Riven,Golan,Ode
coagulase-negative
Israel s,Zmora,Raz,Melamed, 2010
staphylococci
Plakht,Peled 73
Table 2: Hospital-acquired neonatal conjunctivitis.
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Citation: Palafox SKV, Jasper S, Tauber, Allyson D, Foster SC (2011) Ophthalmia Neonatorum. J Clinic Experiment Ophthalmol 2:119. doi:10.4172/2155-
9570.1000119
AUTHOR and DATE METHODS PARTICIPANTS and SETTING
Table 3: (Characteristics of included studies) from the article: “A meta-analysis of the efficacy of ocular prophylactic agents used for the prevention of gonococcal and
chlamydial ophthalmia neonatorum.”
speed of progression characteristic of N.gonorrhea conjunctivitis
makes it imperative to perform smears, as it may be possible to identify
gram-negative diplococci and initiate proper treatment within hours.
Gram staining of conjunctival swabs may be positive in up to 100%
of gonococcal infections [48,49]. Giemsa staining may be helpful in
identifying types of inflammatory cells, but is unlikely to provide
definitive diagnostic information [50,51]. Other non-culture methods
such as direct fluorescent antibody testing, enzyme immunoassays and
nucleic acid testing (NAT) may allow early detection of Chlamydia
within hours rather than several days, as required for culture methods
[52].
These tests are not widely available and not FDA-approved for use
on conjunctival samples [53].Traditional culture methods include the
use of appropriate media (blood agar, chocolate agar or Thayer-Martin
media and thioglycolate broth). Because Chlamydia is an intracellular
parasite, it is necessary to grow cultures using tissue culture media and
examine for the presence of intracellular inclusions [54].
Management
Prophylactic treatment to reduce the incidence of neonatal infectious
conjunctivitis began with the use of silver nitrate, proposed by Crede in
1881 [26]. Effective at inactivating gonococci by agglutination, silver
nitrate caused a transient, mild conjunctival inflammation in over 90%
of treated eyes, characterized by redness and tearing that resolved within
24-48 hours [27,28]. More recently, prophylactic treatment has shifted
to the use of erythromycin in the United States, which is well tolerated.
Povidone-iodine is increasingly used elsewhere, however [68]. A recent
meta-analysis has found in their review that both erythromycin and
povidone-iodine are more effective than silver nitrate in the prevention
of chlamydial ophthalmia neonatorum. This finding however comes
with a warning that the evidence might not be sufficient (see Table 3,
permission pending).
Treatment of neonatal conjunctivitis should be initially based on the
history, clinical presentation and results of smears. Later, as laboratory
results become available, specific therapy can be instituted.
Given the high incidence of extra-ocular infection in neonates with
Chlamydia conjunctivitis, systemic therapy is appropriate. A fourteen day
course of twice-daily oral erythromycin has been reported to eliminate
Chlamydial infection in 80-100% of patients. The CDC recommends
dosing at 50 mg/kg/day in four divided doses for two weeks [55]. Failure
to respond to this course is grounds for repeating the fourteen courses
before changing therapy to trimethoprim-sulfamethoxazole 0.5 ml/kg/
day in two doses daily for two weeks [56]. Macrolide antibiotics such as
azithromycin, clarithromycin and roxithromycin may be more effective
against Chlamydial infections [57], but have not been well studied in
neonatal Chlamydial conjunctivitis. The results of one study involving a
limited number of patients suggest that a short course of azithromycin,
20 mg/kg/day orally, 1 dose daily for 3 days, may be effective [58].
Gonococcal conjunctivitis can be treated with ceftriaxone 50 mg/
kg/day given either intramuscularly or intravenously, or as a single dose
treatment of 125mg [25,35,59]. Alternative therapies include cefotaxime
100mg intramuscularly or 25 mg/kg given either intramuscularly or
intravenously every 12 hours for 7 days [58,61].
Herpetic conjunctivitis can be treated with topical trifluridine
1% solution given every two hours for 14 days and should not be
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 INTERVENTIONS OUTCOMES SUMMARY OF FINDINGS
administered for more than 21 days because of potential corneal
epithelial toxicity, blepharitis, cannicular occlusion, and allergies
[47,50,67],. First-line therapy for acute superficial herpetic keratitis
outside the United States employs ganciclovir ophthalmic gel, 0.15%,
applied five times a day for ten days. Another study suggests using this
gel five times daily until the corneal ulcer heals, then three times daily
for a week [67] . Many pediatricians also use either oral acyclovir 30
mg/kg/day for 10 days or intravenous acyclovir 10 mg/kg or 500 mg/m2
every 8 hours for 10 days [50].
The diagnosis of neonatal conjunctivitis must be made promptly to
facilitate rapid initiation of effective therapy. It cannot be overemphasized
how primary healthcare workers, obstetrics-gynecology specialists,
neonatologists, ophthalmologists and other medical staff should be
educated and made aware about the global impact of this disease.
Ophthalmia neonatorum is a major preventable cause of childhood
blindness and with efforts on all levels, this can be eradicated.
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Concepts, pp 114-7. American Academy of Ophthalmology-Lifelong Education
for the Ophthalmologist.
63. Tarabishy AB, Jeng BH (2008) Bacterial conjunctivitis: a review for internists.
Cleve Clin J Med 75: 507-512.
64. Tarabishy AB, Hall GS, Procop GW, Jeng BH (2006) Bacterial culture isolates
from hospitalized pediatric patients with conjunctivitis. Am J Ophthalmol 142:
678-680.
65. Gallo Vaulet L, Entrocassi C, Corominas AI, Rodríguez Fermepin M (2010)
Distribution study of Chlamydia trachomatis genotypes in symptomatic patients
in Buenos Aires, Argentina: association between genotype E and neonatal
conjunctivitis. BMC Res Notes 3: 34.
66. Fermepin MR, Entrocassi AC, Sauka DH, Vaulet ML, Corominas AI (2007)
Chlamydia trachomatis serovars in Buenos Aires, Argentina: predominance of
serovar E in ophthalmia neonatorum. Sex Transm Dis 34: 1041.
Volume 2 • Issue 1 • 1000119
Citation: Palafox SKV, Jasper S, Tauber, Allyson D, Foster SC (2011) Ophthalmia Neonatorum. J Clinic Experiment Ophthalmol 2:119. doi:10.4172/2155-
9570.1000119
67. Colin J (2007) Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating
ocular herpes. Clinical Ophthalmology 1: 441-453.
68. Darling EK, McDonald H (2010) A meta-analysis of the efficacy of ocular
prophylactic agents used for the prevention of gonococcal and chlamydial
ophthalmia neonatorum. J Midwifery Womens Health 55: 319-327.
69. Schaller U, Miño de Kaspar H, Schriever S, Klauss V (1997) Ophthalmia
neonatorum caused by Chlamydia trachomatis. Rapid diagnosis and therapy.
Der Ophthalmologe 94: 317-320.
70. Sergiwa A, Pratt BC, Eren E, Sunona TC, Hart CA (1993) Ophthalmia
neonatorum in Bangkok: the significance of Chlamydia trachomatis. 13: 233-
236.
J Clinic Experiment Ophthalmol
ISSN:2155-9570 JCEO an open access journal
Page 5 of 5
71. Nsanze H, Dawodu A, Usmani A, Sabarinathan K, Varady E (1996) Ophthalmia
neonatorum in the United Arab Emirates. Ann Trop Paediatr 16: 27-32.
72. Sarvikivi E, Karki T, Lyytikainen O; Finnish NICU Prevalence Study Group
(2010) Repeated prevalence surveys of healthcare-associated infections in
Finnish neonatal intensive care units. J Hosp Infect 76: 156-60.
73. Borer A, Livshiz-Riven I, Golan A, Saidel-Odes L, Zmora E, et al. (2010)
Hospital-acquired conjunctivitis in a neonatal intensive care unit: Bacterial
etiology and susceptibility patterns. Am J Infect Control 38: 650-652.
74. Cornea Atlas (2nd edition), figure 6.37, Krachmer JH, Palay DA, Mosby-Elsevier
(2005), Philadelphia, USA.
Volume 2 • Issue 1 • 1000119
enters the optic nerve about 8–15 mm behind the globe. Other branches of the
ophthalmic artery include the lacrimal artery, supplying the lacrimal gland and
upper lid; muscular branches to the various muscles of the orbit; long and short
posterior ciliary arteries; medial palpebral arteries to both lids; and the
supraorbital and supratrochlear arteries. The short posterior ciliary arteries
supply the choroid and parts of the optic nerve. The two long posterior ciliary
arteries supply the ciliary body and anastomose with each other and with the
anterior ciliary arteries to form the major arterial circle of the iris. The anterior
ciliary arteries are derived from the muscular branches to the rectus muscles.
They supply the anterior sclera, episclera, limbus, and conjunctiva and contribute
to the major arterial circle of the iris. The most anterior branches of the
ophthalmic artery contribute to the formation of the arterial arcades of the lids,
which make an anastomosis with the external carotid circulation via the facial
artery.
The venous drainage of the orbit is primarily through the superior and inferior
ophthalmic veins, into which drain the vortex veins, the anterior ciliary veins,
and the central retinal vein. The ophthalmic veins communicate with the
cavernous sinus via the superior orbital fissure and the pterygoid venous plexus
via the inferior orbital fissure. The superior ophthalmic vein is initially formed
from the supraorbital and supratrochlear veins and from a branch of the angular
vein, all of which drain the skin of the periorbital region. This provides a direct
communication between the skin of the face and the cavernous sinus, thus
forming the basis of the potentially lethal cavernous sinus thrombosis, secondary
to superficial infection of the periorbital skin.

THE EYEBALL

The normal adult globe is approximately spherical, with an anteroposterior

diameter averaging 24 mm.

THE CONJUNCTIVA

The conjunctiva is the thin, transparent mucous membrane that covers the
posterior surface of the lids (the palpebral conjunctiva) and the anterior surface

23
of the sclera (the bulbar conjunctiva). It is continuous with the skin at the lid
margin (a mucocutaneous junction) and with the corneal epithelium at the
limbus.
The palpebral conjunctiva lines the posterior surface of the lids and is firmly
adherent to the tarsus. At the superior or inferior margin of the tarsus, the
conjunctiva is reflected posteriorly (at the superior and inferior fornices) and
covers the episcleral tissue to become the bulbar conjunctiva.
The bulbar conjunctiva is loosely attached to the orbital septum in the
fornices and is folded many times. This allows the eye to move and enlarges the
secretory conjunctival surface. (The ducts of the lacrimal gland open into the
superior temporal fornix.) Except at the limbus (where Tenon’s capsule and the
conjunctiva are fused for about 3 mm), the bulbar conjunctiva is loosely attached
to Tenon’s capsule and the underlying sclera.
A soft, movable, thickened fold of bulbar conjunctiva (the semilunar fold) is
located at the inner canthus and corresponds to the nictitating membrane of some
lower animals. A small, fleshy, epidermoid structure (the caruncle) is attached
superficially to the inner portion of the semilunar fold and is a transition zone
containing both cutaneous and mucous membrane elements.

Histology

The conjunctival epithelium consists of two to five layers of stratified columnar

epithelial cell—superficial and basal. Conjunctival epithelium near the limbus,
over the caruncle, and near the mucocutaneous junctions at the lid margins
consists of stratified squamous epithelial cells. The superficial epithelial cells
contain round or oval mucus-secreting goblet cells. The mucus, as it forms,
pushes aside the goblet cell nucleus and is necessary for proper dispersion of the
precorneal tear film. The basal epithelial cells stain more deeply than the
superficial cells and may contain pigment near the limbus.
The conjunctival stroma is divided into an adenoid (superficial) layer and a
fibrous (deep) layer. The adenoid layer contains lymphoid tissue and, in some
areas, may contain “follicle-like” structures without germinal centers. The
adenoid layer does not develop until after the first 2 or 3 months of life. This
explains why in the newborn inclusion conjunctivitis is papillary, whereas
thereafter it is follicular. The fibrous layer is composed of connective tissue that
attaches to the tarsal plate. This explains the appearance of the papillary reaction
in inflammations of the conjunctiva. The fibrous layer is loosely arranged over

24
the globe.
The accessory lacrimal glands (glands of Krause and Wolfring), which
resemble the lacrimal gland in structure and function, are located in the stroma.
Most of the glands of Krause are in the upper fornix, and the remainder are in the
lower fornix. The glands of Wolfring lie at the superior margin of the upper
tarsus.

Blood Supply, Lymphatics, & Nerve Supply

The conjunctival arteries are derived from the anterior ciliary and palpebral
arteries. The two arteries anastomose freely and—along with the numerous
conjunctival veins that generally follow the arterial pattern—form a considerable
conjunctival vascular network. The conjunctival lymphatics are arranged in
superficial and deep layers and join with the lymphatics of the lids to form a rich
lymphatic plexus. The conjunctiva receives its nerve supply from the first
(ophthalmic) division of the fifth nerve. It possesses a relatively small number of
pain fibers.

TENON’S CAPSULE (FASCIA BULBI)

Tenon’s capsule is a fibrous membrane that envelops the globe from the limbus
to the optic nerve (see Figure 1–19). Adjacent to the limbus, the conjunctiva,
Tenon’s capsule, and episclera are fused together. More posteriorly, the inner
surface of Tenon’s capsule lies against the sclera, and its outer aspect is in
contact with orbital fat and other structures within the extraocular muscle cone.
At the point where Tenon’s capsule is pierced by tendons of the extraocular
muscles in their passage to their attachments to the globe, it sends a tubular
reflection around each of these muscles. These fascial reflections become
continuous with the fascia of the muscles, the fused fasciae sending expansions
to the surrounding structures and to the orbital bones. The fascial expansions are
quite tough and limit the action of the extraocular muscles, and are therefore
known as check ligaments (see Figure 1–20). They regulate the direction of
action of the extraocular muscles and may act as their functional mechanical
origins, possibly with active neuronal control (active pulley hypothesis). The
lower segment of Tenon’s capsule is thick and fuses with the fascia of the
inferior rectus and the inferior oblique muscles to form the suspensory ligament

25
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The clear tissue covering the white part of your eye and the inside of your eyelids.

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4/29/2019 Anatomy of cornea and ocular surface

Indian J Ophthalmol. 2018 Feb; 66(2): 190–194. PMCID: PMC5819093

doi: 10.4103/ijo.IJO_646_17: 10.4103/ijo.IJO_646_17 PMID: 29380756

Anatomy of cornea and ocular surface

Mittanamalli S Sridhar

Department of Ophthalmology, Krishna Institute of Medical Sciences, Hyderabad, Telangana, India

Correspondence to: Dr. Mittanamalli S Sridhar, Department of Ophthalmology, Krishna Institute of Medical
Sciences, Minister Road, Secunderabad, Hyderabad - 500 003, Telangana, India. E-mail: sri.vision@yahoo.co.in

Received 2017 Jul 26; Accepted 2017 Sep 20.

Copyright : © 2018 Indian Journal of Ophthalmology

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-
ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as
the author is credited and the new creations are licensed under the identical terms.

Abstract
Important functions of cornea in the eye include protecting the structures inside the eye, contributing to the
refractive power of the eye, and focusing light rays on the retina with minimum scatter and optical
degradation. Considerable advances have taken place in understanding the organization of collagen in the
corneal stroma and its clinical significance. In this review, the structure and function of various
components of cornea and ocular surface are presented.

Keywords: Collagen, cornea, Descemet's membrane, endothelium, epithelium, stroma

Cornea and sclera constitute the outer covering or coat of the eyeball. The main purpose of this coat is to
protect structures inside the eye. The cornea is a transparent avascular tissue that acts as a structural barrier
and protects the eye against infections.[1] Along with the tear film, it provides proper anterior refractive
surface for the eye. Cornea contributes to two-third of the refractive power of the eye.

The cornea is horizontally oval, measuring 11–12 mm horizontally and 9–11 mm vertically. The corneal
horizontal diameter (white to white) using ORBSCAN II system has revealed average corneal diameter as
11.71 ± 0.42 mm. The average corneal diameter was 11.77 ± 0.37 in males compared to 11.64 ± 0.47 in
females. The corneal diameter ranged from 11.04–12.50 in males and 10.7–12.58 in females.[2] The
limbus is widest in superior and inferior cornea. Cornea is convex and aspheric. The anterior curvature is
7.8 mm and posterior curvature is about 6.5 mm. Cornea contributes to about 40–44 D of refractive power
and accounts for approximately 70% of total refraction. The refractive index of cornea is 1.376. There is a
gradual increase in thickness from central cornea to the periphery[3] [Fig. 1]. Alteration in tissue thickness
is due to increase in the amount of collagen in the peripheral stroma. With different methods of evaluation,
the central corneal thickness in normal eyes is found to range from 551 to 565 μ and the peripheral corneal
thickness from 612 to 640 μ.[4] The corneal thickness is found to decrease with age. Anterior corneal
stromal rigidity appears to be particularly important in maintaining the corneal curvature. Anterior
curvature resists changes to stromal hydration much more than posterior stroma.[1]

The cornea is made up of cellular and acellular components. The cellular components include the epithelial
cells, keratocytes, and endothelial cells. The acellular component includes collagen and
glycosaminoglycans. The epithelial cells are derived from epidermal ectoderm. The keratocyte and
endothelial cells are derived from neural crest. The corneal layers include epithelium, Bowman's layer,

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stroma, Descemet's membrane, and endothelium [Fig. 2]. Recently, a layer of cornea which is well defined,
acellular in pre-Descemet's cornea is getting attention with the development of lamellar surgeries.[5]
Table 1 summarizes all layers of cornea with their functions.

The corneal epithelium is composed fairly uniformly of 5–7 layers of cells [Fig. 3]. It is about 50 μ in
thickness. The epithelium is uniform to provide a smooth regular surface and is made up of nonkeratinized
stratified squamous epithelium. The epithelium is derived from surface ectoderm between 5 and 6 weeks
of gestation. The epithelium and the overlying tear film have symbiotic relationship. The mucin layer of
the tear film which is in the direct contact with corneal epithelium is produced by the conjunctival goblet
cells. It interacts closely with the corneal epithelial cells' glycocalyx to allow hydrophilic spreading of the
tear film with each eyelid blink.

Cornea epithelial cells have a lifespan of 7 to 10 days undergoing involution, apoptosis, and desquamation.
The presence of high concentrations of intracytoplasmic enzyme crystalline, like in lens epithelial cells,
may play an important role in maintaining optical transparency. The epithelium is 5–6 layers structure with
three types of cells: superficial cells, wing cells, and the basal cells. The superficial cells are 2–3 layers
made up of flat polygonal cells. They have a diameter of 40–60 μ with a thickness of about 2–6 μ. The
microvilli on the surface increase the surface area. The epithelial layer is made up of large dark cells and
small light cells. Desmosomes form the tight junction in between the superficial cells. Thawing cells are
2–3 layered and are named as they have wing-like shape. They express 64-k dalton keratins. Basal cells are
single layer of the epithelium which is cuboidal or columnar. They have abundant organelles and they are
active mitotically.

The surface cells maintain tight junction complexes between the neighbors which prohibit tears from
entering the intercellular spaces. The deepest cell layer of the epithelium is the basal layer, which
compromises the single cell layer of epithelium approximately 20 μ tall. Besides the stem cells and
transient amplifying cells, basal cells are the only corneal epithelial cells capable of mitosis. They are the
source of wing and superficial cells.

Desmosomes are present along the lateral membranes of all epithelial cells, to keep the epithelial cells
adherent to each other. The basal cells are attached to the underlying basement membrane by a
hemidesmosomal system. The strong attachment prevents the epithelium getting separated from the
underlying layers. Abnormality of this attachment results in corneal erosions and nonhealing epithelial
defects.

Tight junctions are present only in the lateral wall of apical cells of epithelium, providing a permeability
barrier between the cells at the most superficial level.[3] Adherens junctions are present along the lateral
membrane of only the apical cells of the epithelium. They maintain cellular adherence in the region of tight
junctions. Gap junctions are permeable channels on the lateral aspects of all epithelial cells, allowing the
diffusion of small molecules.

The basement membrane of epithelial cells is 40–60 nm in thickness and is made up of Type IV collagen
and laminin secreted by basal cells. The basement membrane is made up of lamina lucida and lamina
densa. From the basal epithelial cells, anchoring fibrils pass through the basement membrane and end as
anchoring plaques. The anchoring fibrils are made up of Type VII collagen and anchoring plaque is made
up of Type I collagen [Fig. 4]. If basement membrane is damaged, fibronectin levels increases and the
process of healing can take up to 6 weeks.

There are differences between epithelium of central and peripheral cornea. In the central cornea, the
epithelium has 5–7 layers. The basal cells are columnar. There are no melanocytes or Langerhans cells.
There is a smooth basal cell layer with keratan sulfate, and there are no lymphatics. In the peripheral
cornea, the epithelium is 7–10 layered. The basal cells are cuboidal. There are melanocytes and
Langerhans cells. There are undulating extensions of basal layer. There is no keratan sulfate and there are
no lymphatics.

Thoft and Friend proposed the XYZ hypothesis of central epithelial maintenance.[6] X component denotes
the basal cell proliferation. The Y component migration of cells from peripheral to central cornea and Z
component denotes the loss of cells from the surface. The cells in the limbus are in two compartments. The
stem cells and transient amplifying cells are in the proliferative compartment. The postmitotic cells and
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terminally differentiated cells are in nonproliferative compartment. The palisades of Vogt are undulations
in basement membrane which provide increased vascularity, increased surface area for attachment, and
also for provide protection to stem cells.

Bowman's membrane is condensation of collagen and proteoglycans. It is a 12 μ structure and is made up

of Type I and V collagen as well as proteoglycans. It has no regenerative ability. Bowman's membrane lies
just anterior to stroma and is not a true membrane. It is acellular condensate of the most anterior portion of
the stroma. This smooth layer helps the cornea maintains its shape. When injured, this layer does not
regenerate and may result in a scar.

The corneal stroma forms the bulk of the structural framework of the cornea and comprises approximately
80%–85% of its thickness. Embryologically, it is the result of second wave of neural crest migration that
occurs in the 7th week of gestation, after establishment of the primitive endothelium. The stroma is
characteristically transparent which is the result of precise organization of stromal fibers and extracellular
matrix (ECM). The collagen within corneal fibrils is predominantly Type I. Type VI collagen and Type XII
collagen are also found in stroma.[7]

The collagen fibers are arranged in parallel bundles called fibrils. These fibrils are packed in layers or
lamellae. The stroma of the human eye contains 200–250 distinct lamellae, each layer arranged at right
angles relative to fibers in adjacent lamella. The collagen in the stroma is laid down within lamellae. These
structures are of the variable thickness, in humans up to 0.2 mm broad and 2 μm thick. At the center of the
human cornea, there is approximately 200 lamellar thickness. The packing density is higher in the anterior
lamellae than in the posterior stroma. These anterior lamellae are highly interwoven and most appear to
insert into the Bowman's layer.[8] The mid-stromal lamellae are also highly interlaced. The posterior
lamellae in the central cornea are more hydrated. The posterior stromal can swell easily whereas the more
interwoven cannot.

Cornea lamellae in the deepest stroma have preferred directions which appear to close to inferior superior
and nasal-temporal directions. X-rays scattering also has suggested a network of collagen lamella that
enters the cornea close to the inferior, superior, nasal, and temporal which probably originate in the
adjacent sclera. Collagen fibrils in the prepupillary appear to be more closely packed than in the peripheral
cornea.[9] High packing density of stress-bearing collagen fibrils in the prepupillary cornea seems to be
necessary for maintaining corneal strength and hence curvature in a region of reduced corneal thickness.

Collagen fibrils within the cornea are narrower than in many other connecting tissues, and there is an
important factor for transparency, which is a function of diameter. There are about 300–400 triple-helical
molecules within the cross section of the fibril. Ultrastructure within the organization of the lamellar
appears to vary based on the depth within the stroma. Deeper layers are more strictly organized than
superficial layers. This accounts for care of surgical dissection in a particular plane as one approaches the
posterior depths of the corneal stroma.[1] During air injection into stroma, it is a common observation that
part of the posterior stroma often adheres to the Descemet's membrane and there is a natural cleavage
plane in the stroma almost 10 μ alone Descemet's membrane.[5]

A high refractive index and symmetric curvature are essential for optimal refractive power and minimum
astigmatism of the cornea.[10] The architecture of the most anterior part (100–120 μ) of the stroma
prevents changes in the morphology of the stromal region even after extreme swelling. The smooth
curvature at the anterior side is not affected in conditions with increased corneal hydration. As the
diameter of the cornea hardly changes, swelling is compensated by large undulations in Descemet's
membrane at the posterior side. The corneal swelling behavior shows a gradual decrease in swelling from
posterior to anterior side; this seems to be related to the organization of collagen lamellae and to the
presence of different types of proteoglycan. In the posterior part keratan sulfate, a more hydrophilic
proteoglycan is prevalent, whereas in the anterior part dermatan sulfate, a much less hydrophilic
proteoglycan is prevalent. There is also an elastic fiber network within the stroma. These elastic fibers
present throughout the stromal depth, are concentrated below the posterior-most keratocyte layer.

Cornea stroma is made up of keratocytes and ECM. The ECM is composed of collagens (Type I, III, V, VI)
and glycosaminoglycans. The glycosaminoglycans constitute keratan sulfate, chondroitin sulfate, and
dermatan sulfate. The corneal stroma has keratocytes and about 300 collagen lamellae which are regularly

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arranged. The glycosaminoglycans are predominantly keratan sulfate. Less contribution is by dermatan
sulfate and chondroitin sulfate. Hyaluronan is seen in infancy.

Keratocytes are the major cell type of stroma. They are involved in maintaining the ECM environment.
They are able to synthesize collagen molecules and glycosaminoglycans, while also creating matrix
metalloproteinases (MMPs), all important in maintaining stromal homeostasis. Most of the keratocytes
reside in the anterior stroma.

The Descemet's membrane is a 7 μ structure. It is made up of Type IV collagen and laminin. Descemet's
membrane begins in utero at the 8-week stage. Endothelial cells continuously secrete Descemet's
membrane. The anterior 3 μ secreted before birth has a distinctive banded appearance. Descemet's
membrane produced after birth is unbanded and has an amorphous ultrastructural texture. Descemet's
membrane can be up to 10 μ in thickness with age. The Descemet's membrane is elastic and curls on
getting severed.

The endothelium is a single layer, 5 μ thick structure [Fig. 5]. The cells are hexagonal and are
metabolically active. There is an endothelial pump which regulates water content. Endothelium is a
monolayer which appears as a honeycomb-like mosaic when viewed from the posterior side. In early
embryogenesis, the posterior surface is lined with a neural crest-derived monolayer of orderly arranged
cuboidal cells. The individual cells continue to flatten over time and stabilize at approximately 4 μ in
thickness is adulthood. Adjacent cells share extensive lateral interdigitations and possess gap and tight
junctions along the lateral borders. The lateral membrane contains the high density of Na+ K+ ATPase
pump sites. The two most important ion transport systems are the membrane-bound Na+ K+ ATPase and
the intracellular carbonic anhydrase pathway. Activity in both these pathways produces the net flux of ions
from the stroma to the aqueous humor. The basal surface of the endothelium contains numerous
hemidesmosomes that promote adhesion to Descemet's membrane.

Immediately anterior to the flattened layer of endothelial cell is a discontinuous homogeneous acellular
layer Descemet's membrane. At birth, the endothelial layer is approximately 10 μ thick. Descemet's
membrane becomes continuous and uniform, fusing peripheral with the trabecular beams. The fusion site,
known as Schwalbe line, is a gonioscopic landmark that defines the end of Descemet's membrane and the
start of trabecular meshwork.

Endothelial cell density continues to change throughout life, from second to eight decades of life. The cell
density declines from 3000 to 4000 cells/mm2 to around 2600 cells/mm2 of hexagonal cells decline from
approximately from 75% to 60%. Endothelial cell density at birth is 3500 cells/mm2. Human central
endothelial cell density decreases at an average of approximately 0.6% per year in normal corneas
throughout adult life, into gradual increase in polymegathism and pleomorphism.[11] Endothelial cells do
not regenerate in adults.[12]

A deep corneal layer has been getting attention recently. It is a well-defined, acellular, strong layer in the
pre-Descemet's cornea.[5] This layer is found to be 5–8 lamellae of collagen fibers ranging from 6 to 15 μ
in thickness. There are no keratocytes in this layer, and it is impervious to air. In donor eyes from eye
banks, the bubble can be inflated to pressure about 700 mmHg before it ruptures. It is also found in
children.

The cornea is one of the most heavily innervated and most sensitive tissues in the body. The sensation is
derived from the nasociliary branch of the first division of (ophthalmic) of the trigeminal nerve. Thick and
straight stromal nerve trunks extend laterally and anteriorly to give rise to plexiform arrangements of
progressively thin nerve fibers at several levels within the stroma.[13] The nerve fibers perforate
Bowman's layer and eventually form a dense nerve plexus just beneath the basal epithelial cell layer
characterized by tortuous, thin beaded nerve fibers interconnected by numerous nerve elements. The
cornea also contains autonomic sympathetic nerve fibers.

Normal human cornea is avascular. The aqueous humor is the main source of nutrients to the cornea.
Blood supply is by tiny vessels at the outer edge of the cornea as well as components supplied by end
branches of the facial and ophthalmic arteries through the aqueous humor and the tear film.

Tear film
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The minute surface irregularities of the corneal surface epithelium are masked by a smooth and regular
overlying tear film. The tear film is the first layer of the cornea with which light comes into contact. In
produces lubrication and hydration to the ocular surface. It is also a source of oxygen, immunoglobulins,
lysozymes, lactoferrin, and α- and β-defensins. The tear film is traditionally told to be composed of three
distinct layers. The most superficial layer is composed of oily secretions of meibomian glands. Because oil
is less dense than water, the secretions float to the top of the tear film to form a smooth refractive surface.
This oily layer also provides an important barrier against the evaporation of the tear film. The aqueous
middle layer of the tear film lies immediately beneath the oily layer. It is produced from the secretion of
the lacrimal gland which is located in the superior lateral orbit. The aqueous is secreted onto the ocular
surface from ducts in the superior fornix. There are also numerous scattered accessory lacrimal glands
embedded within the conjunctiva stroma which contribute to this aqueous layer. The innermost mucin
layer is produced primarily by the conjunctival goblet cells although the epithelial cells of the cornea and
the conjunctiva also contribute. Current understanding is that all the three layers are in the form of a gel on
the ocular surface. Conjunctival goblet cells seem to be important in performing the functions of debris
removal and immune surveillance.[14]

Ocular surface
Thoft and Friend first suggested that cornea, conjunctiva, lacrimal glands, and lids work as an integrated
unit called ocular surface.[15] The anatomical ocular surface is composed of the mucosa that lines the
globe and palpebral surfaces, the corneoscleral limbus, the corneal epithelium, and the tear film.[16]

Sclera, in contrast to cornea, has collagen fibrils which are more haphazard and random. The bulk of
stroma is mostly acellular, except for outer episcleral layer.

Conjunctiva extends from the limbus to the fornices, forming a fold at the fornices of the eyelid and then
extends back around onto the posterior surface of the eyelids. Plica semilunaris is a crescent-shaped fold of
conjunctiva medially with thickened stroma. The caruncle is located medial to the plica and marks the
most medial aspect of the interpalpebral fissure. The bulbar conjunctiva is fairly loosely adherent to the
underlying anterior Tenon's capsule. On histology, the conjunctiva is composed of a surface layer of
nonkeratinizing stratified squamous epithelium overlying vascular stroma composed of loose connective
tissue. A unique feature of conjunctiva is the presence of goblet cells in stratified squamous epithelium.
These goblet cells are specialized apocrine cells which provide the mucin layer to the tear film.[15] The
specific mucin type secreted by these cells has been identified as MUC5AC.

Eyelids provide mechanical protection for the ocular surface. Constant blinking of the lids renews the tear
film over the surface of the cornea and mechanically removes away superficially adherent foreign bodies
and bacteria. Viewed in cross section, it is composed of five layers. The first layer is the cutaneous
epithelium consisting of stratified squamous epithelium. The epithelium rests on very thin dermis. The
orbicularis oculi muscle is a striated muscle that surrounds the orbital margins. Deep to the orbicularis lies
the orbital septum, a membrane sheet which separates the preseptal space from the posterior orbit.
Underneath the septum lie the retractors of the eyelids. The tarsus has a cartilaginous consistency. It is
composed of dense connective tissue which molds tightly to the curvature of the eye to keep the eyelid
firmly on the surface. Within the tarsus are numerous specialized sebaceous glands called the meibomian
glands opening at the lid margin. Their secretions are the main source of superficial lipid layer of the tear
film. Each eyelash follicle is also associated with sebaceous glands called the glands of Moll. In addition,
there are associated apocrine glands called the glands of Zeis.

Financial support and sponsorship

Nil.

Conflicts of interest
There are no conflicts of interest.

References

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4/29/2019 Anatomy of cornea and ocular surface

1. DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011;37:588–
98. [PubMed: 21333881]

2. Rüfer F, Schröder A, Erb C. White-to-white corneal diameter: Normal values in healthy humans
obtained with the orbscan II topography system. Cornea. 2005;24:259–61. [PubMed: 15778595]

3. Fares U, Otri AM, Al-Aqaba MA, Dua HS. Correlation of central and peripheral corneal thickness in
healthy corneas. Cont Lens Anterior Eye. 2012;35:39–45. [PubMed: 21885326]

4. Feizi S, Jafarinasab MR, Karimian F, Hasanpour H, Masudi A. Central and peripheral corneal thickness
measurement in normal and keratoconic eyes using three corneal pachymeters. J Ophthalmic Vis Res.
2014;9:296–304. [PMCID: PMC4307658] [PubMed: 25667728]

5. Dua HS, Faraj LA, Said DG, Gray T, Lowe J. Human corneal anatomy redefined: A novel pre-
descemet's layer (Dua's layer) Ophthalmology. 2013;120:1778–85. [PubMed: 23714320]

6. Thoft RA, Friend J. The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis
Sci. 1983;24:1442–3. [PubMed: 6618809]

7. Meek KM, Boote C. The organization of collagen in the corneal stroma. Exp Eye Res. 2004;78:503–12.
[PubMed: 15106929]

8. Meek KM, Knupp C. Corneal structure and transparency. Prog Retin Eye Res. 2015;49:1–6.
[PMCID: PMC4655862] [PubMed: 26145225]

9. Boote C, Dennis S, Newton RH, Puri H, Meek KM. Collagen fibrils appear more closely packed in the
prepupillary cornea: Optical and biomechanical implications. Invest Ophthalmol Vis Sci. 2003;44:2941–8.
[PubMed: 12824235]

10. Müller LJ, Pels E, Vrensen GF. The specific architecture of the anterior stroma accounts for
maintenance of corneal curvature. Br J Ophthalmol. 2001;85:437–43. [PMCID: PMC1723934] [PubMed:
11264134]

11. Bourne WM, Nelson LR, Hodge DO. Central corneal endothelial cell changes over a ten-year period.
Invest Ophthalmol Vis Sci. 1997;38:779–82. [PubMed: 9071233]

12. Rio-Cristobal A, Martin R. Corneal assessment technologies: Current status. Surv Ophthalmol.
2014;59:599–614. [PubMed: 25223496]

13. Oliveira-Soto L, Efron N. Morphology of corneal nerves using confocal microscopy. Cornea.
2001;20:374–84. [PubMed: 11333324]

14. Gipson IK. The ocular surface: The challenge to enable and protect vision: The friedenwald lecture.
Invest Ophthalmol Vis Sci. 2007;48:4390. [PMCID: PMC2886589] [PubMed: 17898256]

15. Cher I. Ocular surface concepts: Development and citation. Ocul Surf. 2014;12:10–3. [PubMed:
24439042]

16. Gipson IK. Goblet cells of the conjunctiva: A review of recent findings. Prog Retin Eye Res.
2016;54:49–63. [PMCID: PMC4992623] [PubMed: 27091323]

Figures and Tables

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Figure 1

Picture of cornea showing central and peripheral cornea

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Figure 2

Histopathology of cornea showing corneal epithelium, stroma, and Descemet's membrane

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Table 1
Corneal layers with their functions

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Figure 3

Histopathology of corneal epithelium and Bowman's membrane

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Figure 4

Diagram depicting the junctional complexes of the corneal epithelium

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Figure 5

Endothelial cell layer on the specular microscopy

Articles from Indian Journal of Ophthalmology are provided here courtesy of Wolters Kluwer -- Medknow
Publications

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Chapter 6 195

Conjunctiva

Anatomy and physiology  196

Conjunctival signs  198
Conjunctival diagrams  200
Bacterial conjunctivitis (1)  202
Bacterial conjunctivitis (2)  204
Viral conjunctivitis  206
Chlamydial conjunctivitxis  208
Allergic conjunctivitis (1)  210
Allergic conjunctivitis (2)  212
Cicatricial conjunctivitis (1)  213
Cicatricial conjunctivitis (2)  214
Cicatricial conjunctivitis (3)  216
Cicatricial conjunctivitis (4)  218
Dry eyes: clinical features (1)  220
Dry eyes: clinical features (2)  222
Dry eyes: clinical features (3)  224
Dry eyes: treatment (1)  226
Dry eyes: treatment (2)  228
Ocular neuropathic pain  230
Miscellaneous conjunctivitis and conjunctival degenerations  232
Pigmented conjunctival lesions  234
Non-​pigmented conjunctival lesions (1)  236
Non-​pigmented conjunctival lesions (2)  238

S For additional images relevant to this chapter, please see the online
image bank at oxfordmedicine.com/ophthalmologyc6.
196

196 Chapter 6   Conjunctiva

Anatomy and physiology

The conjunctiva is a mucous membrane that is essential for a healthy eye.
At the histological level, it comprises the epithelium, BM, and stroma. At
the macroscopic clinical level, it is divided into palpebral, forniceal, and
bulbar parts.
Microscopic
Epithelium
This is a 2-​to 5-​layered, non-​keratinized epithelium that may be stratified
squamous (palpebral and limbal) or stratified columnar (bulbar conjunctiva).
The microvilli on the apical surface harbour glycoproteins that form a
hydrophilic glycocalyx layer that helps stabilize the tear film. The epithelial
layer also contains goblet cells (constituting about 10% of epithelial cells).
Epithelial BM
The BM consists mainly of type IV collagen, anchoring fibrils, and hemides-
mosomes linking to the conjunctival epithelial cells.
Stroma
This consists of a superficial lymphoid layer and a deeper fibrous layer.
The superficial layer is attached to the epithelium via the BM and contains
lymphoid tissue. The deeper fibrous layer is attached to the episclera/​
Tenon’s layer and comprises collagenous elastic tissue interspersed with
neurovascular tissue.
Macroscopic
Palpebral
This is firmly adherent to the posterior lamella of the lid; it contains the
crypts of Henle and goblet cells (both secrete mucin).
Forniceal
This is loose and relatively mobile. It contains accessory lacrimal glands of
Krause and Wolfring (secrete aqueous component of tears) and goblet cells.
Bulbar
This is loosely attached to the Tenon’s layer but firmly attached at the lim-
bus. It contains glands of Manz (secrete mucin) and goblet cells.
The tear film
Although conventionally described as a defined trilaminar structure, it is
more complex with an underlying muco-​aqueous gradient, rather than two
discrete layers and an overlying lipid layer (see Fig. 6.1).
Mucin
Mucin is secreted primarily by the goblet cells. Membrane-​bound mucins
abuts the surface epithelium and provides a smooth hydrophilic surface that
stabilizes the aqueous against the otherwise hydrophobic epithelium, and
soluble mucins are found within the aqueous layer.
 

Anatomy and physiology 197

Tear flim components and their origins

Lipid Meibomian glands
Glands of Zeis
Aqueous Lacrimal gland
Muco-aqueous component Glands of Krause
Gradient Glands of Wolfring
Mucin Goblet cells
component Glands of Manz
Crypts of Henle
Epithelium

Fig. 6.1 Tear film components and their origins.

Aqueous layer
The aqueous component (secreted by the lacrimal gland and the accessory
glands) consists primarily of water, but also nutritional elements such as
epidermal growth factor, vitamins, glucose, lactoferrin, lysozyme, immuno-
globulins, and cytokines.
Phospholipid layer
The aqueous layer is supported by a phospholipid layer (secreted primarily
by the MGs) that resists evaporative loss of aqueous and stabilizes the tear
film by increasing surface tension. For further details, see E Blepharitis and
meibomian gland dysfunction (MGD) (1), p. 158.
The American Academy of Ophthalmology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The American Academy of Ophthalmology designates this enduring material for a maximum of 15 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of
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BCSC® volumes are designed to increase the physician’s ophthalmic knowledge through study and review. Users of this activity are encouraged to read the text and then answer the study questions
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Basic and Clinical Science Course

Louis B. Cantor, MD, Indianapolis, Indiana, Senior Secretary for Clinical Education
Christopher J. Rapuano, MD, Philadelphia, Pennsylvania, Secretary for Lifelong Learning and Assessment
George A. Cio , MD, New York, New York, BCSC Course Chair

Section 8

Faculty
Robert W. Weisenthal, MD, Chair, De Witt, New York
Mary K. Daly, MD, Lexington, Massachusetts
Denise de Freitas, MD, São Paulo, Brazil
Robert S. Feder, MD, Chicago, Illinois
Stephen E. Orlin, MD, Philadelphia, Pennsylvania
Elmer Y. Tu, MD, Chicago, Illinois
Woodford S. Van Meter, MD, Lexington, Kentucky
David D. Verdier, MD, Grand Rapids, Michigan
The Academy wishes to acknowledge the Cornea Society for recommending faculty members to the BCSC Section 8 committee.
The Academy also wishes to acknowledge the following committees for review of this edition:
Committee on Aging: Rahul T. Pandit, MD, Houston, Texas
Vision Rehabilitation Committee: John D. Shepherd, MD, Omaha, Nebraska
Practicing Ophthalmologists Advisory Committee for Education: Dasa V. Gangadhar, MD, Primary Reviewer, Wichita, Kansas; Edward K. Isbey III, MD, Chair, Asheville, North Carolina; Alice Bashinsky, MD,
Asheville, North Carolina; David Browning, MD, PhD, Charlotte, North Carolina; Bradley D. Fouraker, MD, Tampa, Florida; Steven J. Grosser, MD, Golden Valley, Minnesota; Stephen R. Klapper, MD,
Carmel, Indiana; James A. Savage, MD, Memphis, Tennessee; Michelle S. Ying, MD, Ladson, South Carolina

European Board of Ophthalmology: Joseph Colin, MD, PhD, EBO Chair, Bordeaux, France; Marie-José Tassignon, MD, PhD, FEBO, EBO Liaison, Antwerp, Belgium; Massimo Busin, MD, Forlì, Italy; Béatrice
Cochener-Lamard, MD, PhD, Brest, France; Sheraz M. Daya, MD, London, England, United Kingdom; Günther Grabner, MD, Salzburg, Austria; Rudy M.M.A. Nuijts, MD, PhD, Maastricht, the Netherlands

Financial Disclosures
Academy sta members who contributed to the development of this product state that within the 12 months prior to their contributions to this CME activity and for the duration of development, they have
had no nancial interest in or other relationship with any entity discussed in this course that produces, markets, resells, or distributes ophthalmic health care goods or services consumed by or used in
patients, or with any competing commercial product or service.
The authors and reviewers state that within the 12 months prior to their contributions to this CME activity and for the duration of development, they have had the following nancial relationships:*
Dr Browning: Aerpio Therapeutics (S), Alcon (S), Alimera Sciences (C), Genentech (S), Novartis Pharmaceuticals (S), Ohr Pharmaceutical (S), P zer (S), Regeneron Pharmaceuticals (S)
Dr Busin: Moria (L, P)
Dr Cochener-Lamard: Alcon (L), Bausch + Lomb (L), Laboratoires Théa (C), Novagali-Santen (C), PhysIOL (L), ReVision Optics, Inc (L)
Dr Colin: Abbott Medical Optics (C), Addition Technology, Inc (C), Alcon (C)
Dr Daya: Bausch + Lomb (C, L), PhysIOL (C), STAAR Surgical (C), Technolas Perfect
Vision GmbH (C, L), Zeiss Acri.Tec (C)
Dr Fouraker: Addition Technology (C, L), Alcon (C, L), KeraVision (C, L), OASIS Medical (C, L)
Dr Grabner: Abbott Medical Optics (C, L, S), AcuFocus Inc (L, S), Polytech (C)
Dr Grosser: Ivantis (O)
Dr Isbey: Alcon (S), Allscripts (C), Bausch + Lomb (S), Med ow (C), Oculos Clinical Research (S)
Dr Nuijts: Alcon (L, S), ASICO (P), Bausch + Lomb (C), SensoMotoric Instruments (C, L)
Dr Savage: Allergan (L)
Dr Tassignon: Morcher GmbH (P)
Dr Tu: Eye Bank Association of America (S), Seattle Genetics (C)
The other authors and reviewers state that within the 12 months prior to their contributions to this CME activity and for the duration of development, they have had no nancial interest in or other
relationship with any entity discussed in this course that produces, markets, resells, or distributes ophthalmic health care goods or services consumed by or used in patients, or with any competing
commercial product or service.
*C = consultant fees, paid advisory boards, or fees for attending a meeting; L = lecture fees (honoraria), travel fees, or reimbursements when speaking at the invitation of a commercial sponsor; O =
equity ownership/stock options of publicly or privately traded rms (excluding mutual funds) with manufacturers of commercial ophthalmic products or commercial ophthalmic services; P = patents
and/or royalties that might be viewed as creating a potential con ict of interest; S = grant support for the past year (all sources) and all sources used for a speci c talk or manuscript with no time
limitation

Recent Past Faculty

Natalie A. Afshari, MD
Charles S. Bouchard, MD
Kathryn A. Colby, MD, PhD
David S. Rootman, MD
In addition, the Academy gratefully acknowledges the contributions of numerous past faculty and advisory committee members who have played an important role in the development of previous editions
of the Basic and Clinical Science Course.

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General Introduction

The Basic and Clinical Science Course (BCSC) is designed to meet the needs of residents and practitioners for a comprehensive yet concise curriculum of the eld of ophthalmology. The BCSC has
developed from its original brief outline format, which relied heavily on outside readings, to a more convenient and educationally useful self-contained text. The Academy updates and revises the course
annually, with the goals of integrating the basic science and clinical practice of ophthalmology and of keeping ophthalmologists current with new developments in the various subspecialties.
The BCSC incorporates the e ort and expertise of more than 90 ophthalmologists, organized into 13 Section faculties, working with Academy editorial sta . In addition, the course continues to bene t
from many lasting contributions made by the faculties of previous editions. Members of the Academy Practicing Ophthalmologists Advisory Committee for Education, Committee on Aging, and Vision
Rehabilitation Committee review every volume before major revisions. Members of the European Board of Ophthalmology, organized into Section faculties, also review each volume before major revisions,
focusing primarily on di erences between American and European ophthalmology practice.

Organization of the Course

The Basic and Clinical Science Course comprises 13 volumes, incorporating fundamental ophthalmic knowledge, subspecialty areas, and special topics:
1 Update on General Medicine
2 Fundamentals and Principles of Ophthalmology
3 Clinical Optics
4 Ophthalmic Pathology and Intraocular Tumors
5 Neuro-Ophthalmology
6 Pediatric Ophthalmology and Strabismus
7 Orbit, Eyelids, and Lacrimal System
8 External Disease and Cornea
9 Intraocular Inflammation and Uveitis
1 Glaucoma
0 Lens and Cataract
1
1 Retina and Vitreous
2 Refractive Surgery
1
3
References
Readers who wish to explore speci c topics in greater detail may consult the references cited within each chapter and listed in the Basic Texts section at the back of the book. These references are intended
to be selective rather than exhaustive, chosen by the BCSC faculty as being important, current, and readily available to residents and practitioners.

Multimedia
This edition of Section 8, External Disease and Cornea, includes videos related to topics covered in the book. The videos were selected by members of the BCSC faculty and are available to readers of the
print and electronic versions of Section 8 (www.aao.org/bcscvideo_section08). They are also available to readers of the eBook through the links within the chapters.

Self-Assessment and CME Credit

Each volume of the BCSC is designed as an independent study activity for ophthalmology residents and practitioners. The learning objectives for this volume are given following the Visual Acuity chart.
The text, illustrations, and references provide the information necessary to achieve the objectives; the study questions allow readers to test their understanding of the material and their mastery of the
objectives. Physicians who wish to claim CME credit for this educational activity may do so by following the instructions given at the end of the book.
This Section of the BCSC has been approved by the American Board of Ophthalmology as a Maintenance of Certi cation Part II self-assessment and CME activity.

Conclusion
The Basic and Clinical Science Course has expanded greatly over the years, with the addition of much new text, numerous illustrations, and video content. Recent editions have sought to place a greater
emphasis on clinical applicability while maintaining a solid foundation in basic science. As with any educational program, it re ects the experience of its authors. As its faculties change and medicine
progresses, new viewpoints emerge on controversial subjects and techniques. Not all alternate approaches can be included in this series; as with any educational endeavor, the learner should seek
additional sources, including Academy Preferred Practice Pattern Guidelines.
The BCSC faculty and sta continually strive to improve the educational usefulness of the course; you, the reader, can contribute to this ongoing process. If you have any suggestions or questions about
the series, please do not hesitate to contact the faculty or the editors.
The authors, editors, and reviewers hope that your study of the BCSC will be of lasting value and that each Section will serve as a practical resource for quality patient care.
 Objectives

Upon completion of BCSC Section 8, External Disease and Cornea, the reader should be able to

describe the anatomy of the external eye and cornea

describe the techniques used for systematic evaluation of the cornea, including tests for assessing corneal topography, tensile strength, and endothelial function

identify the distinctive clinical signs of speci c diseases of the ocular surface

identify the two most common underlying causes of dry eye

identify and di erentiate the corneal dystrophies

select the appropriate management of the corneal dystrophies

recognize common corneal manifestations of systemic disease

outline an approach to the evaluation, diagnosis, and management of immune-related and neoplastic disorders of the external eye and anterior segment

describe the indications for and techniques of surgical procedures used in the management of corneal disease, trauma, and refractive error

discuss common surgical interventions for ocular surface disorders such as pterygium and corneal melts

explain the role of full-thickness and lamellar transplantation in the treatment of corneal disease

 
CHAPTER 1

Structure and Function of the External Eye and Cornea

Highlights

Diseases of the external eye and cornea include a wide range of conditions affecting the eyelids, sclera, and ocular surface (cornea, conjunctiva, and limbus). The external eye has both
anatomical and immunologic defense mechanisms that protect the eye against infection and other ocular conditions.
Current corneal disease classifications and evolving corneal grafting techniques make knowledge of corneal anatomy of the utmost clinical and surgical importance.
The total dioptric power of a normal human eye is 58.60 diopters (D), to which the cornea contributes 74%.

Eyelids

The functions of the eyelid are protection of the eye, distribution of tears, mechanical cleaning of the ocular surface, regulation of light exposure for the eye, and partial production of the tear lm. The
eyelid is composed of skin, subcutaneous connective tissue, brous tissue (tarsus), muscle, and mucous membrane (palpebral conjunctiva). The eyelid skin varies in thickness, from 0.5 mm at the eyelid
margin to 1 mm at the orbital rim. Except for ne vellus hairs, the eyelashes (cilia) are the only hairs of the eyelids and are twice as numerous along the upper eyelid compared with the lower margin.
Eyelashes are replaced every 3–5 months and usually regrow in 2 weeks when cut and within 2 months if epilated. They catch small particles and also work as sensors to stimulate re ex eyelid closure.
Blinking stimulates the lacrimal pump to release tears, which are then spread across the cornea, ushing foreign material. Most individuals blink an average of 10–15 times per minute at rest, 20 times per
minute or more during a conversation, and as few as 5 times per minute when concentrating (eg, reading). Blink frequency has also been shown to change in di erent positions of gaze. The orbicularis
oculi muscle, which is innervated by cranial nerve (CN) VII, closes the upper and lower eyelids (Fig 1-1). The levator palpebrae muscle, innervated by CN III, inserts into the tarsal plate and skin and
elevates the upper eyelid. The Müller muscle, innervated by sympathetic nerves, increases the width of the palpebral ssure.
 Figure 1-1 Cross section of the upper eyelid. (Illustration by Christine Gralapp.)

The epidermis of the eyelids abruptly changes from keratinized to nonkeratinized strati ed squamous epithelium at the mucocutaneous junction of the eyelid margin, along the row of meibomian gland
ori ces. Holocrine sebaceous glands and eccrine sweat glands are present in the eyelid skin. Near the eyelid margin are apocrine sweat glands (the glands of Moll) and numerous modi ed sebaceous glands
(the glands of Zeis).
See BCSC Section 2, Fundamentals and Principles of Ophthalmology, and Section 7, Orbit, Eyelids, and Lacrimal System, for additional discussion of eyelid anatomy.
Argilés M, Cardona G, Pérez-Cabré E, Rodríguez M. Blink rate and incomplete blinks in six di erent controlled hard-copy and electronic reading conditions. Invest Ophthalmol Vis Sci.
2015;56(11):6679–6685.
Lin LK, Goko ski KK. Eyelids and the corneal surface. In: Mannis MJ, Holland EJ, eds. Cornea. Vol 1. 4th ed. Philadelphia: Elsevier; 2017:40–45.

Lacrimal Functional Unit

The lacrimal functional unit (LFU; Fig 1-2) is a highly complex apparatus comprising the lacrimal glands, ocular surface, and eyelids, as well as the sensory and motor nerves that connect these
components. The LFU is responsible for the regulation, production, and health of the tear lm. The LFU responds to environmental, endocrinologic, and cortical in uences. Its overall functions are to
preserve the following:

integrity of the tear film (by carrying out lubricating, antimicrobial, and nutritional roles)
health of the ocular surface (by maintaining corneal transparency and the surface stem cell population)
the quality of the image projected onto the retina
 Figure 1-2 The sensory and motor nerves connecting the components of the lacrimal functional unit. CN = cranial nerve. (Modi ed with permission from P ugfelder SC, Beuerman RW, Stern ME, eds. Dry
Eye and Ocular Surface Disorders. New York: Marcel Dekker; 2004.)

The a erent component of the LFU is mediated through ocular surface and trigeminal nociceptors, which synapse in the brainstem with autonomic and motor (e erent) nerves. The autonomic nerve
bers innervate the meibomian glands, conjunctival goblet cells, and lacrimal glands. The motor nerve bers innervate the orbicularis muscle to initiate blinking. During blinking, the meibomian glands
express lipid, and the tears are replenished from the inferior tear meniscus and spread across the cornea while excess tears are directed into the lacrimal puncta.

P ugfelder SC, Beuerman RW, Stern ME, eds. Dry Eye and Ocular Surface Disorders. Boca Raton, FL: CRC Press/Taylor & Francis; 2004.

Tear Film

Our understanding of the structure and composition of the tear lm has gradually evolved. The tear lm was formerly described as a structure composed of 3 layers: lipid (expressed from the meibomian
glands), aqueous (expressed from the lacrimal gland), and mucin (produced primarily by goblet cells). It is now thought of as a uniform gel consisting of soluble mucus, which is secreted by conjunctival
goblet cells, mixed with uids and proteins secreted by the lacrimal glands (Fig 1-3).
 Figure 1-3 Components of the tear lm—produced by the lacrimal glands, conjunctival goblet cells, and surface epithelium—lubricate (mucins), heal (epidermal growth factor [EGF]), and protect the
cornea from infection (lactoferrin, defensins, immunoglobulin A [IgA]). When the tear lm is in amed, it produces interleukin‑1 receptor antagonist (IL‑1RA), transforming growth factor β (TGF‑β), and
tissue inhibitor of matrix metalloproteinase 1 (TIMP 1). MMP‑9 = matrix metalloproteinase 9. (Modi ed with permission from P ugfelder SC. Tear dysfunction and the cornea: LXVIII Edward Jackson
Memorial Lecture. Am J Ophthalmol. 2011;152(6):902.)

The air–tear lm interface at the surface of the cornea constitutes the primary refractive element of the eye. The tear lm is primarily responsible for maintaining a smooth optical surface between
blinks. It also serves as a medium to remove irritants and pathogens and contains a variety of elements that control the normal ocular ora. Further, tears dilute toxins and allergens and allow for the
di usion of oxygen and other nutrients. Maintenance of the tear lm is thus critical to normal corneal function.
P ugfelder SC. Tear dysfunction and the cornea: LXVIII Edward Jackson Memorial Lecture. Am J Ophthalmol. 2011;152(6):900–909.

Conjunctiva

The conjunctiva can be broadly divided as follows: bulbar (covers the eyeball), forniceal (covers the superior and inferior fornices), and palpebral, or tarsal (starts at the mucocutaneous junction of the
eyelid and covers the inner eyelid). The caruncle—a eshy, ovoid modi ed mass approximately 5 mm high and 3 mm wide, containing the lacus lacrimalis—is attached to the inferomedial side of the plica
semilunaris and bears goblet cells and lacrimal tissue, as well as hairs, sebaceous glands, and sweat glands. The plica semilunaris is a crescent-shaped vertical fold at the medial angle of the eye. The
palpebral, or tarsal, conjunctiva is tightly adherent to the underlying tarsus. The bulbar conjunctiva is loosely attached to the Tenon capsule, and both insert into the limbus.
The cell morphology of the conjunctival epithelium varies from strati ed cuboidal over the tarsus and columnar in the fornices to squamous on the globe. Goblet cells account for up to 10% of basal
cells of the conjunctival epithelium and are most numerous in the tarsal conjunctiva, the inferonasal bulbar conjunctiva, and in the area of the plica semilunaris.
The substantia propria of the conjunctiva consists of loose connective tissue. Conjunctiva-associated lymphoid tissue (CALT), which consists of lymphocytes and other leukocytes, is present, especially in
the fornices. Lymphocytes interact with mucosal epithelial cells through reciprocal regulatory signals mediated by growth factors, cytokines, and neuropeptides.
The palpebral conjunctiva shares its blood supply with the eyelids. The bulbar conjunctiva is supplied by the anterior ciliary arteries, which arise from muscular branches of the ophthalmic artery. These
capillaries are fenestrated and leak uid, producing chemosis (conjunctival swelling), as a response to allergies or other in ammatory events.

Cornea

The cornea is a transparent, avascular tissue that consists of 5 layers (Fig 1-4): epithelium, Bowman, stroma, Descemet membrane, and endothelium; these are discussed in the following subsections.
 Figure 1-4 The layers of the normal cornea. The epithelium is composed of 4–6 cell layers, but it can increase in thickness to maintain a smooth surface (hematoxylin-eosin, ×32).

In adults, the cornea measures 11–12 mm horizontally and 10–11 mm vertically. It is approximately 500–600 μm thick at its center and gradually increases in thickness toward the periphery. The
cornea is aspheric, although the central portion of the anterior corneal surface is often described as a spherocylindrical convex mirror. The general refractive index of the cornea is 1.376. The average
radius of curvature of the anterior central cornea is 7.8 mm, which would produce a dioptric power of 43.25 D for the front surface of the cornea, using the keratometer calibration index of 1.3375. The
total dioptric power of a normal human eye is 58.60 D, to which the cornea contributes 74%. The cornea is also the major source of astigmatism in the human optical system. For further discussion of
corneal optics, see Evaluation of Corneal Curvature in Chapter 2.
For its nutrition, the cornea depends on di usion of glucose from the aqueous humor and of oxygen through the tear lm. In addition, the peripheral cornea is supplied with oxygen from the limbal
circulation.
The density of nerve endings in the cornea is among the highest in the body, and the sensitivity of the cornea is 100 times that of the conjunctiva. Sensory nerve bers extend from the long ciliary
nerves and form a subepithelial plexus.

Corneal Epithelium
The corneal epithelium is composed of 4–6 layers, which include 1–2 layers of super cial squamous cells, 2–3 layers of broad wing cells, and an innermost layer of columnar basal cells. It is 40–50 μm
thick (see Fig 1-4; also see the Pachymetry section in Chapter 2). The epithelium and tear lm form an optically smooth surface. Tight junctions between super cial epithelial cells prevent penetration of
tear uid into the stroma. Continuous proliferation of limbal stem cells gives rise to the other layers, which subsequently di erentiate into super cial cells. With maturation, these di erentiated cells
become coated with microvilli on their outermost surface and then desquamate into the tears. The process of di erentiation takes approximately 7–14 days. Basal epithelial cells secrete a continuous, 50-
nm-thick basement membrane, which is composed of type IV collagen, laminin, and other proteins. Corneal clarity depends on the tight packing of epithelial cells, which results in a layer with a nearly
uniform refractive index and minimal light scattering.

Bowman Layer
The Bowman layer lies anterior to the corneal stroma. Previously considered a membrane, the Bowman layer is rather the acellular condensate of the most anterior portion of the stroma (see Fig 1-4). This
layer is 15 μm thick and helps maintain the shape of the cornea. When disrupted, it will not regenerate.

Corneal Stroma
The corneal stroma makes up roughly 90% of the total corneal thickness (see Fig 1-4). The regular arrangement of stromal cells (keratocytes), bers, and extracellular matrix is necessary for a clear cornea.
Keratocytes vary in size and density throughout the stroma and form a 3-dimensional network throughout the cornea. They are attened broblasts, located between the stromal collagen lamellae (Fig 1-
5), and they continually digest and manufacture stromal molecules. Keratocyte density declines with age, by 0.9% per year for anterior density and by 0.3% per year for posterior density. It can also
decline with refractive laser surgery and may not be completely restored.
 Figure 1-5 Keratocytes (A) are attened broblasts (B) situated between the stromal collagen lamellae. (Reproduced with permission from Oyster CW. The Human Eye: Structure and Function. Sunderland,
MA: Sinauer Associates; 1999:331.)

The corneal stroma is composed of an extracellular matrix formed of collagens and proteoglycans. Type I and type V brillar collagens are intertwined with laments of type VI collagen. The major
corneal proteoglycans are decorin (associated with dermatan sulfate) and lumican (associated with keratan sulfate).
Corneal transparency depends on maintaining the water content of the corneal stroma at 78%. Corneal hydration is largely controlled by intact epithelial and endothelial barriers and the functioning of
the endothelial pump, which is linked to an ion-transport system controlled by temperature-dependent enzymes such as Na+,K+-ATPase. In addition, negatively charged stromal glycosaminoglycans tend
to repel each other, producing a swelling pressure (SP). Because the intraocular pressure (IOP) tends to compress the cornea, the overall imbibition pressure of the corneal stroma is given as IOP – SP. The
total transendothelial osmotic force is calculated by adding the imbibition pressure and the various electrolyte gradients produced by the endothelial transport channels. Corneal hydration varies from
anterior to posterior and increases closer to the endothelium.
Schlötzer-Schrehardt U, Bachmann BO, Tourtas T, et al. Ultrastructure of the posterior corneal stroma. Ophthalmology. 2015;122(4):693–699.

Descemet Membrane
The Descemet membrane is the basement membrane of the corneal endothelium (see Fig 1-4). It is 3 μm at birth and increases in size, to 10–12 μm in adulthood, as the endothelium gradually lays down a
posterior amorphous, nonbanded zone. Though controversial, a novel layer in the posterior part of the cornea (pre-Descemet layer or Dua’s layer) has been reported. This layer may be important during
deep anterior lamellar keratoplasty. The Schwalbe line is a gonioscopic landmark that de nes the end of the Descemet membrane and the beginning of the trabecular meshwork.
Dua HS, Faraj LA, Said DG, Gray T, Lowe J. Human corneal anatomy rede ned: a novel pre-Descemet’s layer (Dua’s layer). Ophthalmology. 2013;120(9):1778–1785.

Corneal Endothelium
Corneal endothelial cells lie on the posterior surface of the cornea, composing a monolayer of closely interdigitated cells arranged in a mosaic pattern of mostly hexagonal shapes (see Fig 1-4). Human
endothelial cells do not proliferate in vivo, but they can divide in cell culture. If cell loss occurs, especially as a result of trauma or surgery, the defective area is covered via enlargement and spread of
residual cells or perhaps peripheral stem cells. These cell ndings can be observed by specular microscopy as polymegethism (variability in cell size) and polymorphism (variability in cell shape). Cell
density varies over the endothelial surface; normally, the concentration is highest in the periphery. Central endothelial cell density decreases with age at an average rate of approximately 0.6%/year,
diminishing from a count of about 3400 cells/mm2 at age 15 years to about 2300 cells/mm2 at age 85 years. The normal central endothelial cell count is between 2000 and 3000 cells/mm2. It has been
observed that eyes with an endothelial cell count below 500 cells/mm2 may be at risk for development of corneal edema. The endothelium maintains corneal transparency by controlling corneal hydration
and maintaining stromal deturgescence through its functions as a barrier to the aqueous humor and as a metabolic pump that moves ions, and draws water osmotically, from the stroma into the aqueous
humor. The barrier and pump functions of the endothelium can be measured clinically by uorophotometry and pachymetry. The endothelium must also be permeable to nutrients and other molecules
from the aqueous humor. Increased permeability and insu cient pump sites occur with reduced endothelial cell density, although the cell density at which clinically evident edema occurs is not an
absolute.
For more detailed information on the histology and physiology of the cornea, see BCSC Section 2, Fundamentals and Principles of Ophthalmology, Chapter 8.
Bourne WM. Biology of the corneal endothelium in health and disease. Eye (Lond). 2003; 17(8):912–918.
DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011; 37(3):588–598.
Gambato C, Longhin E, Catania AG, Lazzarini D, Parrozzani R, Midena E. Aging and corneal layers: an in vivo corneal confocal microscopy study. Graefes Arch Clin Exp Ophthalmol.
2015;253(2):267–275.
Nishida T, Saika S, Morishige N. Cornea and sclera: anatomy and physiology. In: Mannis MJ, Holland EJ, eds. Cornea. Vol 1. 4th ed. Philadelphia: Elsevier; 2017:1–22.
Whikehart DR, Parikh CH, Vaughn AV, Mishler K, Edelhauser HF. Evidence suggesting the existence of stem cells for the human corneal endothelium. Mol Vis. 2005;11:816–824.

Limbus

The limbus is the transition zone between transparent cornea and opaque sclera. This area harbors corneal epithelial stem cells, which are responsible for the normal homeostasis and wound repair of the
corneal epithelium. The palisades of Vogt, which are concentrated in the superior and inferior limbus, are thought to be the site of the limbal stem cells’ niche and can be observed biomicroscopically as
radially oriented brovascular ridges concentrated along the corneoscleral limbus (Fig 1-6). The posterior limbus appears to be responsible for stem cell maintenance, while the function of the anterior
limbus may be to prompt regeneration of corneal epithelium. Renewal occurs from basal cells, with centripetal migration of stem cells from the periphery. This is known as the XYZ hypothesis, where X
represents proliferation and strati cation of limbal basal cells; Y, centripetal migration of basal cells; and Z, desquamation of super cial cells. The health of the cornea depends on the sum of X and Y being
equal to Z. Damage to epithelial stem cells impairs long-term regeneration of corneal epithelial cells. Damage to the limbus leads to loss of the barrier that prevents invasion of the conjunctiva and
neovascularization of the ocular surface.
 Figure 1-6 Slit‑lamp photograph showing the corneoscleral limbus with radially oriented brovascular ridges (palisades of Vogt). (Courtesy of Cornea Service, Paulista School of Medicine, Federal University
of São Paulo.)

Singh V, Shukla S, Ramachandran C, et al. Science and art of cell-based ocular surface regeneration. Int Rev Cell Mol Biol. 2015;319:45–106.
Yoon JJ, Ismail S, Sherwin T. Limbal stem cells: central concepts of corneal epithelial homeostasis. World J Stem Cells. 2014;6(4):391–403.

Defense Mechanisms of the External Eye and Cornea

The external eye and cornea comprise complexly integrated tissues that, along with the tear lm, help protect the eye against infection. For an in-depth discussion of the various features of the innate and
adaptive arms of the immune system, see BCSC Section 9, Intraocular In ammation and Uveitis. BCSC Section 2, Fundamentals and Principles of Ophthalmology, discusses the biochemistry, metabolism, and
immunology of the tear lm and cornea in detail.
Components of the ocular adnexa—periorbital area, eyelids and lashes, lacrimal and meibomian glands—play di erent but important roles in the production, spread, and drainage of the tear lm. As
discussed earlier, the tear lm serves as a protective layer, washing away irritants and pathogens and diluting toxins and allergens. Each functional blink promotes tear turnover. Tears are secreted from
the lacrimal gland and spread across the cornea while excess tears are directed into the lacrimal puncta; all of these actions reduce the contact time of microbes and irritants with the ocular surface.
Immunoregulation of the ocular surface occurs through tolerance and regulation of the innate and adaptive arms of the ocular immune response (Fig 1-7). The normal tear lm contains components of
the complement cascade, proteins, growth factors, and an array of cytokines. Cytokines such as interleukin-1 and tumor necrosis factor α are signi cantly upregulated in a variety of corneal in ammatory
diseases, such as corneal graft rejection and dry eye disease. Similarly, increased expression of growth factors, prostaglandins, neuropeptides, and proteases has been observed in a wide array of immune
disorders of the ocular surface.
 Figure 1-7 Immunoregulation of the ocular surface. A, Immunoregulation of the ocular surface: The ocular surface tissues contain a variety of soluble and cellular factors to reduce in ammation-
induced pathology in the lacrimal functional unit. Those implicated in immunoregulation within the ocular surface tissues include the following: (1) Natural regulatory T cells (nTreg cells) (eg, CD4+,
CD8+, and natural killer T cells), which include many of the conjunctival intraepithelial lymphocytes, are thought to dampen or inhibit the in ammatory/autoimmune response on the ocular surface.
(2) The anti-in ammatory cytokine transforming growth factor β (TGF‑β) is present on the ocular surface and has profound suppressive e ects on resident dendritic cell (DC) maturation in the cornea;
proliferation, di erentiation, and survival of autoreactive T cells; and Treg cell di erentiation and maintenance. The activity of the potent acute-response, proin ammatory cytokine interleukin‑1 (IL‑1)
is modulated by the IL‑1 receptor antagonist (IL‑1RA), which is expressed and secreted by corneal and conjunctival epithelial cells. Vasoactive intestinal peptide (VIP) also seems to be protective; VIP
secreted by sensory nerve endings in the cornea increases production of TGF‑β and IL‑10 and inhibits expression of the proin ammatory cytokines and chemokines, IL‑1β, tumor necrosis factor α,
interferon‑γ, and chemokine (C‑X‑C motif) ligand 2. Hormones are also implicated in curbing in ammation and maintaining homeostasis. In addition, the corneal epithelium expresses vascular
endothelial growth factor (VEGF) receptor‑1 to sequester VEGF and reduce neovascularization. (3) Antigen-presenting cells (APCs) bearing self-antigen derived at the ocular surface may migrate to the
regional lymph nodes to induce antigen-speci c Treg cells (iTreg cells). B, Immunoregulation in the lymphoid organs: nTreg cells may exert their immunosuppressive function through (1) release of
soluble factors (eg, TGF‑β, IL‑10); (2) cell–cell contact, which disables pathogenic e ector T cells (Te cells) and/or APCs; and/or (3) competition for soluble factors (eg, IL‑2). (4) iTreg cells may use
similar mechanisms to inhibit cells bearing or responding to autoantigens. It is possible that these Treg-dependent mechanisms may also function within the ocular surface tissues. C, Other peripheral
immunoregulatory mechanisms: additional mechanisms also limit access and e ector function of autoreactive T cells within the ocular surface tissues: (1) TGF‑β and (2) nTreg and iTreg cells are
thought to suppress in ltrating autoreactive lymphocytes, and (3) low‑level expression of integrins in endothelial cells of the healthy ocular surface, coupled with expression of the programmed death
ligand‑1 (PD‑L1), negatively regulates activated T cells within the ocular surface tissues. (Modi ed with permission from Stern ME, Schaumburg CS, Dana R, Calonge M, Niederkorn JY, P ugfelder SC.
Autoimmunity at the ocular surface: pathogenesis and regulation. Mucosal Immunol. 2010;3(5):425–442.)

The normal, unin amed conjunctiva contains polymorphonuclear leukocytes (neutrophils), lymphocytes (including regulatory T cells [Treg cells], which dampen the immune response), macrophages,
plasma cells, and mast cells. The conjunctival stroma has an endowment of dendritic antigen-presenting cells (APCs). The conjunctival epithelium contains a special subpopulation of dendritic APCs known
as Langerhans cells, which are capable of both uptake of antigens and priming (sensitizing) of naive (antigen-inexperienced) T lymphocytes. Hence, these dendritic cells serve as the sentinel cells of the
immune system of the ocular surface. In addition to containing immune cells, the conjunctiva has a plentiful supply of blood vessels and lymphatic vessels, which facilitate the tra cking of immune cells
and antigens to the draining lymph nodes, where the adaptive immune response is generated. This occurs through the recruitment of Treg cells, which return to the ocular surface to modulate and suppress
the local immune response.
The normal, unin amed cornea, like the conjunctiva, is also endowed with dendritic cells. Like those in the conjunctiva, the dendritic APCs in the corneal epithelium are Langerhans cells. They are
located primarily in the corneal periphery and limbus (Fig 1-8). These APCs are in an activated, mature state (expressing class II major histocompatibility complex [MHC] antigens and costimulatory
molecules) and hence are capable of e ciently stimulating T cells. In addition to these dendritic cells, small numbers of lymphocytes are present in the peripheral epithelium and anterior stroma of the
cornea. A highly regulated process, mediated by vascular endothelial adhesion molecules and cytokines, controls the recruitment of the various leukocyte subsets from the intravascular compartment into
the limbal matrix. Immune responses are also mediated by Treg cells in the regional lymph nodes and perhaps at the local level as well. See also Chapter 11 on corneal graft rejection.

Figure 1-8 Langerhans cells. This micrograph shows the predominance of major histocompatibility complex class II+ Langerhans cells in the limbus of the unin amed eye. (Courtesy of the laboratory of
M. Reza Dana, MD.)

Ecoi er T, Yuen D, Chen L. Di erential distribution of blood and lymphatic vessels in the murine cornea. Invest Ophthalmol Vis Sci. 2010;51(5):2436–2440.
Niederkorn JY. Cornea: window to ocular immunology. Curr Immunol Rev. 2011;7(3): 328–335.
Stern ME, Schaumburg CS, Dana R, Calonge M, Niederkorn JY, P ugfelder SC. Autoimmunity at the ocular surface: pathogenesis and regulation. Mucosal Immunol. 2010; 3(5):425–442.
CHAPTER 2

Examination Techniques for the External Eye and Cornea

Highlights

Placement of a hard contact lens on an irregular cornea provides a smooth anterior surface, helping the clinician to determine the contribution of the surface irregularity to vision loss.
Evaluation of the mires projected onto the cornea during keratometry and Placido disk–based topography can help distinguish irregular astigmatism (distorted mires) due to ocular
surface irregularity from regular corneal astigmatism (clear but oval mires).
Corneal topography and tomography can give the clinician accurate data on corneal power, elevation, and thickness that are useful in diagnosis and surgical planning.

Direct Visualization

Slit-Lamp Biomicroscopy
The slit lamp is a fundamental and invaluable tool in the ophthalmologist’s armamentarium. Mastery of the slit-lamp examination is critical in categorizing corneal pathology and formulating a diagnostic
(Fig 2-1) and therapeutic plan.
 Malaysian Family Physician 2008; Volume 3, Number 2
ISSN: 1985-207X (print), 1985-2274 (electronic)
©Academy of Family Physicians of Malaysia
Online version: http://www.ejournal.afpm.org.my/

Review Article
NEONATAL CONJUNCTIVITIS – A REVIEW

PS Mallika1, MS; T Asok2, MMed; Faisal HA2, MS; S Aziz2, MS; AK Tan1, MD; G Intan2, MS.

1Department of Ophthalmology, Faculty of Medicine and Health Sciences, University Malaysia Sarawak, Kuching, Sarawak,
Malaysia (Mallika Premsenthil)
2Department of Ophthalmology, Sarawak General Hospital, Kuching, Sarawak, Malaysia (Asokumaran Thanaraj, Humayun Akter

Faisal, Mohamad Aziz Salowi, Tan Aik Kah, Intan Gudom)

Address for correspondence: Dr. Mallika Premsenthil, Lecturer, Ophthalmology unit, Faculty of Medicine and Health Sciences, University
Malaysia Sarawak, Lot 77, Sekysen 22 Kuching Town Land District, Jalan Tun Ahmad Zaidi Adruce, 93150 Kuching, Sarawak, Malaysia. Tel:
+6082-416550, Fax: + 6082-422564, Email: pmallika@fmhs.unimas.my

Conflict of interest: None

ABSTRACT
Ophthalmia neonatorum remains a significant cause of ocular morbidity, blindness and even death in underdeveloped countries. The
organisms causing ophthalmia neonatorum are acquired mainly from the mother’s birth canal during delivery and a small percentage of
cases are acquired by other ways. Chlamydia and Neisseria are the most common pathogens responsible for the perinatal infection.
Fortunately in most cases, laboratory studies can identify the causative organism and unlike other form of conjunctivitis, this perinatal
ocular infection has to be treated with systemic antibiotics to prevent systemic colonization of the organism. Routine prophylaxis with 1%
silver nitrate solution (crédés method) has been discontinued in many developed nations for the fear of development of chemical conjunctivitis.
Key words: Crédés Prophylaxis; Neonatal Conjunctivitis; Ophthalmia Neonatorum; Sexually Transmitted Diseases.
Mallika PS, Asok T, Aziz S, Faisal HA, Tan AK, Intan G. Neonatal conjunctivitis – a review. Malaysian Family Physician. 2008;3(2):77-81

INTRODUCTION trachomatis and Neisseria gonorrhoea.7 Apart from bacteria,

Neonatal conjunctivitis is often known as ophthalmia
neonatorum (Latin name). It is defined as conjunctivitis
occurring in a newborn during the first month of life with clinical
signs of erythema and oedema of the eyelids and the palpebral
conjunctivae, purulent eye discharge with one or more
polymorph nuclear per oil immersion field on a Gram stained
conjunctival smear.1 Originally described in 1750, it is one of
the most common infections occurring in the first month of
life.2
Ophthalmia neonatorum leads to blindness in approximately
10,000 babies annually worldwide.3 The major causes of
Ophthalmia neonatorum are, in decreasing order, chemical
inflammation, bacterial infection and viral infection. The
majority of infectious neonatal conjunctivitis are due to
bacteria.4 The bacterial causes include sexually transmitted
diseases agents (Chlamydia trachomatis and Neisseria
gonorrhoea), microorganisms from the skin (Staphylococcus
aureus) and the mother’s gastrointestinal tract (Pseudomonas
sp).5 The inflammation usually resolves spontaneously within
a few days. Therefore, simple Gram stain and routine bacterial
culture are often the only investigations that are required in
most cases. 6 Although simple investigation suffices, treatment
has to be adequate because systemic complication and severe
visual loss can occur in infection particularly with Chlamydia
herpes viruses can also cause neonatal conjunctivitis.
The organisms causing neonatal conjunctivitis are usually
acquired from the infected birth canal of the mother, though
some may acquire the infection from their immediate
surroundings.8 The predisposing factors, which can increase
the chance of the newborn acquiring neonatal conjunctivitis,
include increase shedding of these organisms in the vaginal
tract of the mother during the last trimester, premature rupture
of membranes and prolonged labor. Neonatal conjunctivitis
following caesarean section could be due to intrauterine
chlamydial infection as the result of early rupture of the
membranes8 or trans-placental or transmembrane transfer of
these organisms.9
The epidemiology of Ophthalmia Neonatorum has changed
following the prophylactic use of 1% silver nitrate solution
(Crédé method); there was a marked reduction in the incidence
of ophthalmia in the United States, Europe, and the United
Kingdom following the widespread application of the Crédé
prophylaxis.10 However, the role of silver nitrate prophylaxis
is only to prevent ophthalmia due to gonococcal infections; it
is not effective against Chlamydia. Silver nitrate prophylaxis
is not used currently due to the ineffectiveness in preventing
chlamydial infection and the tendency to cause chemical
conjunctivitis. This method of prophylaxis has been replaced
by the use of erythromycin or tetracycline ointment.11

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 Malaysian Family Physician 2008; Volume 3, Number 2
ISSN: 1985-207X (print), 1985-2274 (electronic)
©Academy of Family Physicians of Malaysia
Online version: http://www.ejournal.afpm.org.my/
EPIDEMIOLOGY
Ophthalmia neonatorum is a worldwide problem. The
pathogens responsible for causing the infection vary
geographically due to the differences in the prevalence of
maternal infection and the prophylactic use of antibiotics and
silver nitrate solution.2 In the developed world, Chlamydia has
been reported as the most common infectious agent
responsible for ophthalmia compared to gonococcus. However
in developing nations, both chlamydial and gonococcal
infections are prevalent. In Malaysia the incidence is
significantly high due to lack of routine prophylactic measures
and due to emergence of pencillinase-producing N.
gonorrhoea (PPNG) strains. The actual incidence is unknown
due to under-reporting. A study on gonococcal ophthalmia
neonatorum in the state of Kelantan has shown an increase
in the percentage of cases infected with penicillin resistant
strains of N. gonorrhoea from 6.4% to 25.9%.12 Lockie P et al
13 in their retrospective study involving 80 cases reported 7.5%
due to PPNG. The Pencillinase-producing strains are believed
to originate from South-East Asian region namely from
Bangkok where 48.9% of strains of N. gonorrhoea isolated
were due to PPNG.14
The prevalence of ophthalmia due to gonococcal infection is
reported to be 0.04 per 1000 live births in Belgium and
Netherlands, and 0.3 per 1000 live births in the United
States.15,16 At the moment, Chlamydia trachomatis is the most
frequent sexually transmitted pathogen in the developed
nations with prevalence of 5 to 60 per 1000 live births in the
United States, 4 per1000 live births in the United Kingdom
and 40 per 100 live births in Belgium; whereas the prevalence
of gonorrhoea among antenatal attenders in the African
countries ranges from 4% to 15 %.17 Approximately 25% to
50% of infants exposed to Chlamydia trachomatis and
Neisseria gonorrhoea develop neonatal conjunctivitis, without
prophylaxis.18
ETIOLOGY
Ophthalmia neonatorum can be divided into aseptic and septic
types.10 The aseptic type (chemical conjunctivitis) is generally
secondary to the instillation of silver nitrate drops for ocular
prophylaxis. Septic neonatal conjunctivitis is mainly caused
by bacterial and viral infections. Chlamydia trachomatis and
Neisseria gonorrhoea the two sexually transmitted agents are
associated with systemic complications and severe visual loss
if left untreated.19,20
Chlamydia trachomatis is the most common cause of
ophthalmia neonatorum in the developed countries because
of higher prevalence of Chlamydia as sexually transmitted
disease. This is due to the fact that 60% to 80% of genital
78
AFPM J Vol 3 No 2.pmd 78
infections with Chlamydia in females are asymptomatic. Hence
it is often labeled as “silent epidemic”.21 The Center for Disease
Prevention and Control (CDC) estimates 3 million cases of
chlamydial infections occur per year. It is more prevalent than
gonococcal infection and approximately four to six times as
common as herpes virus infection.22
Although gonococcus is the second commonest organism
responsible for ophthalmia neonatorum, it is the most virulent
infectious agent for neonatal conjunctivitis. It was previously
the commonest cause of blindness within the first year of life,
necessitating the use of prophylaxis at birth. Gonococcal
ophthalmia neonatorum had been eradicated in the United
States in the 1950’s. However, it has now resurfaced following
the increasing incidence of adult gonococcal infections and
the development of antimicrobial resistance.23
The other microbial causes of ophthalmia include
Staphylococcus aureus, Streptococcus pneumoniae,
Haemophilus influenzae, Escherichia coli, Klebsiella sp and
Pseudomonas aeruginosa.24,25
CLINICAL FEATURES
The genital serovars type D-K of Chlamydia trachomatis
causes neonatal conjunctivitis. It has a later onset than
gonococcal conjunctivitis. The incubation period is 5-14 days
and the colonization of the eye after birth does not always
result in infection. Almost 40% of the infected neonates develop
watery conjunctivitis which becomes more copious and
purulent later. Most of the cases are mild and self-limited, but
occasionally may be severe with eyelid swelling, chemosis,
papillary reaction, pseudo-membrane, peripheral pannus and
corneal involvement. If left untreated, 10-20% of the cases
will develop infantile pneumonia. Other extra ocular
involvement of Chlamydia includes nasopharyngeal, rectal and
vaginal colonization and other form of diseases such as infant
pneumonia syndrome.26
Gonococcal conjunctivitis is more severe than chlamydial
conjunctivitis. The incubation period is 2-5 days. However, it
can occur earlier in cases of premature rupture of membranes.
It is usually bilateral. The conjunctivitis is characterized by
severe hyper-acute purulent discharge, eyelid edema and
chemosis. Gonococci have the capacity to penetrate intact
corneal epithelium, leading to corneal epithelial edema and
corneal ulceration, which can progress to corneal perforation
and endophthalmitis if unrecognized. Hence in all cases of
neonatal conjunctivitis, the infant has to be screened for
gonococci to prevent these serious consequences.
Gonococcal infection of the newborn can also give rise to
systemic complications like stomatitis, arthritis, rhinitis,
septicemia and meningitis.27
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 Malaysian Family Physician 2008; Volume 3, Number 2
ISSN: 1985-207X (print), 1985-2274 (electronic)
©Academy of Family Physicians of Malaysia
Online version: http://www.ejournal.afpm.org.my/
Herpes simplex keratoconjunctivitis in an infant usually
presents with generalized herpes infection. Vesicles around
the eye and corneal involvement are also common.28 Chemical
conjunctivitis usually occurs within 24 hours of instillation of
silver nitrate solution and resolves spontaneously within a few
days. It can present with lid swelling associated with redness
of the eyes, rarely with lacrimal stenosis. Ophthalmia
Neonatorum due to other microbial causes usually run a milder
course without corneal and systemic involvement.
LABORATORY DIAGNOSIS
Ophthalmia neonatorum is essentially a clinical diagnosis
made by observation of signs and symptoms. The clinical
differentiation between various types of neonatal conjunctivitis
can be difficult.29,30 Hence lab diagnosis is of paramount
importance in establishing the correct diagnosis and initiating
the best treatment. Conjunctival scrapings for Gram stain and
Giemsa stain should be obtained from the palpebral
conjunctiva of all the infants with neonatal conjunctivitis. The
presence of intracellular gram negative diplococci (IGND) has
a high sensitivity and specificity and predictive value.31 Blood
agar, chocolate agar and/or Thayer-Martin media can be used
to isolate Neisseria gonorrhoea and other bacteria.
Chlamydia trachomatis can be isolated by the presence of
intracytoplasmic inclusion bodies in the Giemsa stain in 60-
80% of all infants. Conjunctival swab, smeared on to a
microscopic slide and stained with Chlamydia trachomatis
specific fluorescent monoclonal antibody (direct
immunofluorescence test) often shows the presence of an
impressively large number of punctate, fluorescing chlamydial
elementary bodies, resembling “star-spangled sky at night”.32
This antigen detection test is still considered the “gold standard”
for the diagnosis of chlamydial infections.33 Polymerase chain
reaction (PCR) analysis for diagnosing chlamydial
conjunctivitis has an advantage of early diagnosis and higher
specificity compared to McCoy cell culture. 34 The other
laboratory studies for diagnosing chlamydial infections include
Micro immunofluorescence assay (MIF) for detection of
Chlamydia trachomatis IgG and IgM antibodies and Elisa tests.
PROPHYLAXIS
Crédé introduced 2% silver nitrate as a prophylaxis treatment
method for conjunctivitis in the newborns in Leipzig in 1881.35
The widespread use of silver nitrate prophylaxis was
associated with a drastic decline in the incidence of
gonococcal ophthalmia throughout Europe and the United
States. However, silver nitrate is toxic and for many years has
been recognised to be a common cause of chemical
conjunctivitis.36 Currently, topical erythromycin and tetracycline
are also used as alternatives for ocular prophylaxis.11 However,
AFPM J Vol 3 No 2.pmd 79
all these agents are considered effective only for gonococcal
ophthalmia, and found to be ineffective as prophylactic
treatment against chlamydial conjunctivitis.37 Bell et al38 found
no significant difference in the efficacy of silver nitrate, topical
erythromycin and no prophylaxis in preventing ophthalmia
neonatorum. Instead of prophylaxis, the authors concluded
that prenatal recognition and prompt treatment may prevent
the development of the disease.
TREATMENT
Ophthalmia neonatorum is an ocular emergency so all infants
with neonatal conjunctivitis should be admitted. Specific
treatment modalities are available for different types of
neonatal conjunctivitis and treatment should be based on
clinical picture and laboratory diagnosis (Gram stain & Giemsa
stain). It is important to treat the infants with systemic rather
than topical drugs to prevent systemic dissemination of the
organism. As the causative organism is sexually transmitted,
it is vital to treat the mother and her sexual partner(s).
Current WHO guideline for the management of sexually
transmitted infections recommends that all cases of ophthalmia
neonatorum be treated for both N. gonorrhoea and C.
trachomatis39). The co-infection rates are estimated to be
around 2%.39
Ophthalmia neonatorum due to C. trachomatis
WHO and American Academy of Pediatrics recommendation
include oral erythromycin syrup, 50 mg/kg/day, in 4 divided
doses for 14 days.40 Topical erythromycin or tetracycline can
be used as an adjunct therapy. The advantages of oral
erythromycin include eradication of the nasopharyngeal
carriers, treatment of associated pneumonitis and also being
more effective than topical in preventing relapse of
conjunctivitis. 2 Infected partners should receive oral
doxycycline 100 mg twice daily for 7 days or azithromycin 1 g
orally as a single dose.39
Ophthalmia neonatorum due to N. gonorrhoea
Treatment of gonococcal conjunctivitis consists of Intravenous
Penicillin G 100,000 Units /kg/day for 1 week. N. gonorrhoea
isolates are resistant to penicillin in many urban areas in USA.
Across Africa, rates of pencillinase-producing N. gonorrhoea
range from 18 to 57% and many other parts of world (50% to
60%).31,15 Hence a third-generation cephalosporin drug should
be used for 7 days in areas where pencillinase producing
strains are endemic. A single dose of ceftriaxone 50 mg/kg as
s single dose (maximum 125 mg) is highly effective and
recommended by WHO guidelines.41,42 Alternative medications
include spectinomycin 25 mg/kg (maximum 75 mg) as a single
IM dose and kanamycin 25 mg/kg (maximum 75 mg). 43
Infected mother should also be treated with single dose of
ceftriaxone (25-50 mg/kg). The infant’s eye should be
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ISSN: 1985-207X (print), 1985-2274 (electronic)
©Academy of Family Physicians of Malaysia
Online version: http://www.ejournal.afpm.org.my/
frequently irrigated with normal saline to eliminate the
discharge.
Ophthalmia neonatorum due to Herpes simplex virus
Neonates suspected of conjunctivitis due to herpes simplex
should be treated with low dose systemic acyclovir (30mg/kg/
day IV divided tid) or vidarabine (30 mg /kg/day in divided
doses IV) for at least 2 weeks44 to prevent dissemination of
infection. Topical treatment may be with vidarabine ointment
or trifluridine eye drops.
RECOMMENDATIONS AND CONCLUSION
Awareness of the perinatal implications and routine screening
for Chlamydia in pregnant women will provide safer health
care for the mother and her baby. Treatment of any maternal
infection prior to delivery can help reduce the burden of this
disease, and also help to decrease the incidence of childhood
blindness not only in developing nations but also in developed
countries.
References
1. Fransen L, Klauss V. Neonatal ophthalmia in the developing
world. Epidemiology, etiology, management and control. Int
Ophthalmol. 1988;11(3):189-96
2. Scott R Lambert, Conjunctivitis of the newborn (Ophthalmia
Neonatorum). David Taylor & Creig S Hoyt. Pediatric
Ophthalmology and Strabismus, Philadelphia, Elsevers
Saunders, 2005, 146-8.
3. Isenberg S J, Apt L, Wood M. The influence of perinatal infective
factors on ophthalmia neonatorum. J Pediatr Ophthalmol
Strabismus. 1996;33(3):185-8
4. Molgaard TL, Nielsen PB, Kaern J. A study of the incidence of
neonatal conjunctivitis and of its bacterial causes including
Chlamydia trachomatis. Clinical examination, culture and
cytology of tear fluid. Acta Ophthalmol. 1984;62(3):461-71
5. Akera C, Ro S. Medical concerns in the neonatal period. Clinics
in Family Practice. 2003;5(2):265-92
6. Prentice MJ, Hutchinson GR, Taylor-Robinson D. A
microbiological study of neonatal conjunctivae and conjunctivitis.
Br J Ophthalmol. 1997;61(9):601-7
7. Barry WC, Teare EL, Uttley AHC, et al. Chlamydia trachomatis
as a cause of neonatal conjunctivitis. Arch Dis Child.
1986;61(8):797-9
8. Mohile M, Deorari Ashok K, Satpathy G, et al. Microbiological
study of neonatal conjunctivitis with special reference to
Chlamydia trachomatis. Indian J Ophthalmol.
2002;50(4):295-9
9. Shariat H, Young M, Abedin M. An interesting case presentation:
a possible new route for perinatal acquisition of Chlamydia. J
Perinatology. 1992;12(3):300-2
10. Schaller UC, Klauss V. Is Crede’s prophylaxis for ophthalmia
neonatorum still valid? Bull World Health Organ.
2001;79(3):262-6
11. Laga M, Plummer FA, Piot P, et al. Prophylaxis of gonococcal
and Chlamydia ophthalmia neonatorum. N Eng J Med.
1988;318(11):653-7
80
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12. Gururaj AK, Ariffin WA, Vijayakumari S, Reddy TN. Changing
trends in the epidemiology and management of gonococcal
ophthalmia neonatorum. Singapore Med J. 1992;33(3):279-81
13. Lockie P, Leong LK, Louis A. Penicillinase-producing Neisseria
gonorrhoea as a cause of neonatal and adult ophthalmia. Aust
N Z J Ophthalmol. 1986;14(1):49-53
14. Panikabutra K, Ariyarit C, Chitwarakom A. Cefatoxime in the
treatment of gonorrhoea caused by PPNG and non-PPNG. J
Med Assoc Thai. 1982;65(5):271-6
15. Klauss V, Schwartz EC. Other conditions of the outer eye. In:
Johnson GJ, Minassian DC, Weale R, eds. The epidemiology
of eye disease. London, Chapman & Hall, 1998.
16. Johnson D, McKenna H. Bacteria in ophthalmia neonatorum.
Pathology. 1975;7(3):199-201.
17. Meheus A, Piot P. Provision of services for sexually transmitted
diseases in developing countries. In: Oriel JD, Harris JRW, ed.
Recent advances in sexually transmitted diseases. London:
Churchill Livingstone, 1986:261-71.
18. Laga M, Plummer F, Nsanze H, et al. Epidemiology of
ophthalmia neonatorum in Kenya. Lancet. 1986;2:1145-8
19. Darvielle T. Chlamydia trachomatis infections in neonates and
young children. Semin Pediatr Infect Dis. 2005;6(4):235-44
20. Chandler JW, Alexander ER, Pfiffer TA, et al. Ophthalmia
neonatorum associated with maternal chlamydial infection.
Trans Sect Ophthalmo Am Acad Ophthalmol Otolaryngo.
1997;83(2):302-8
21. Walsh C, Anderson LA, Irwin K. Journal of Women’s Health &
Gender- Based Medicine. 2000;9(4):339-43.
22. James J. Champoux, Lawrence Corey, Frederick C. Neidhardt,
et al. Chlamydia: John C. Sherris. Medical Microbiology.United
States of America.Prentice-Hall International Inc 1990, 469-77.
23. Snowe RJ, Wilfert CM. Epidemic reappearance of Gonococcal
ophthalmia neonatorum. Pediatrics. 1973;51(1):110-4
24. Yetman R, Coody D. Conjunctivitis: A practice guideline. J
Pediatric Health Care. 1997;11(5):238-44
25. Goldbloom RB. Prophylaxis for gonococcal and chlamydial
ophthalmia neonatorum. In: Canadian Task Force on the
Periodic Health Examination. Canadian Guide to Clinical
Preventive Health Care. Ottawa: Health Canada 1994; 168-75
26. Beem MO, Saxon EM. Respiratory tract colonization and a
distinctive pneumonia syndrome in infants infected with
chlamydia trachomatis. N Engl J Med. 1997; 296(6):306-10
27. Bradford WL, Kelly HW. Gonococci meningitis in a newborn
infant, with review of the literature. Am J Dis Child. 1933;
46:543-9
28. Nelson LB: Disorders of the conjunctiva. In: Harley’s Pediatric
Ophthalmology. WB Saunders Co; 1998:202-14
29. Gigliotti, Williams WT, Hayden FG, et al. Etiology of acute
conjunctivitis in children. J Pediatr. 1981;98(4):531-6
30. Leibowitz HW, Pratt MV, Flagstad IJ, et al. Human conjunctivitis.
I. Diagnostic evaluation. Arch Ophthalmol. 1976;94(10):1747-9
31. Fransen L, Nsanze H, Klauss V, et al. Ophthalmia neonatorum
in Nairobi, Kenya: The roles of Neisseria gonorrhoea and
Chlamydia trachomatis. J Infect Dis. 1986;153(5):862-9
32. Chlamydial neonatal conjunctivitis and pneumonia 2002.
Accessed on 20 May 2007 at www.chlamydiae.com/restricted/
docs/infections/ophth_neonat.asp
33. Ridway GL, Taylor-Robinson D. Current problems in
microbiology chlamydial infections: which laboratory test? J Clin
Pathol. 1991;44(1):1-5
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 Malaysian Family Physician 2008; Volume 3, Number 2
ISSN: 1985-207X (print), 1985-2274 (electronic)
©Academy of Family Physicians of Malaysia
Online version: http://www.ejournal.afpm.org.my/

34. Talley AR, Garcia-Ferrer KF, Laycock KA, et al. Comparative
diagnosis of neonatal chlamydial conjunctivitis by polymerase
chain reaction and McCoy cell culture. Am J Ophthalmol.
1994;117(1):50-7
35. Crédé CSF. Reports from the obstetrical clinic in Leipzig:
prevention of the eye inflammation in the newborn. Am J Dis
Child. 1971;121(1):3-4
36. Nishida H, Resenberg HM. Silver nitrate ophthalmic solution
and chemical conjunctivitis. Pediatrics. 1975;56(3):368-73
37. Oriel JD. Ophthalmia neonatorum: relative efficacy of current
prophylactic practices and treatment. J Antimicrob Chemother.
1984;14(3):209-20
38. Bell TA, Grayson JT, Krohn MA, et al. Randomized trial of silver
nitrate, erythromycin, and no eye prophylaxis for the prevention
of conjunctivitis among newborn not at risk for gonococcal
ophthalmitis. Pediatrics. 1993;92(6):755-60
39. Guidelines for the management of sexually transmitted
infections 2003. Accessed on 15 Aug 2007 at http://www.who.int/
reproductive-health/publicationa/rhs_01_01_mngt_stis/
guidelines_mngt_stis.pdf
40. AAP, AAOP, Red Book: 2003 Report of the committee on
Infectious Diseases, 26th ed. ELK Grove Village, IL, 2003.
41. Haase Da, Nash Ra, Nsanze H, et al. Single-dose ceftriaxone
therapy of gonococcal ophthalmia neonatorum. Sex Transm
Dis. 1986;13(1):53-55
42. Hoosen AA, Kharsany AB, Ison CA. Single low-dose ceftriaxone
for the treatment of gonococcal ophthalmia –implications for
the national programme for the syndromic management of
sexually transmitted diseases. S Afr Med J. 2002;92(3):238-40
43. Fransen L, Nsanze H, D’Costa L, et al. Single dose kanamycin
therapy of gonococcal ophthalmia neonatorum. Lancet.
1984;2:1234-7
44. Whittey R, Arwin A, Prober C, et al. A controlled trial comparing
vidarabine with acyclovir in neonatal herpes simplex virus
infection. N Engl J Med. 1991;324(7):444-9

Can star fruits kill?

Apparently yes, if you have prior kidney problem. Recently newspaper reported a 66-year-old
Malaysian Chinese who slipped into coma after taking star fruit in China. This problem is noted
only among patients with kidney failure. Star fruit (Averrhoa carambola) has been noted to
cause convulsions, hiccups, or death in uremic patients in many case reports. The exact
constituent causing these effect remains uncertain but oxalate is a prime suspect. Renal patients
should be advised to avoid star fruits.

Here are The Star news reports:

1. Sunday May 18, 2008. Of star fruits and kidneys. http://thestar.com.my/health/
story.asp?file=/2008/5/18/health/21254246&sec=health
2. Monday May 12, 2008. Star fruit victim still in coma. http://thestar.com.my/news/
story.asp?file=/2008/5/12/nation/21221945&sec=nation

Read more about this in PubMed (www.pubmed.gov) by typing “star fruit neurotoxin” (without
quotes) in the search box.

81

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Neonatal Conjunctivitis
Makker K, Kaufman EJ.

Introduction
Neonatal eye discharge is usually congenital nasolacrimal duct obstruction or conjunctivitis. Ophthalmia neonatorum (neonatal conjunctivitis)
presents during the first four weeks of life with eye discharge and hyperemia and is usually an acquired infection during delivery. Incidence in
the United States is around 1% to 2%. It is the most common ocular disease in neonates, and most infections are acquired. Typical symptoms are
persistent tearing and a mucoid discharge in the inner corner of the eye.[1][2][3][4]

Etiology
The age of the baby is an important clue towards the etiology of neonatal conjunctivitis; however, bacterial infections can occur anytime. The
following is a summary of occurrences and causes.[5][6][7]

First 24 hrs of life: Chemical causes like silver nitrate drops or from prophylactic medicines. like erythromycin drops, gentamicin
drops.
24 to 48 hrs of life: Bacterial causes are most likely (Neisseria gonorrhoeae is the most common cause, Staphylococcus aureus).
5 to 14 days of life: Chlamydia trachomatis
6 to 14 days of life: Herpes keratoconjunctivitis
5 to 18 days: Pseudomonas aeruginosa

Epidemiology
The incidence of infectious neonatal conjunctivitis ranges from 1% to 2%.

The epidemiology of neonatal conjunctivitis changed when silver nitrate solution was introduced in the 1800s to prevent gonococcal
ophthalmia.Chlamydia is the most common infectious agent that causes ophthalmia neonatorum in the United States, where 2% to 40% of
neonatal conjunctivitis cases are caused by Chlamydia.

In contrast, the incidence of gonococcal ophthalmia neonatorum has been reduced dramatically and causes less than 1% of cases of neonatal
conjunctivitis.

Pathophysiology
Neonates are at higher risk of conjunctivitis due to many predisposing factors, such as:

Decreased tear production

Lack of IgA in tears
Decreased immune function
Absence of lymphoid tissue in conjunctiva
Decreased lysozyme activity

Risk factors include premature rupture of membranes, prolonged delivery, prematurity, poor prenatal care, maternal STI, mechanical ventilation,
poor hygiene conditions, history of midwife interference, HIV-infected mother.

Neonates at higher risk of congenital lacrimal duct obstruction include those with Down syndrome, Goldenhar Syndrome, clefting syndromes,
midline facial anomalies, hemifacial microsomia, and craniosynostosis.

History and Physical

A purulent discharge, edema, and erythema of the lids and hyperemia of the conjunctiva are suggestive of conjunctivitis. Discharge can be
purulent in bacterial conjunctivitis and watery in viral etiology. Gonorrhea has profuse purulent discharge, Pseudomonas has greenish discharge,
and chlamydia can be watery followed with purulent and bloody discharge.

Laterality, unilateral conjunctivitis most often is seen with S. aureus, P. aeruginosa, Herpes simplex, and adenovirus. Bilateral conjunctivitis is
seen with infection caused by N. gonorrhea or by use of ocular prophylaxis. Chlamydia usually develops in one eye but effects the other after 2
to 7 days.

The physical exam should include evaluation for red reflex, ulcerations (corneal and conjunctival), and adenopathy. One should also rule out
signs of respiratory and systemic infection.

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History of STI in the mother increases the risk of chlamydia and gonorrhea. Neonatal conjunctivitis is frequently diagnosed in neonates born to
HIV-infected mothers.

Evaluation
Differential diagnosis includes eye discharge that can be conjunctivitis or congenital lacrimal duct obstruction. Other diagnoses may be ocular
foreign body, orbital or preseptal cellulitis, entropion, trichiasis, eye trauma (corneal abrasion following delivery), dacryocystitis, keratitis,
subconjunctival hemorrhage (breakage of vessels during delivery), congenital anomalies of nasolacrimal system, corneal epithelial disease,
neonatal abstinence and congenital glaucoma

Physical exam should evaluate for periorbital edema and adenopathy. Examine both eyes/eyelids for swelling and edema, check conjunctiva for
injection (congestion of blood vessels) and chemosis (conjunctival swelling). Check for ulcerations and the presence of red reflex. A purulent
discharge, edema and erythema of the lids, as well as injection of the conjunctiva, are suggestive of bacterial conjunctivitis.

Lab studies include Gram stain and culture to check WBC and bacteria, as well as sensitivity and culture of the bacteria isolated (chocolate agar
and Thayer-Martin media for gonorrhea and blood agar for another medium). A Giemsa stain should be done for chlamydial suspicion.

No imaging and other studies are usually needed, but Fluorescein dye disappearance test can be done to rule out nasolacrimal duct obstruction.

Treatment / Management
General factors important in management include the following:

Avoid cross contamination by frequent hand washing and wearing gloves

Irrigate eye with sterile isotonic saline
Systemic treatment is required for staphylococcal, gonococcal, Chlamydia, Pseudomonas and herpetic conjunctivitis
Avoid eye patching
Consider Pediatric iInfectious disease and/or Pediatric Ophthalmology consult
Chemical conjunctivitis usually resolves with 24 to 72 hours and may be helped with lubrication and artificial tears

Gonococcal conjunctivitis: a medical emergency. Because of PCB resistance, third-generation cephalosporins are the first line antibiotics. It can
happen even with appropriate prophylaxis infants delivered to mothers with positive maternal gonococcal infection.[8][9][10][11][12]

Ceftriaxone 25-50mg/kg intravenous or intramuscular x 1 dose

Alternative is cefotaxime single dose of 100 mg/kg
Isolate the infant during the first 24 hours of parenteral antibiotic therapy
Test for concomitant HIV and syphilis
Evaluate for disseminated disease (arthritis, meningitis, sepsis, anorectal infection)
Consider treating for chlamydia due to high rate of concomitant infection
Keep a low threshold to evaluate for systemic infection (sepsis, meningitis)
Ophthalmology consult since gonococcal conjunctivitis can lead to perforation and blindness
Irrigate the eyes with normal saline at frequent (1 to 2 hour) intervals
Topical antibiotics are not necessary

Chlamydial conjunctivitis: Recommended prophylaxis does not prevent chlamydial conjunctivitis, and topical treatment is ineffective and
unnecessary.

Erythromycin x 14 days or azithromycin 20 mg/kg/day x 3 days is the recommended treatment. However, the American Academy of Pediatrics
still recommends erythromycin because other treatments are not well studied.

A second course is usually required since 1 in 5 cases recur after antibiotic therapy. Pyloric stenosis has been seen in infants less than six weeks
old treated with erythromycin.

For infants born to mothers with chlamydia exposure, there is no prophylaxis recommended but it is important to educate the family to monitor
for infection including pneumonia.

Herpetic conjunctivitis: Administer topical vidarabine or trifluridine five times a day for ten days, evaluate and treat for systemic herpes,
ophthalmology consult is indicated. Systemic treatment with acyclovir is also indicated for SEM (skin eye and mucosa) and central nervous
system infection. Ophthalmologic evaluation is recommended as retinopathy, cataracts and chorioretinitis can develop

Isolation: Isolation of a patient is recommended for Pseudomonas, herpes, and gonococcal conjunctivitis.

Lacrimal Duct Obstruction: Most clear spontaneously without treatment. If the problem doest not resolve and symptoms persist (usually after
6 to 7 months), the infant should be evaluated by an ophthalmologist.

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Enhancing Healthcare Team Outcomes

Neonatal conjunctivitis is not an uncommon problem seen after delivery. When it occurs, the disorder is best managed by a multidisciplinary
team that includes a neonatologist, infectious disease consult, ophthalmologist, pediatrician, pharmacist and a nurse practitioner. There are many
causes of neonatal conjunctivities. Ophthalmia neonatorum (neonatal conjunctivitis) presents during the first four weeks of life with eye
discharge and hyperemia and is usually an acquired infection during delivery. If left untreated it can lead to complications (ulceration and
perforation of the cornea, blindness, chlamydia pneumonia). In severe cases, treatment should be initiated without waiting for culture results.
Empirical treatment should be started soon after sending the culture and tapered once final results are back. The outcomes for most neonates with
conjunctivitis are good.[13] (Level V)

Questions
To access free multiple choice questions on this topic, click here.

References
1. Tan AK. Ophthalmia Neonatorum. N. Engl. J. Med. 2019 Jan 10;380(2):e2. [PubMed: 30625059]
2. Kara M, Kıvanç SA, Olcaysü OO, Akova Budak B, Özmen AT, Kıvanç M, Hörmet Öz HT. The newborn conjunctival flora at the post
delivery 24 hours. J Curr Ophthalmol. 2018 Dec;30(4):348-352. [PMC free article: PMC6276619] [PubMed: 30555969]
3. Fiorito TM, Noor A, Silletti R, Krilov LR. Neonatal Conjunctivitis Caused by Neisseria cinerea: A Case of Mistaken Identity. J Pediatric
Infect Dis Soc. 2018 Nov 21; [PubMed: 30462276]
4. Kaštelan S, Anić Jurica S, Orešković S, Župić T, Herman M, Gverović Antunica A, Marković I, Bakija I. A Survey of Current Prophylactic
Treatment for Ophthalmia Neonatorum in Croatia and a Review of International Preventive Practices. Med. Sci. Monit. 2018 Nov
10;24:8042-8047. [PMC free article: PMC6240167] [PubMed: 30413681]
5. Zikic A, Schünemann H, Wi T, Lincetto O, Broutet N, Santesso N. Treatment of Neonatal Chlamydial Conjunctivitis: A Systematic Review
and Meta-analysis. J Pediatric Infect Dis Soc. 2018 Aug 17;7(3):e107-e115. [PMC free article: PMC6097578] [PubMed: 30007329]
6. Singh G, Galvis A, Das S. Case 1: Eye Discharge in a 10-day-old Neonate Born by Cesarean Delivery. Pediatr Rev. 2018 Apr;39(4):210.
[PubMed: 29610429]
7. Smolkin T, Roth-Ahronson E, Kranzler M, Geffen Y, Mashiach T, Kugelman A, Makhoul IR. Optimizing Accessibility of a Hand-wash Gel
to Infant's Cradle: Effect on Neonatal Conjunctivitis. Pediatr. Infect. Dis. J. 2019 Jan;38(1):e7-e11. [PubMed: 29570175]
8. Gallenga PE, Del Boccio M, Gallenga CE, Neri G, Pennelli A, Toniato E, Lobefalo L, Maritati M, Perri P, Contini C, Del Boccio G.
Diagnosis of a neonatal ophthalmic discharge, Ophthalmia neonatorum, in the molecular age: investigation for a correct therapy. J. Biol.
Regul. Homeost. Agents. 2018 Jan-Feb;32(1):177-184. [PubMed: 29504385]
9. Harding-Esch EM, Kadimpeul J, Sarr B, Sane A, Badji S, Laye M, Sillah A, Burr SE, MacLeod D, Last AR, Holland MJ, Mabey DC, Bailey
RL. Population-based prevalence survey of follicular trachoma and trachomatous trichiasis in the Casamance region of Senegal. BMC Public
Health. 2017 Jul 26;18(1):62. [PMC free article: PMC5530574] [PubMed: 28747198]
10. Fleming-Dutra KE, Nelson JM, Fischer M, Staples JE, Karwowski MP, Mead P, Villanueva J, Renquist CM, Minta AA, Jamieson DJ,
Honein MA, Moore CA, Rasmussen SA. Update: Interim Guidelines for Health Care Providers Caring for Infants and Children with
Possible Zika Virus Infection--United States, February 2016. MMWR Morb. Mortal. Wkly. Rep. 2016 Feb 26;65(7):182-7. [PubMed:
26914500]
11. McAnena L, Knowles SJ, Curry A, Cassidy L. Prevalence of gonococcal conjunctivitis in adults and neonates. Eye (Lond). 2015
Jul;29(7):875-80. [PMC free article: PMC4506339] [PubMed: 25907207]
12. Mayor MT, Roett MA, Uduhiri KA. Diagnosis and management of gonococcal infections. Am Fam Physician. 2012 Nov 15;86(10):931-8.
[PubMed: 23157146]
13. Zuppa AA, D'Andrea V, Catenazzi P, Scorrano A, Romagnoli C. Ophthalmia neonatorum: what kind of prophylaxis? J. Matern. Fetal.
Neonatal. Med. 2011 Jun;24(6):769-73. [PubMed: 21534852]
14. Jin J. Prevention of Gonococcal Eye Infection in Newborns. JAMA. 2019 Jan 29;321(4):414. [PubMed: 30694323]

Publication Details

Author Information

Authors

Kartikeya Makker1; Evan J. Kaufman2.

Affiliations
1
Un of Florida College of Medicine
2
University of Virginia Medical Center

https://www.ncbi.nlm.nih.gov/books/NBK441840/ 3/4
4/29/2019 Neonatal Conjunctivitis - StatPearls - NCBI Bookshelf

Publication History

Last Update: February 15, 2019.

Copyright
Copyright © 2019, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use,
duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is
provided to the Creative Commons license, and any changes made are indicated.

Publisher

StatPearls Publishing, Treasure Island (FL)

NLM Citation

Makker K, Kaufman EJ. Neonatal Conjunctivitis. [Updated 2019 Feb 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-.

https://www.ncbi.nlm.nih.gov/books/NBK441840/ 4/4
 PREGLED
REVIEW
Gynaecol Perinatol 2014;23(4):121–126

*Department of Ophthalmology, Clinical Hospital Dubrava;

**University of Zagreb, School of medicine; ***General Hospital Karlovac;
****Special Hospital for Medical Rehabilitation Stubi~ke Toplice

OPHTHALMIA NEONATORUM
Snje`ana Ka{telan*, Ema Kasun**, @eljko [tajcer***, Boris Kasun****

Review article
Key words: neonatal conjunctivitis, aetiology, clinical features, treatment, prophylaxis
SUMMARY. Ophthalmia neonatorum (ON) or neonatal conjunctivitis is an acute mucopurulent infection of the
conjunctivae occurring within 28 days of life. It is a relatively common disease affecting 1.6% to 12% of all
newborn infants with an increase up to 23% in developing countries. ON can be divided into noninfectious
and infectious categories. The most common noninfectious cause is chemical conjunctivitis whilst the infec-
tious category includes bacterial, chlamydial and viral infections with chlamydia being the most common.
Affected newborns present with a purulent, mucopurulent or mucoid discharge from one or both eyes, in-
jected conjunctiva and lid swelling. In some cases there may also be an association with systemic infection.
The time of onset of conjunctivitis as well as conjunctival scraping can aid in the diagnosis of the specific
aetiology. A number of prophylactic antibiotic or antiseptic agents have been used to prevent ON namely 1%
silver nitrate ophthalmic drops, 0.5% erythromycin or 1% tetracycline ophthalmic ointment and recently a
2.5% povidone-iodine ophthalmic solution. Despite this fact ON still remains a significant cause of ocular mor-
bidity, blindness and even death in underdeveloped countries. The organisms causing ON are transmitted mainly from
the mother’s birth canal during delivery. In countries where the incidence of ON is very low, an alternative prophylaxis
strategy is the introduction of prenatal screening and treatment of infected mothers, forgoing routine neonatal prophy-
laxis and conducting a follow-up of infants after birth for the possible development of infection.

Introduction Generally ON can be divided into noninfectious and

Ophthalmia neonatorum (ON), also called neonatal
conjunctivitis is an acute mucopurulent infection of the
conjunctivae occurring within the first 28 days of life.1,2
It is a relatively common disease caused by chemical,
bacterial or viral processes affecting 1.6% to 12% of all
newborn infants with a marked increase even up to 23%
in developing countries.3,4 The prevalence of ON varies
in different parts of the world and it dependent mainly
upon socioeconomic conditions, the level of knowledge
regarding general health, the standard of maternal
healthcare as well as the implementation of prophylac-
tic programmes.3–5
Prior to the 1880s ON was the primary cause of neo-
natal blindness observed in 60–73% of cases with the
most frequent agent being Neisseria gonorrhoeae pres-
ent in over 10% of live births.5,6 In 1881, Dr Carl Sieg-
mund Franz Credé, a German obstetrician introduced
the application of ocular prophylaxis with 2% silver ni-
trate at birth resulting in a dramatic reduction in the in-
cidence of neonatal gonococcal conjunctivitis from 10%
to 0.3%.5,7 Today in industrialized countries due to a
lower prevalence of sexually transmitted diseases (STD)
in pregnant women and the use of prophylaxis at birth,
blindness caused by ON has become uncommon.6 Since
prophylaxis itself carries a certain risk for the occur-
rence of chemical conjunctivitis some developing coun-
tries have discontinued its routine use. Conversely this
may consequently led to the risk of re-emergence of
these sight threatening infections.8
infectious categories. The most common noninfectious
is chemical conjunctivitis whilst the infectious category
includes bacterial, chlamydial and viral causes with
chlamydia being the most common.5,9 Furthermore in-
fectious agents which the infant may acquire as it passes
through the birth canal include Streptococcus sp., Sta-
phylococcus sp., Escherichia coli, Pseudomonas sp.,
Klebsiella pneumoniae, Haemophilus sp., Neisseria
gonorrhea, and herpes simplex.5 The time of onset of
conjunctivitis as well as conjunctival scraping can aid in
the diagnosis of the specific aetiology of the neonatal
conjunctivitis (Table 1). In differential diagnosis of ocu-
lar inflammation in infants dacryocystitis neonatorum
and preseptal celulitis also need to be taken into consid-
eration.3,4
ON is considered as an ophthalmic emergency. The
neonatal conjunctiva is particularly vulnerable to infec-
tion due to the lack of immunity and the absence of lo-
cal lymphoid tissue at birth. Affected newborns present
with a purulent, mucopurulent or mucoid discharge
from one or both eyes within the first month of life and
typical symptoms of injected conjunctiva and lid swell-
ing. In some cases there may also be an association with
systemic infection which further endangers the in-
fant.1,3,10 Since most cases of infectious conjunctivitis
occur due to transfer of infection in the birth canal dur-
ing delivery the presence of STDs in the mother is the
main risk factor for gonococcal or chlamydial ON.
However the infection may also be spread by people

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Gynaecol Perinatol 2014;23(4):121–126 S. Ka{telan et al. Ophthalmia neonatorum

Table 1. Aetiology and clinical characteristic of neonatal conjunctivitis

Corneal
Aetiology Time of onset Clinical presentation Affected eye
involvement
Chemical First 24 hours Mild lid oedema, mild serous discharge (occasionally purulent), bilateral No
of life self limited, lasts 2–4 days
Chlamydia 5–14 days Variable lid swelling, mild to moderate thick, serous or purulent Unilateral No
trachomatis discharge, erithematous conjunctiva with palpebral more than or bilateral (Rarely eyelid
bulbar involvment scarring or pannus)
Neisseria 2–5 days Hyperacute, severe lid swelling, chemosis, copious, purulent bilateral Oedema, ulcer,
gonorrheae discharge perforation
Bacterial 4–28 days Subacute, variable presentation, depending on organism, mostly mainly Mostly no
lid swelling purulent discharge unilateral Pseudomonas-corneal
perforation
Herpes simplex 1–14 days Mildly injected conjunctiva, serosangvineous discharge,corneal Unilateral Dendritic or
virus epithelial defects, possible vesicular rush on lids or bilateral geographic ulcers

handling the baby soon after birth and more rarely dur-
ing pregnancy due to transplacental passage.1,3,6,10
Incidence
Now days Chlamydia is the most common single
cause of infective neonatal conjunctivitis accounting for
2–40% of cases whilst Neisseria gonorrhoeae is report-
ed in less than 1% of cases. Incidence of these two
pathogens has notably declined in the last two decades
as a result of decreased prevalence of STD in the popu-
lation and the improvement of prenatal screening and
care. Herpes simplex is the cause of ON in less than 1%
of cases whilst non-sexually transmitted bacteria such
as Staphylococcus, Streptococcus, Haemophilus spe-
cies and other Gram-negative bacteria account for the
majority of the remaining ON cases (30–50%).3–5 Apart
from the infectious forms ON also includes chemically
induced conjunctivitis occurring in 10–90% of new-
borns who have been subjected to the instillation of pro-
phylactic agents mostly silver nitrate. Cases of chemical
conjunctivitis are decreasing as silver nitrate prophy-
laxis is being replaced by other agents namely 1% tetra-
cycline and 0.5% erytromxcin ophthalmic ointments.3,6
Although ON in developed countries no longer repre-
sents such a significant public health problem the World
Health Organization (WHO) Vision 2020 »The Right to
Sight, Global Initiative for the Elimination of Avoidable
Blindness« has found that ON is still one of the major
causes of blindness in low-income countries.11 In this
study conjunctivitis affected 17% of neonates which is
consistent with other reports from developing countries
where the rates are even higher such as in Kenya where
the incidence is 23%.12 Iran cites incidence ranging
from 4.9% to 21.7%, with India reporting 0.5 to 33%.
Neonatal conjunctivitis in the United States of America
has an incidence of 1–2%, 2.6–12% in the United King-
dom and in Hong Kong 0.5–5% whilst Norway reported
an 8% incidence.12–16
Management
Diagnosis of ON is made on the basis of clinical find-
ings, incubation period and particularly laboratory re-
sults. In the management of ON corneal examination is
essential in order to exclude keratits or corneal ulcer. In
some cases infectious conjunctivitis may be associated
with systemic complications which must also be ex-
cluded.6,9,10
Laboratory tests
Laboratory studies for neonatal conjunctivitis are es-
sential for proper management and diagnosis. Samples
for testing should be obtained from the inner side of the
eyelid after its evertion. Sampling the exudates is not
adequate since this technique increases the risk of a
false-negative test result. Initial culture on chocolate
agar or a Thayer-Martin test for Neisseria gonorrhoeae
should be obtained as well as blood agar for other bac-
teria. Chlamydial infection can be ruled out using con-
junctival scraping Giemsa stain for intracytoplasmic
inclusion bodies or direct immunofluorescent antibody
assay. Diagnostic tests which reveal bacterial genomes
based on polymerase chain reactions are also available
and useful in laboratory testing. In herpetic conjunctivi-
tis Gram stain may reveal multinucleate giant cells and
Papanicolaou smear may show eosinophilic intranucle-
ar inclusions in epithelial cells. Culture for herpes sim-
plex virus can also be beneficial for diagnostic purpos-
es.1,3,4,7,10
Clinical features and treatment
Chemical conjunctivitis
Chemical conjunctivitis accounts for most cases of
ON presenting with mild irritation, tearing and redness
within the first 24 hours of life.4 It is most commonly
associated with silver nitrate prophylaxis or with other
agents such as erythromycin or tetracycline.3 Chemical
conjunctivitis is a self-limiting condition with spontane-
ous resolution in 2 to 3 days and as such does not re-
quire any diagnostic tests or treatment. However, some
favour the use of preservative free artificial tears or even
antibiotic solution topically in order to prevent second-
ary infection.1,9

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Gonorrhoeal infection
Neisseria gonorrhoeae accounts for less than 1% of
all reported cases of ON.5 In the absence of adequate
prophylaxis, 30% to 42% of infants born by vaginal de-
livery to infected mothers will develop gonococcal ON7
and the transmission rate is even higher in mothers with
concomitant chlamydial infection.9,16
The disease typically presents with profound chemo-
sis, edema of the eyelids and abundant purulent dis-
charge that may be blood-tinged from superficial hem-
orrhage within 2 to 5 days of birth; however, it may
manifest even up to 2 to 3 weeks after delivery.6,7 It is an
established fact that Neisseria gonorrhoeae may pene-
trate intact corneal epithelium causing rapid ulceration
and perforation.7 Thus if left untreated gonorrheal ON
may lead to corneal scarring, ulceration, panophthalmi-
tis and perforation of the globe within 24 hours.4,7
Therefore acute neonatal conjunctivitis should initially
be treated as gonococcal until culture test results be-
come available, after which time the treatment can be
modified based on the laboratory findings.1,3
Infants with gonorrheal ON should be hospitalized
and separated from other babies, treated with frequent
irrigation of the conjunctiva and topical bacitracin or
erythromycin ophthalmic ointment every 2 to 4 hours.
However, topical penicillin is usually unreliable due to
resistance; if sensitivity is established, penicillin drops
should also be used. In the case of corneal involvement
topical atropine is applied. Due to the high prevalence
of penicillin-resistant Neisseria gonorrhoeae, the treat-
ment choice for this organism is a systemic, third-gen-
eration cephalosporin such as ceftriaxone 25 to 50 mg/
kg per day in divided doses administered intravenously
(i.v.) or intramuscularly (i.m.) to a maximum dose of
125 mg during a 7 day period. In addition, a single dose
of cefotaxime 100 mg/kg i.m. may represent an alterna-
tive treatment. Infants with gonorrheal ON should be
mandatorily evaluated for disseminated gonococcal dis-
ease such as arthritis, sepsis and meningitis.1,3,4 The par-
ents should also be evaluated and treated for gonorrhea.1
Infants born to mothers with known gonococcal infec-
tion or no prenatal care should be treated for presump-
tive infection regardless of the absence of visible signs
with a single parenteral dose of cefotaxime 100 mg/kg
or ceftriaxone 25–50 mg/ kg to a maximum dose of 125
mg.5,7,17,18
Bacterial conjunctivitis
Non–sexually transmitted bacteria account for 30%
to 50% of cases of ON and usually have a longer incu-
bation period compared to other infective causes.3–5
They generally present with a subacute onset between
the 4th and 28th day of life. Depending on the pathogen
there may be a diverse clinical picture of a red eye with
lid swelling and a varying amount of purulent discharge.
Specific treatment for infectious neonatal conjunctivitis
is based on the clinical and laboratory findings on Gram,
Giemsa and Papanicolaou stains.1–3
S. Ka{telan et al. Ophthalmia neonatorum
Most bacterial conjunctivitis respond quickly to topi-
cal antibiotic treatment; erythromycin or bacitracin
ointment for gram-positive organisms; gentamicin or
tobramycin drops and ointment for gram-negative or-
ganisms; and established topical antibiotics for Pseudo-
monas.1,3,19 Antibiotic choice may be altered once cul-
ture and sensitivity results become available. In cases of
corneal involvement as seen with virulent organisms
such as Pseudomonas fortified topical antibiotics are
administered and often supplemented by systemic treat-
ment. ON caused by Pseudomonas is rare but can pres-
ent with eyelid edema, erythema and purulent discharge
potentially causing corneal perforation, endophthalmi-
tis, blindness, and even possibly death. Presumptive di-
agnosis can be made using the Gram stain test whilst a
definite diagnosis is based on conjunctival culture
tests.3,4 Systemic antibiotics have poor penetration into
the anterior chamber of the eye and thus in a case of
Pseudomonas infection both systemic and topical ami-
noglycoside antibiotics and in some instances subcon-
junctival injections are required for effective treat-
ment.3,4,19
Chlamydial infection
Chlamydial conjunctivitis has a later onset with less
severe symptoms than gonococcal. It typically occurs
unilaterally or bilaterally from 5 to 14 days after birth or
earlier if membranes rupture prematurely.1,3,20 The clini-
cal manifestations vary from mild conjunctival injection
with scant watery to severe mucopurulent discharge
with eyelid edema, chemosis and pseudomembrane for-
mation.6,10 Loss of vision is very rare. Most cases of
chlamydial infections resolve spontaneously without
complications however if left untreated superficial cor-
neal vascularization and conjunctival scarring may oc-
cur.10 Chlamydial conjunctivitis may also be associated
with preseptal cellulitis and less commonly rhinitis, oti-
tis and pneumonitis. It has been estimated that 2–24%
of pregnant women have chlamydial cervicitis and that
18–50% of infants born to these mothers develop con-
junctivitis whilst 15–20% of infants develop nasopha-
ryngeal infection and 3–18% pneumonia due to C. tra-
chomatis.20
Newborns with conjunctivitis should have specimens
of their conjunctiva and pharynx sent for culture where
diagnosis is made by observing intracytoplasmic inclu-
sion bodies by Giemsa stain or direct immunofluores-
cent assay. Polymerase chain reaction is also a reliable
and efficient test used to prove Chlamydial infec-
tion.1,3,20,21 Treatment of chlamidyal conjunctivitis in-
cludes both topical erythromycin ointment and oral
erythromycin 25 to 50 mg/kg per day divided into four
doses. Typical treatment lasts for 2 weeks in order to
prevent recurrence and secondary pneumonitis.19,20 Ery-
thromycin reports a 20% to 30% failure rate and thus
some infants require a second or occasionally a third
course of antibiotic treatment. Topical treatment alone
is inadequate; since it is unable to eliminate concurrent
nasopharyngeal infection and unnecessary when sys-
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temic treatment is given.19 A small study has demon- Table 2. Differential diagnosis of infectious neonatal conjunctivitis
strated that a short course of oral azithromycin (20 mg/ Associated
kg once daily for 3 days) may be an effective treatment Causes Clinical symptoms
findings
alternative; however further studies are most definitely Neonatal Maternal Lid oedema, discharge, Maternal
necessary.10,19,20 Both parents should also be treated for conjunctivitis infection conjunctival injection sexually
chlamydia even if they are asymptomatic.3,9 Appropriate transmitted
initial therapy for Chlamidyal conjunctivitis prior to or disease
Neonatal Obstruction Epiphora, errithema, Nasal
in the case of inconclusive results from Gram staining, dacryocystitis of lacrimal oedema and tenderness disease
is broad-spectrum antibiotic such as ofloxacin 0.3% system at epicanthal region
four times a day for a week or until the microbiological Periorbital Local spread Marked eyelid oedema, Upper
results become available.10,19,20 cellulitis and errithema, chemosis, respiratory
pain, fever infection
Viral conjunctivitis
Viral conjunctivitis is most commonly caused by ad- presents with an acute onset of pronounced eyelid oe-
enovirus and herpes simplex virus (HSV).1,3,6 Infants dema and erythema, epiphora usually accompanied
with adenovirus ON might present with petechial hem- with pain and fever.1,3,4,21
orrhage or occasionally with large subconjunctival he-
morrhages and associated lymphadenopathy in approxi- Investigations
mately 50% of cases.1
Herpetic conjunctivitis may be the sole manifestation During examination a complete history of previous or
of a neonate infected with HSV. Most cases of herpetic concurrent sexually transmitted disease in the mother as
conjunctivitis are caused by type II; however up to 30% well as results of any cervical cultures obtained during
can be caused by the type I HSV.6,9,22 Onset is acute, pregnancy need to be obtained. Ocular examination
usually 1–14 days after birth with unilateral or bilateral with pen light and fluorescein staining of the newborn is
serosanguinous discharge and in some cases pathogno- a vital part of the procedure. It is important to inspect
monic vesicular skin lesions. Other ocular features may the cornea in every infant with conjunctivitis in order to
include keratitis, usually presenting as microdendrites rule out corneal involvement. Microbiological investi-
or small geographic ulcers, anterior uveitis, cataract, gations should include conjunctival swabs ideally ob-
retinitis and in rare cases optic neuritis. Uncommonly, tained from the everted lid as well as cultures for chla-
systemic infection can cause jaundice, hepatospleno- mydial and viral detection. The Gram staining should
megaly, pneumonitis, meningoencephalitis and dissem- be conducted urgently in the case of suspicion of gono-
coccal conjunctivitis.1,3,4,9,21
inated intravascular coagulation.1,3,6,22 Infants with con-
junctivitis caused by the HSV may be diagnosed late
since they are commonly treated empirically for chla- Complications
mydial or gonococcal infection.4 Newborns showing Potential complications of ON are mainly related to
ocular HSV infection should undergo a complete evalu- gonococcal conjunctivitis whilst most of the other types
ation including lumbar puncture in order to rule out sys- of conjunctivitis in the newborn are fairly benign with-
temic diffusion.1,4,22 Treatment includes systemic acy- out serious consequences. Gonococcal complications
clovir 45–60 mg/kg divided into 3 doses per day for a include keratitis, conjunctival scarring and superior cor-
14 day period coupled with topical ophthalmic solution neal pannus. Since Neisseria gonorrhoeae is a very viru-
1% trifluridine, 0.1% iododeoxyuridine and 3% vidara- lent pathogen with the ability to penetrate the intact epi-
bine or acyclovir 3% ointment.6,22 thelium it may rapidly cause corneal ulcer and perfora-
tion with subsequent endophthalmitis and permanent
Differential diagnosis visual impairment.7,10 Side-effects of treatment such as
the association between oral erythromycin and infantile
As mentioned above in differential diagnosis of ON hypertrophic pyloric stenosis are rarely reported in in-
dacriocystits neonatum and periorbital cellulitis should fants less than 6 weeks.10,20 Further, overwhelming sys-
be considered (Table 2). A blocked nasolacrimal duct is temic infection such as chlamydial pneumonia or dis-
common in newborns resulting in a thick sometimes co- seminated herpes simplex may occur.20,22 Pseudomonas
pious discharge which may be sticky or crusty. This oc- infection is very rare yet may be devastating, causing
curs in 6% of neonates and is usually associated with keratitis and in disseminated cases ultimately lead to
oedema and erythema of the inner canthus. Tearing is death1,3,19 (Table 3).
common and the conjunctiva is usually not affected.
The discharge may be intermittent and responds well to Prognosis
simple cleansing. Purulent drainage can often be ex-
pressed from the punctum. Most babies’ ducts clear as Chlamydial infections have good prognosis with 80%
they grow with the majority functioning normally by 12 of patients showing full recovery after one course of
months of age. Periorbital cellulitis is a serious infec- treatment.20 Bacterial infections with a satisfactory re-
tion preceded by an upper respiratory tract infection. It sponse to medication also have a good prognosis rate.19

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Table 3. Ocular and systemic complications and consequences of neona- strategy of early treatment of infected neonates rather
tal conjunctivitis
than routine prophylaxis has been adopted. In order for
Ocular complications Systemic complications this strategy to be effective regular standard follow-up
Aetiology
and consequences and consequences of infants must be ensured. However, it is seen that
Chemical None (self limited disease) None growing populations, urbanization and increasing pro-
Chlamydia Chronic infection may Pharyngeal colonization, miscuity have caused an increase in the incidence of
trachomatis cause corneal scarring pneumonitis and otitis ON.8,20
and symblepharon media
(adhesion of eyelid to eye) Infants born to mothers without adequate prenatal
Neisseria Corneal ulceration, perforation Meningitis, arthritis, care are the population most at risk for developing ON.
gonorrheae and endophthalmitis (may sepsis, and death Owing to its high association with serious eye and sys-
occur within 24 hr of onset)
temic consequences, neonatal conjunctivitis still re-
Bacterial Pseudomonas sp. may cause Usually none
corneal ulcer, perforation mains an important public health issue worldwide. Al-
and endophthalmitis though not universally accepted some counties such as
Herpes Recurrences throughout life Meningitis and Australia, Sweden, Denmark, Ireland and Great Britain
simplex may cause corneal scarring and disseminated CNS have abandoned the use of routine prophylaxis after
virus profound amblyopia. disease (mortality rate
Chorioretinitis, optic neuritis can be as high as 85%) birth in favour of screening for STDs and better prenatal
and cataracts also may develop care. Consequently, further epidemiological research
and monitoring of the incidence of ON and the preva-
CNS – Central Nervous System lence of the various agents in different parts of the world
are required. With this knowledge preventative and
Furthermore chemical irritations have good outcome treatment strategy options can be adjusted in accordance
with full spontaneous recovery expected after 24–36 to experience with alternative preferences so as to be
hours.1,3 Conversely in the case of viral, gonococcal or applicable for broader use.6,8,18
Pseudomonas infections the ocular involvement may
have a negative effect on visual function and in some Conclusion
cases cause blindness. Further, consequence of accom-
Although in developed countries neonatal conjuncti-
panying systemic dissemination of these agents may vitis is not very common it still represents an important
even be fatal.7,21,22 public health issue worldwide. Preventing neonatal eye
infection by screening and when required treating STDs
Prevention in pregnant women are possible only in countries where
Neonatal conjunctivitis may be prevented by the use medical care is well organized. General screening re-
of topical prophylaxis in the infant or by prenatal screen- quires large financial resources which developing coun-
ing, treatment and follow up of infected mothers.5–7,20 tries cannot sustain and thus eye infection in newborns
The efficacy of maternal screening depends mainly on still represents one of the major health problems in these
the incidence of chlamidial and gonorrhoeal carriers, areas. There is still no optimal agent for efficient pro-
the availability of diagnostic facilities as well as thera- phylaxis of ON whereby the ideal treatment should be
highly and equally effective in the prevention of all in-
py. These measures essentially require an adaptation of
fectious causes particularly chlamydial and gonococcal,
infrastructure and resources including a well organized
whilst simultaneously being non-toxic. Given that gono-
medical system with appropriate antenatal care in order
coccal ophthalmia presents the greatest risk to visual
to screen, diagnose and treat sexually transmitted infec- impairment in newborns, prophylactic and therapeutic
tion in pregnant women. In developing countries this is procedures should be primarily directed against this
frequently not possible where the costs must be com- type of infection.
pared to those of treating infection and complications in
the infant itself.20,23 In the case of routine prophylaxis In summary, since prophylaxis of ON whilst impor-
use it is advised to treat all newborns including those tant is not always effective emphases the need of all in-
born by caesarean section in the first hours of birth.5 volved in the care of newborn babies to acquire greater
Traditionally, this has included the use of 1% silver ni- knowledge and awareness of differential diagnosis and
trate ophthalmic solution.1,3 However, since this treat- proper ON treatment strategies. This understanding can
ment is not successful in all cases and may cause tran- subsequently be applied so as to prevent serious visual
sient chemical conjunctivitis in a high proportion of impairment and blindness that may occur in the case of
newborns, erythromycin and tetracycline ophthalmic unrecognized and untreated neonate eye infections.
ointment have also been introduced as prophylatic
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Addres for correspondance: Snje`ana Ka{telan, Department of
Ophthalmology, University Hospital Dubrava, Avenija Gojka
[u{ka 6, 10000 Zagreb, Croatia. E-mail: snjezanakastelanºya-
hoo.com
Paper received: 2nd November 2014; paper accepted: 17th De-
cember 2014

KONJUNKTIVITIS NOVORO\EN^ADI
Snje`ana Ka{telan, Ema Kasun, @eljko [tajcer, Boris Kasun

Pregledni ~lanak
Klju~ne rije~i: konjunktivitis novoro|en~adi, etiologija, klini~ka slika, lije~enje, prevencija
SA`ETAK. Oftalmija neonatorum (ON) ili konjunktivitis novoro|en~adi je akutna serozno-gnojna upala spojnice koja se
javlja kod djece tijekom prvih 28 dana `ivota. ON se javlja s prevalencijom od 1,6% do 12%, a u zemljama u razvoju ~ak
i do 23%. Mo`e se podijeliti u neupalne i upalne konjunktivitise. Naj~e{}i neinfektivni uzrok je kemijski konjunktivitis
dok infektivni uklju~uju bakterijske, klamidijske i virusne infekcije s klamidijom kao naj~e{}im uzrokom. Klini~ki se
ON manifestira gnojnim, serozno-gnojnim ili seroznim sekretom u jednom ili oba oka, podra`ajem spojnice te otekli-
nom vje|a. U nekim slu~ajevima upala o~iju mo`e biti udru`ena i sa sustavnom infekcijom. Vrijeme pojave konjunkti-
vitisa, kao i nalaz brisa sponice, mo`e pomo}i u postavljanju to~ne etiolo{ke dijagnoze. U prevenciji ON koriste se
razni antibiotici i antisepti~ke tvari poput 1% otopine srebrnog nitrata, 0.5% eritromicinske ili 1% tetraciklinske masti te
od nedavno i 2,5% otopine povidon-jodida. Unato~ uspje{noj prevenciji ON i dalje ostaje zna~ajan uzrok bolesti o~iju,
sljepo}e i ~ak smrti novoro|en~adi, osobito u nerazvijenim zemljama. Uzro~nici novoro|ena~kog konjunktivitisa uglav-
nom se prenose s majke na dijete tijekom poro|aja prolazom kroz poro|ajni kanal. U zemljama u kojima je incidencija
novoro|ena~kog konjunktivitisa vrlo niska, vi{e se ne provodi rutinska profilaksa novoro|en~adi neposredno nakon
poro|aja. Uspje{nim se pokazala alternativna profilaksa koja uklju~uje dobru prenatalnu skrb i lije~enje zara`enih majki
te pra}enje novoro|en~adi nakon ro|enja radi pravovremenog otkrivanja mogu}e infekcije oka.

126
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 10

Ophtalmia Neonatorum
Flora Abazi, Mirlinda Kubati, Blerim Berisha, Masar Gashi,
Dardan Koçinaj and Xhevdet Krasniqi
University Clinical Centre of Kosovo
Republic of Kosovo

1. Introduction
Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are common in
low- income countries. Among adult women STIs (excluding HIV) represent around 9% of the
disease burden (World Bank, 1993). This group of disease (Table 1) can lead to infertility,
abortion, neonatal blindness and sometimes death. Furthermore in up to 75% of women STIs
are thought to be asymptomatic, knowing also that vaginal discharge might be caused by non-
sexually transmitted changes in vaginal flora (Sloan et al., 2000; Lush et al., 2003).

Common STI syndrome Possible cause

Chancroid, Syphilis, Chlamydia, Herpes

Genital ulcer disease
simplex virus, Donovanosis
Urethral discharge Gonorhoea, Chlamydia
Gonorhoea, Chlamydia, Herpes,
Vaginal discharge
trichomonas, Candida, Bacterial vaginosis
Pelvic inflammatory disease Gonorhoea, Chlamydia
Ophtalmia neonatorum Gonorhoea, Chlamydia
Table 1. Common STI syndromes and possible causes Modified from Lush L, Walt G, Ogden
J. (2003) Transferring policies for treating sexually transmitted infections: what’s wrong with
global guidelines? Health Policy and planning 18(1): 18-30.
Ophtalmia neonatorum (neonatal conjunctivitis) is an ocular redness, swelling and drainage
(sometimes even purulent) due to a pathogenic organism or even chemical irritant occurring in
infants less than 4 weeks of age with potentially serious ocular and systemic consequences
(Merck Manual 2006, Rudolph’s 2002). The frequency of this disease varies up to 19% and is
related to prenatal care (Rudolph’s 2002).
Bacterial infection is acquired from infected mother during delivery. The most common
bacteria is Chlamydia trachomatis causing Chlamydial ophtalmia occurring in 2 to 4% of
births. This entity accounts for about one third to half of all conjunctivitis in neonates,
characterizing developed countries (Current, 2009), while the prevalence of maternal
chlamidial infection ranges from 2 to 20% (Mohile et al., 2002) with the incidence increasing
dramatically through years (Miller, 2006).

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148 Conjunctivitis – A Complex and Multifaceted Disorder

Streptococcus pneumoniae and Haemophilus influenze as other bacteria responsible

account for another 15% of cases. On the other hand, the incidence of conjunctivitis due to
Neisseria gonorrhoeae (gonorrheal ophtalmia) in the USA is 2 to 3 per 10,000 births.
Usually the isolation of other bacteria than mentioned above (e.g. Staphylococcus aureus)
represents colonization.
Herpetic kerato- conjunctivitis caused by herpes simplex virus types 1 and 2 represents the
major viral infection, while chemical conjunctivitis is generally secondary to the instillation
of ocular drops (e.g. silver nitrate) for prophylaxis purpose.

2. Etiology
Ophtalmia neonatorum may be caused by microorganisms (infectious etiology), or may be
sterile (non infectious etiology) from chemical irritants (Table 2). Sterile or non infection
ophtalmia neonatorum usually is caused by silver nitrate during prophylaxis of this entity.
As far as infectious etiology concerns there are different bacteria and viruses known to cause
this disease. The most commonly isolated bacteria are: Chlamydia trachomatis and Neisseria
gonorrhoeae; but also: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus
viridians, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Serratia
marcescens, Proteus, Enterobacter, and Pseudomonas species. Also, Eikenella corrodens has
been reported as a cause of neonatal conjunctivitis (Chhabra et al., 2008). The most
commonly viral cause is Herpes simplex virus (HSV) associated most often with a
generalized herpes simplex infection.

Etiology Percentage (%) Incubation period Associated problems

Chemical Varies 1 ---
Chlamydia
2-40 5-14 Pneumonia
trachomatis
Neisseria Disseminated
<1 2-7
gonorrhoeae infection
Disseminated
HSV <1 6-14
infection
Table 2. Pathogens of neonatal conjunctivitis
Modified from "Red Book-Report of the Committee on Infectious Diseases, 29th Edition. The
American Academy of Pediatrics.".http://aapredbook.aappublications.org/.

2.1 Silver nitrate solution

Silver nitrate solution is one the most common sterile causes of ophtalmia neonatorum. It
was used for prophylaxis of ocular gonococcal infections as the most effective agent in
prevention of ophtalmia neonatorum by direct inactivating of Gonococi. Crede's method
was a major advance in preventing of ophtalmia neonatorum using 2% drops of Silver
nitrate (Jatla et al., 2009). Later silver nitrate was found to be toxic for conjunctiva, causing
chemical neonatal conjunctivitis, usually lasting 2-4 days. Because of replacement of silver
nitrate with neomycin and chloramphenicol eye drops, and erythromycin ointment the
incidence of chemical neonatal ophtalmia in the most countries have significantly decreased.

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Ophtalmia Neonatorum 149

2.2 Chlamydia trachomatis

It was postulated that unknown agent acquired from the genital tract of mother, is a cause of
abacterial ophthalmia neonatorum (Kroner, 1884). Lindner comes to conclusion that
inclusion of blennorrhoea was due to the trachoma agent, and after techniques evolution in
Ophtalmology the first isolation was performed by Tang et al. This was realized by using
the yolk sac of embryonated eggs and latter followed by isolating chlamydia from the
babyes eyes with inclusion of blennorrhoea, and also from cervix of mother (Linder, 1909;
T'ang et al., 1957; Jones et al., 1959).
Chlamydia trachomatis is an intracellular parasite, one of the common causes of
ophtalmia neonatorum 2-4% of births. Chlamydia trachomatis, based on immunogenic
epitope analysis of the major outer membrane protein (MOMP), differentiates in 18
serovars. D to K serovars are common urogenital and ocular pathogens. Genotype
classification correlates with the serovar classification previously mentioned (Rodriguez
et al., 1993). Even though this classification is practical and accepted among researchers, it
is found increased frequency of C. trachomatis genotype E in neonatal conjunctivitis
(Lucía et al., 2010).
It is thought that infants may acquire infection from their immediate surroundings, not only
from mother birth canals. The high incidence of caesarean sections with high incidence of
early onset conjunctivitis suggests in a possibility of intrauterine Chlamydial infection due
to rupture of membrane. These kind of infections with Chlamydia trachomatis are sexually
transmitted and WHO estimated 90 million new cases in 1999 (World Health Organisation,
2010). The developing risk of the Chlamydial infection as a conjunctivitis or pneumonia at
birth is increased with an incidence up to 15% (Schachter et al., 1986; Numazaki et al., 2003;
Rosenman et al., 2003).
In some newborns with Chlamydia conjunctivitis, the infection persists too long with panus
and scarring formation and after this, if this infection is left untreated it may be complicated
even with pneumonia. Prevalence of this conjunctivitis is 8%. (Hobson, 1977; Valencia et al.,
2000; Olatunji, 2004).
Chlamydial conjunctivitis occurs after three days of life but may occur up to two weeks of
life with mucopurulent and less inflamed discharge. Chlamydial conjunctivitis is associated
with low risk of blindness compare to Gonorrheal conjunctivitis.

2.3 Neisseria gonorrhoeae

Neisseria gonorrhoeae was identified by Albert Neisser in 1879 in stained smears of
exudates. Availability of Sulfonamides and Penicillin in 1943 was effective in treating of
Gonorroheae (Kampmeier, 1978; Morton, 1977).
In the past N. Gonorroheae was a common cause of conjuctivitis, but after 1881 based on
observations of Crede (using the silver nitrate) the prevalence as a causative agent of
ophtalmia is decreased, in the industrial zones from 10 to 0.3% (Di Bartolomeo et al.,
2001).
Neisseria species are aerobic, gram negative, non motile and non spore forming. Gonococci
occurs in pairs as diplococcal and have outer membrane overlying, a thin peptidoglycan and
cytoplasmic membrane. The species lacks a true polysaccharide capsule but produces a
surface polyphosphate that provides a hydrophilic, negatively charged surface. The
microbes frequently are seen within phagocytes in Gram stains of clinical specimens
(Noegel et al., 1983).

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150 Conjunctivitis – A Complex and Multifaceted Disorder

Gonococci have ability to adhere to mucosal epithelial cells and thus can survive, activating
nuclear factor kappa B and activator protein 1, with release of numerous of cytokines and
chemokines (Nauman et al., 1997; Ramsey et al., 1995).
The individual gonococci can invade, replicate intracellulary, and by exocytosis can exit into
the submucosal space (Alexey et al., 2000; Nauman et al., 1999). This lead in a chemotactic
influx of neutrophils resulting in formation of micorabscesses and exudation of purulent
material into lumen of infected tissues. Infection can persist for weeks to months if
untreated because of escape immune response (Gergg et al., 1983; Casey et al., 1986; Shafer
et al., 1986; Kallstrom et al., 1997).
Incubation period of Neisseria gonorrhoeae in eye infection is 2 to 5 days and in some
cases may arise 2 to 3 weeks (Gutman, 2001). Gonococcal conjunctivitis begins as benign
and bilateral with eyelid edema, followed by chemosis. The discharge in the beginning is
sero-sanguineous, later becomes thick and purulent, and may contain also blood. The
infection can spread if treatment is delayed causing complications such as corneal
ulceration and perforation, iridocyclitis, and panophtalmitis. From conjunctiva
gonococcus can spread to cause gonococcus septicemia, arthritis, and other manifestations
(Friendly, 1969).
Staphylococcus aureus can cause ophtalmia neonatorum with purulent discharge. The
treatment consists in topical or systemic antibiotic. In some cases spontaneous resolution can
occur. Also, in Ophtalmia neonatorum are verified methicillin and erythromycin resistant S.
aureus, but serious ophtalmologic infection was not found. In case of erythromycin-resistant
Staphylococcus aureus conjunctivitis is used erythromycin ointment to prevent ophtalmia
neonatorum (Cimolai, 2006; Hedberg et al., 1990).
The group B Streptococcus also may causes ophtalmia neonatorum, and is resolved after 7
days of treatment (Pöschl et al., 2002).
Eikenella corrodens is a gram-negative bacillus, fastidious, slow growing, and facultative
anaerobic bacterium. It is found as the normal flora of the human mouth, nasopharynx,
gut, and genitourinary tract. In the last two decades has been recognized as cause of head
and neck infections. It is presented as a cause of neonatal conjunctivitis (Chhabra et al.,
2008).
Neonatal conjunctivitis also is caused from other bacteria such as: Staphylococcus
epidermidis, Streptococcus pneumoniae, Haemophilus species, Klebsiella pneumoniae,
Pseudomonas aeruginosa, and Escherichia coli (Martinez et al., 1993; Olatunji et al., 2007).

2.4 Herpes simplex virus

Herpes simplex virus (HSV) can lead to neonatal keratoconjuctivitis passing to the baby
during childbirth. Although it is rare it might be associated with a generalized herpes
simplex infection (Overall, 1994).

2.5 Risk factors of neonatal conjuctivitis

Risk factors of neonatal conjunctivitis may include:
 Maternal infections
 Exposure of the infant to infectious organisms
 Increased birth weight
 Inadequacy of ocular prophylaxis immediately after birth (Gichuhi et al., 2009)
 Premature Rupture Of Membranes (Wu et al., 2009)

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Ophtalmia Neonatorum 151

 Ocular trauma during delivery

 Mechanical ventilation
 Prematurity
 Poor prenatal care
 Poor hygienic delivery conditions
 Post-delivery infection due to direct contact with health care workers or by
environment
 Silver nitrate exposure

3. Clinical findings
The Clinical presentation of Neonatal Conjuctivitis varies depending upon the severity and
the type of infection. The signs and symptoms of ophthalmia neonatorum are similar for
most of the infectious agents (Foster, 1995). Diffuse unilateral or bilateral redness due to
injection of conjuctival vessels is the hallmark. Other common findings incude conjuctival
oedema and discharge. More serious finding include keratitis and orbital celulitis, but also
serious systemic involvement if left untreated (Woods, 2005; Zar, 2005). It is necessary to
make accurate diagnosis in order to begin appropriate treatment which can help to reduce
complications (Table 3).

3.1 Chemical conjunctivitis

It is present with mild injection of conjunctiva with minimal discharge. It is important that
these occur within few hours after application of irritant. Sometimes the persistent redness
of the eye might be folowed by purulent discharge and in that case there is a need for
further laboratory investigation.

3.2 Bacterial conjunctivitis

The occurrence time and severity of clinical features depend on the type of microorganism.
Gonococal conjunctivitis
During this infection there is a severe redness, swelling of conjunctiva and eyeleads, and a
lot of purulent drainage presenting few days after birth (Woods 2005), but may occur later
as hyperacute conjunctival injection and chemosis, lid oedema and severe purulent
discharge. Corneal ulceration and perforation may be associated features (Jackson, 2008).
Hyperacute conjunctivitis has the incubation period 1-7 days (Isenberg et al., 1996; Chandler
et al., 1990), often bilateral and signs are more severe. Serosanguinous exudate may be
replaced by mucopurulent discharge, with development of membranes. A disseminated
gonococcal infection with arthritis, meningitis, pneumonia and sepsis that may lead to death
of an infant is very rare.
Chlamydial conjunctivitis
Cervical infection with Chlamydia carries a risk to the neonate of 18-50% (Vaz et al., 1999;
Schachter et al., 1986; Hollier et al., 2009; Roberts, 2009). The clinical features present at 5 to
14 days after birth with gradually worsening. Eyelids and conjunctiva are redness and
swollen (Figure 1), and mucopurrulent drainage is present. It may also occur severe
swelling and discharge with a course of 6 to 12 weeks (if left untreated) leading to scars of

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152 Conjunctivitis – A Complex and Multifaceted Disorder

conjunctiva and cornea. In this case, if untreated or even only topically treated, may worsen
with upper respiratory infection, in severe cases with afebrile pneumonitis usually
presenting at 2 to 20 months of age (Darville, 2005). Approximately 50% of infants with
chlamydial pneumonitis have concurrent conjunctivitis or a recent history of conjunctivitis
(Tarabishy et al., 2008).

Fig. 1. Neonatal conjuctivitis due to chlamydia trachomatis in a five days old infant
Staphylococcus conjunctivitis. Staphylococcus aureus can cause neonatal conjuctivitis with
redness, swollen purulent discharge (Figure 2).

Fig. 2. Neonatal conjuctivitis due to staphylococcus aureus infection in an one week old
infant.

3.3 Herpetic conjunctivitis

It is present usually the first two weeks of life with moderate injection, edema of conjuctiva
and nonpurrulent discharge after vesicular skin lesions which can precede the eye
involvment. In some cases it may be complicated with corneal clouding with dentritic or
geographic corneal ulcers or upper respiratory infection (Rudolph, 2002). Systemic infection
can cause jaundice, hepatosplenomegaly, pneumonitis, meningoencephalitis and
disseminated intravascular coagulation.

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Ophtalmia Neonatorum 153

Etiology Onset after birth Clinical findings

Mild injection, watery

Chemical 3-36 hours
dicharge

Injection and lead edema,

Gonnococal 1-7 days
purulent discharge

Mild- severe injection, watery-

purulent discharge,
Chlamydial 5-14 days
psudomembranes, chronicity,
associated pneumonia
Watery discharge, injection
Herpetic 1-14 days and lead edema, associated
keratitis

Table 3. Clinical findings of neonatal conjunctivitis by etiological factor modified from

Rudolph’s fundametntals of Pediatrics, 2002

4. Diagnosis
Prompt diagnosis is key in establishing proper treatment and minimizing potential serious
complications of disease. An accurate diagnosis of conjunctivitis centers on taking a patient
history to learn when symptoms began, how long the condition has been going on, the
symptoms experienced, and other predisposing factors, such as upper respiratory
complaints, allergies, sexually transmitted diseases, herpes simplex infections, and exposure
to persons with pink eye. It may be helpful to learn whether an aspect of an individual's
occupation may be the cause.
A thorough examination of the globe and periocular structures of a neonate suspected to
have neonatal conjunctivitis is crucial. Corneal involvement should be investigated closely
with and without fluorescein and blue cobalt light. Non-specific signs of neonatal
conjunctivitis include conjunctival injection, tearing, mucopurulent or non-purulent
discharge, chemosis, and eyelid swelling.
Diagnostic tests are usually not indicated unless initial treatment fails or an infection with
gonorrhea or chlamydia is suspected. In such cases, the discharge may be cultured and
stained to determine the organism responsible for causing the condition. Cultures and
smears are relatively painless (Jackson, 2008).
Laboratory studies for suspected infectious etiology should include the following (Table 4
and 5):
 Conjunctival scraping, stains for Chlamydia. C. trachomatis is an obligate intracellular
organism and exudates are not adequate for testing so conjunctival specimens for
chlamydia testing must include conjunctival epithelial cells;
 Culture on chocolate agar for N gonorrhoeae ;

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154 Conjunctivitis – A Complex and Multifaceted Disorder

 Culture on blood agar for other strains of bacteria;

 Culture for HSV if vesicles present or is supicious of viral etiology;
 Direct antibody testing or Polymerase Chain Reaction (PCR) may also be indicated.
The laboratory studies may need to be repeated if symptoms worsen or recur following
treatment.

Etiology Laboratory diagnosis

Chemical -

Gonnococal Stain and cultures

Stain, cultures, enzyme immunoassay, direct fluorescent
Chlamydial
antibody assay
Herpetic Stain, cultures, antigen or DNA assay

Table 4. Laboratory diagnosis based on etiology

Modified from Rudolph’s fundametntals of Pediatrics, 2002

Etiology Conjuctival Scraping

Minimal reactive cells to few
Chemical
polymorphonuclears
Many reactive cells with gram
Gonococcal
negative intracellular dyplococci
Many reactive cells with stain for
basophilic cytoplasmic inclusion
Chlamydial
bodies or direct immunofluorescent
assay
Other bacteria (Staphylococcus,
Stain for bacteria
Streptococcus, Haemophilus)
Variable reactive cells with
Herpes simplex virus
multinucleated giant cells

Table 5. Conjuctival scraping findings in ophtalmia neonatorum

Modified from Duane's Clinical Ophthalmology, 2008

5. Differential diagnosis
The differential diagnosis of neonatal conjunctivitis includes:
 Cellulitis (Orbital, Preseptal)
 Dacryocystitis
 Glaucoma, Primary or Secondary Congenital
 Keratitis, Bacterial, Fungal or Herpes Simplex

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Ophtalmia Neonatorum 155

6. Complications
Complications usually can be divided concerning eye and/or systemic complications.
Ocular complications of neonatal conjunctivitis include pseudomembrane formation,
corneal edema, thickened palpebral conjunctivia, peripheral pannus formation, corneal
opacification, staphyloma, corneal perforation, endophthalmitis, loss of eye, and blindness.
Systemic complication due to Chlamydia infection
Systemic complications of chlamydia conjunctivitis include pneumonitis, otitis, pharyngeal
and rectal colonization. Pneumonia has been reported in 10-20% of infants with chlamydial
conjunctivitis.
Systemic complications due to gonococcal infection
Complications of gonococcal conjunctivitis and subsquent systemic involvement include
arthritis, meningitis, anorectal infection, septicemia, and death.
The complications can be avoided if the proper treatment is initiated at time.

7. Treatment
7.1 Initial therapy
Ophtalmia neonatorum is treated with a broad-spectrum antibiotic e.g. ofloxacin 0.3% qds.
When the microbiological results is present the treatment is based on microbiological cause
(Jackason, 2008).

7.2 Chemical ophtalmia neonatorum

Chemical neonatal conjunctivitis usually disappears spontaneously within 2-4 days, and no
treatment is required. The use of artificial tear is preferred.

7.3 Chlamydial ophtalmia neonatorum

The recommended regimen for chlamydial neonatal conjunctivitis is erythromycin base or
ethylsuccinate, as a systemic therapy, 50mg per kg per day orally, divided into four doses
per day for two weeks (Table 6). A follow-up of infants is recommended to determine
whether initial treatment was effective because the efficacy is only approximately 80% and a
second course of therapy might be required. Also, the evaluation of concomitant chlamydial
pneumonia should be considered (Sexually transmitted disease treatment guidelines, 2010;
Lippincott Williams & Wilkins, 2008; Yanoff & Duker, 2008).
The systemic treatment is administred as additional to topical treatment. (Sexually
transmitted disease treatment guidelines, 2010). From local antibiotics usually are applied
erythromycin 0.5% or tetracycline 1% eye ointment.
The mother and her sexual partners also should be treated with erythromycin base or
ethylsuccinate (Sexually transmitted disease treatment guidelines, 2010).

7.4 Gonococcal ophtalmia neonatorum

The immediate treatment is needed because of complications such as corneal perforation
and blindness. Gonococcus conjunctivitis is treated with ceftriaxone 25-50mg/kg IV or IM in
a single dose (Table 6), not to exceed 125mg. An alternative regimen is cefotaxime
100mg/kg/24 hours IV or IM divided in two doses for seven days or 100mg/kg as a single
dose. The irrigation with saline is preferred until the purulent discharge is cleared. The local

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156 Conjunctivitis – A Complex and Multifaceted Disorder

antibiotics such as bacitracin or erythromycin eye ointment are applied as additional

therapy because topical antibiotic alone is inadequate. The atropine sulphate ointment
should be applied if the cornea is involved (Sexually transmitted disease treatment
guidelines, 2010; Lippincott Williams & Wilkins, 2008; Yanoff & Duker, 2008).
The mothers of infants and mother’s sex partners should be evaluated and treated according
to the recommendations for treating gonococcus infections in adults (Sexually transmitted
disease treatment guidelines, 2010).
Neonatal conjunctivitis due to other bacteria usually respond to topical ointments
containing bacitracin for gram positive stain bacteria, and tobramycin or ciprofloxacin for
gram negative stain bacteria.

Type of bacteria Drug Dose for day Duration

Chlamydia
Erythromycin 50mg/kg 14 days
trachomatis
Nesseria gonorrhoeae Ceftriaxone 25-50mg/kg A single dose

Table 6. Recommended regimens for bacterial neonatal conjuctivitis

Modified from Sexually transmitted disease treatment guidelines 2010. Centers for Disease
Control and Prevention, MMWR Recomm Rep 2010; 59 (RR-12): 53-54.

7.5 Herpetic ophtalmia neonatorum

Herpetic neonatal conjunctivitis is recommended to be treated with acyclovir 45-
60mg/kg/day in three doses for 14 days in non disseminated disease and 21 days in
disseminated disease. Local antiviral therapy is 1% trifluridine or 3% vidarabine or 0.1%
iododeoxyuridine (drops or ointment) (Lippincott Williams & Wilkins, 2008).

8. Prophylaxis
8.1 Silver nitrate prophylaxis
German obstetrician Credé', in 1881, has applied 2% silver nitrate solution for prophylaxis of
neonatal ophtalmia, resulting in a reduction of incidence from 7.8% to 0.17%. Thereafter was
started instillation of silver nitrate, based on legislation, in most European countries and
most of North America states in the first half of last century (Schneider, 1984; Crede CSR,
1881; Barasam, 1966). Latest in 1970s approximately half the United States specified 1%
silver nitrate solution as the sole agent (Hammerschlag MR et al., 1908). In the United
Kingdom the procedure has been discontinued, and in Japan and Australia, it was never
used (Shaw EB, 1977). The mother usually can be representative consent of using of Credé's
method in Sweden (Wahlberg V, 1982). The decision for changing of the Wisconsin law in
1980 that tetracycline and erythromycin could be used for prophylaxis against GON was
based on a previous ruling by US Supreme Court (Whittaker N et al., 1981).
The siver nitrate, which by law is instilled within 1 hour after birth, may cause chemical
conjunctivitis pain and visual impairment. The silver nitrate does not prevent all cases of
gonococcal neonatal conjunctivitis. The chemical conjunctivitis caused by silver nitrate may
mask the onset of gonococcus neonatal conjunctivitis (Shaw, 1977; Snowe et al., 1973).

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Ophtalmia Neonatorum 157

Since 1940s, when antibiotics were developed the incidence of gonococcal neonatal
conjunctivitis was decreased dramatically (Butterfield et al., 1981).
Recommendations of the US Centers for Disease Control (CDC) are supported from
American Academy of Pediatrics in 1986 and 1988. According to these recommendations 1%
tetracycline ointment and 0.5% erythromycin ointment were equally acceptable in
preventing of gonococcus ophtalmia neonatorum. Although it was felt that silver nitrate
might be the best agent in areas where the incidence of penicillinase-producing neisseria
gonorrhoeae (PPNG) was appreciable (Peter, 1988).
The CDC's 1989 guidelines on the treatment of sexually transmitted diseases were
unchanged with respect to the prevention of ophthalmia neonatorum (Sexually Transmitted
Diseases Treatment Guidelines, 1989).
In Canada the incidence of PPNG among reported cases of gonorrhea increased from 0.5%
in 1985 to 5.5% in 1989 (Status of penicillinase-producing Neisseria gonorrhoeae in
Canada, 1991).
In 1989 the US Preventive Services Task Force recommended that 1% tetracycline ointment or
0.5% erythromycin ointment have to be applied topically to the eyes of all newborns as soon as
possible after birth and no later than 1 hour after birth (Preventive Services task Forces, 1989).
Silver nitrate was not recommended since it is locally irritating, frequently causing chemical
conjunctivitis, and has limited efficacy in preventing chlamydial ophthalmia neonatorum.

8.2 Povidon-iodine prophylaxis

In 1995, is reported the use of a 2.5% povidone-iodine solution for prophylaxis of ophtalmia
neonatorum in Kenya, and was found to be more effective than treatment with
erythromycin or silver nitrate for prophylactic purposes. Also, the povidone-iodine was less
toxic and it costs less (Isenberg et al., 1995).
The povidone-iodine prophylaxis against ophtalmia neonatorum, applied twice in the first
postnatal day over a single application at birth, revealed with no advantage. It was
supported the original notion of Crede in 1881 that a single drop of an effective medication
given at birth is the best way to prevent the development of ophtalmia neonatorum. The
povidone-iodine applications approximately 24 hours later were with no further benefit.

8.3 Antibiotics prophylaxis

The procedure for prevence of gonococcal ophthalmia neonatorum is required by law in
most states. Prophylactic agent should be instilled into the eyes of newborns. But, the
efficacy of prophylactic agents in preventing chlamydial ophthalmia is clearless, and they
do not eliminate nasopharyngeal colonization by C. trachomatis.
This preparation should be instilled into both eyes of every neonate as soon as possible after
delivery. Ideally, ointment should be applied using single-use tubes or ampoules rather than
multiple-use tubes. If prophylaxis is delayed (i.e., not administered in the delivery room), a
monitoring system should be established to ensure that all infants receive prophylaxis. All
infants should be administered ocular prophylaxis, regardless of whether they are delivered
vaginally or by cesarean section.
Antibiotics that are applied in prevention of gonococcal ophtalmia are tetracycline and
erythromycin and are more effective than silver nitrate (Rothenberg, 1979; American Academy
of Pediatrics, 1980). Erythromycin is less effective than tetracycline against sensitive isolates of
N. gonorrhoeae in vitro. Canadian Paediatric Society in 2010 has revised recommandations for
the prevention of neonatal ophthalmia due to N gonorrhoeae (Table 7).

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158 Conjunctivitis – A Complex and Multifaceted Disorder

Recommendation Category Grade

Prophylaxis to prevent neonatal ophthalmia due to N gonorrhoeae
A 1
should be provided to all infants.
Physicians and their patients may choose among the recommended
prophylactic agents - that is, 1% silver nitrate solution in single-
A 1
dose ampoules, or an ointment containing 0.5% erythromycin base
or 1% tetracycline hydrochloride in single-dose tubes.
The use of povidone-iodine for ophthalmia prophylaxis. C 1
To prevent potential cross-contamination, a separate ampoule or
tube should be used for each eye. Ampoules and tubes should be A 3
discarded after use.
When 1% silver nitrate solution is used, each eyelid should first be
wiped gently with a sterile cotton ball to remove foreign matter and
permit adequate eversion of the lower lid. Two drops of solution are
placed in each lower conjunctival sac. The closed eyelids can be A 3
massaged gently to help spread the solution to all areas of the
conjunctiva. After 1 min, any excess silver nitrate should be gently
wiped from the eyelids and surrounding skin with sterile cotton.
When an ophthalmic ointment (tetracycline or erythromycin) is used,
the eyelids should be prepared as for the application of silver nitrate.
A line of ointment 1 to 2 cm long is placed in each lower conjunctival
sac, if possible covering the whole lower conjunctival area. Care is
A 3
needed to prevent injury to the eye or the eyelid from the tip of the
tube. The closed eyelids can be massaged gently to help spread the
ointment. After 1 min, any excess ointment should be wiped gently
from the eyelids and surrounding skin with a sterile cotton.
The eyes should not be irrigated after instillation of a prophylactic
agent. Irrigation may reduce the efficacy of the agent and probably
A 3
does not decrease the incidence of chemical conjunctivitis caused
by silver nitrate.
Prophylaxis should be given as soon as possible after birth.
However, delaying prophylaxis for up to 1 h after birth probably B 3
does not impair the agent's efficacy.
A check system should be established to ensure that all infants are
A 3
treated.
Infants born by caesarian section should also receive prophylaxis. B 3
Pregnant women should be screened for infection by N
gonorrheoae and C trachomatis during pregnancy and their A 3
identified infections should be treated during pregnancy.
Infants born to women with gonococcal infection discovered
during labour or at the time of delivery should be given a single
A 2
dose of ceftriaxone (25 to 50 mg/kg) or cefotaxime (100 mg/kg) in
addition to topical prophylaxis.

Table 7. Recommandations for the prevention of neonatal ophthalmia due to N gonorrhoeae

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Ophtalmia Neonatorum 159

Modified from Canadian Pediatric Society. Revised Recommandations for the prevention of
neonatal ophtalmia, 2010.
Classification used to determine the strength of the recommendations and the quality of the
evidence on which the recommendations are based.

Category Definition
A Good evidence to support a recommendation for use
B Moderate evidence to support a recommendation for use
C Insufficient evidence to support a recommendation for or against use
D Moderate evidence to support a recommendation against use
E Good evidence to support a recommendation against use

Grade
1 Evidence from at least one properly randomized, controlled trial
Evidence from at least one well-designed clinical trial without
randomization, from cohort or case- controlled analytic studies, preferably
2
from more than one centre, from multiple time series, or from dramatic
results in uncontrolled experiments
Evidence from opinions or respected authorities on the basis of clinical
3
experience, descriptive studies or reports of expert committees
Source. Canadian Pediatric Society. Revised Recommandations for the prevention of neonatal
ophtalmia, 2010.
Table 8.
Tetracycline as silver nitrate does not prevent completely chlamydial ophtalmia neonatorum
(Laga et al., 1988, Canadian Task Force on the Periodic Health Examination, 1992). There
were no significant differences between the rates of chlamydial ophtalmia neonatorum
when prophylaxis with erythromycin was compared with prophylaxis with tetracycline or
silver nitrate. For a modest reduction in chlamydial ophtalmia neonatorum now are
recommended the agents for gonococcal prophylaxis.
Erythromycin 0.5 % is the only antibiotic ointment recommended for use in neonates in each
eye in a single application. Silver nitrate and tetracycline ophthalmic ointment are no longer
manufactured in the United States, bacitracin is not effective, while povidone iodine has not
been studied adequately (Sexually Transmitted Diseases Treatment Guidelines, 2010).
If erythromycin ointment is not available, infants at risk for exposure to N. gonorrhoeae
(especially those born to a mother with untreated gonococcus infection or who has received
no prenatal care) can be administered ceftriaxone 25-50 mg/kg IV or IM, not to exceed 125
mg in a single dose (Sexually Transmitted Diseases Treatment Guidelines, 2010).
The diagnosis and treatment of gonococcal and chlamydial infections in pregnant women
is the best method for preventing neonatal gonococcal and chlamydial disease. Also
preventative measures include proper hand-washing techniques by peripartum and
nursery staff.

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160 Conjunctivitis – A Complex and Multifaceted Disorder

9. Prognosis
 Chlamydial infection: good - 80% fully recover after one course of treatment.
 Bacterial infection: rarely fails to respond to appropriate treatment.
 Viral infection: the ocular prognosis can be poor and the systemic sequelae may be fatal.
 Chemical irritation: good - full spontaneous recovery expected after 24-36 hours.

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 Conjunctivitis - A Complex and Multifaceted Disorder
Edited by Prof. Zdenek Pelikan

ISBN 978-953-307-750-5
Hard cover, 232 pages
Publisher InTech
Published online 23, November, 2011
Published in print edition November, 2011

This book presents a number of interesting and useful aspects and facets concerning the clinical features,
properties and therapeutical management of this condition. Dr. H. Mejía-López et al. present an interesting
survey of the world-wide epidemiologic aspects of infectious conjunctivitis. Dr. U. Ubani evaluates conjunctival
symptoms/signs participating in the clinical features of this disorder. Dr. A. Robles-Contreras et al. discuss
immunologic aspects underlying possibly the conjunctivitis. Dr. Z. Pelikan presents the cytologic and
concentration changes of some mediators and cytokines in the tears accompanying the secondary conjunctival
response induced by the nasal challenge with allergen. Dr. S. Sahoo et al. summarize the treatment and
pharmacologic control of particular clinical forms of conjunctivitis in general practice. Dr. S. Leonardi et al.
explain the basic pharmacologic effects of leukotriene antagonists and their use for the treatment of allergic
conjunctivitis. Dr. J.A. Capriotti et al. evaluate the therapeutical effects of various anti-adenoviral agents on the
acute conjunctivitis caused by adenovirus. Dr. V. Vanzzini-Zago et al. assess the prophylactic use and efficacy
of "povidone-iodium solution", prior the ocular surgery. Dr. F. Abazi et al. present the clinical features,
diagnostic and therapeutical aspects of "neonatal conjunctivitis". Dr. I.A. Chaudhry et al. review the special
sub-form of conjunctivitis, being a part of the "Trachoma". Dr. B. Kwiatkowska and Dr. M. Maślińska describe
the clinical, pathophysiologic and immunologic features of conjunctivitis. Dr. S. Naem reviews the conjunctivitis
form caused by Thelazia nematodes, occurring principally in animals.

How to reference
In order to correctly reference this scholarly work, feel free to copy and paste the following:

Flora Abazi, Mirlinda Kubati, Blerim Berisha, Masar Gashi, Dardan Koçinaj and Xhevdet Krasniqi (2011).
Ophtalmia Neonatorum, Conjunctivitis - A Complex and Multifaceted Disorder, Prof. Zdenek Pelikan (Ed.),
ISBN: 978-953-307-750-5, InTech, Available from: http://www.intechopen.com/books/conjunctivitis-a-complex-
and-multifaceted-disorder/ophtalmia-neonatorum

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CHAPTER 20

External Diseases of the Eye

This chapter focuses on external diseases of the eye that are seen in the pediatric population. Many of the topics covered in this chapter are also discussed in BCSC Section 8, External Disease and Cornea.

Infectious Conjunctivitis

Bacterial and viral infections are the most common causes of infectious conjunctivitis in children in developed countries. Presenting symptoms of infectious conjunctivitis commonly include burning,
stinging, and foreign-body sensation; signs include conjunctival hyperemia, ocular discharge, and matting of the eyelids. Symptoms and signs may be present unilaterally or bilaterally. The character of the
discharge is diagnostically helpful and may be serous, mucopurulent, or purulent. Purulent discharge suggests a polymorphonuclear response to a bacterial infection, mucopurulent discharge suggests a
viral or chlamydial infection, and a serous or watery discharge suggests a viral or allergic reaction. Membrane or pseudomembrane formation may occur in severe viral or bacterial conjunctivitis, Stevens-
Johnson syndrome, ligneous conjunctivitis, and chemical burns. Table 20-1 lists common causes of conjunctival hyperemia, or red eye, in infants and children.

Table 20-1

Ophthalmia Neonatorum
Ophthalmia neonatorum refers to conjunctivitis occurring in the rst month of life. This condition can be caused by bacterial, viral, or chemical agents. Widespread e ective prophylaxis has diminished its
occurrence to very low levels in industrialized countries, but ophthalmia neonatorum remains a signi cant cause of ocular infection, blindness, and even death in medically underserved areas around the
world.

Epidemiology and etiology

Worldwide, the incidence of ophthalmia neonatorum is greater in areas with high rates of sexually transmitted disease and poor health care. The prevalence ranges from 0.1% in highly developed
countries with e ective prenatal and perinatal care to 10% in areas such as East Africa. Because a mother may have multiple sexually transmitted diseases, infants with one type of ophthalmia neonatorum
should be screened for other such diseases. Public health authorities should be contacted to initiate evaluation and treatment of other maternal contacts in cases of sexually transmitted diseases.
The causative organism usually infects the infant through direct contact during passage through the birth canal. Infection can ascend to the uterus, especially if there is prolonged rupture of membranes,
so even with cesarean delivery, infants can be infected.
Neisseria gonorrhoeae Ophthalmia neonatorum caused by Neisseria gonorrhoeae typically presents in the rst 3–4 days of life. Patients may present with mild conjunctival hyperemia and ocular discharge.
In severe cases, there is marked chemosis, copious discharge, and potentially rapid corneal ulceration and perforation (Fig 20-1). Systemic infection can cause sepsis, meningitis, and arthritis.
 Figure 20-1 Neisseria gonorrhoeae conjunctivitis. (Courtesy of Jane C. Edmond, MD.)

Gram stain of the conjunctival exudate showing gram-negative intracellular diplococci allows a presumptive diagnosis of N gonorrhoeae infection; treatment should be started immediately. Ophthalmia
neonatorum from Neisseria meningitidis has also been reported. De nitive diagnosis is based on culture of the conjunctival discharge. Treatment of gonococcal ophthalmia neonatorum includes systemic
ceftriaxone and topical irrigation with saline. Topical antibiotics may also be indicated if there is corneal involvement.

Chlamydia trachomatis Chlamydia trachomatis is an obligate intracellular bacterium that can cause neonatal inclusion conjunctivitis. Onset of conjunctivitis usually occurs around 1 week of age, although
it may be earlier, especially in cases with premature rupture of membranes. Eye infection is characterized by minimal to moderate lmy discharge, mild swelling of the eyelids, and hyperemia with a
papillary reaction of the conjunctiva (Fig 20-2). Severe cases may be accompanied by more copious discharge and pseudomembrane formation. Chlamydial infection in infants di ers from that in adults in
several ways: in infants, membrane formation may occur, the amount of mucopurulent discharge is greater, and there is no follicular response.

Figure 20-2 Chlamydial ophthalmia neonatorum. (Courtesy of Jane C. Edmond, MD.)

Chlamydial infections can be diagnosed by culture of conjunctival scrapings, polymerase chain reaction, direct uorescent antibody tests, and enzyme immunoassays. Systemic treatment of neonatal
chlamydial disease is indicated because of the risk of pneumonitis and otitis media. The treatment of choice is oral erythromycin, 50 mg/kg per day in 4 divided doses for 14 days. Topical erythromycin
ointment may be used in addition to but not as a replacement for oral therapy.

Herpes simplex virus Infection with herpes simplex virus (HSV) is usually secondary to HSV type 2 and typically presents later than infection with N gonorrhoeae or C trachomatis, frequently in the second
week of life. See the discussion of congenital HSV infection in Chapter 28.

Chemical conjunctivitis
Chemical conjunctivitis refers to a mild, self-limited irritation and redness of the conjunctiva occurring in the rst 24 hours after instillation of silver nitrate, a preparation used for ophthalmia neonatorum
prophylaxis. This condition improves spontaneously by the second day of life.

Ophthalmia neonatorum prophylaxis

Originally, 2% silver nitrate was used as prophylactic treatment of gonorrheal ophthalmia neonatorum. However, it is not e ective against C trachomatis and has largely been supplanted by agents that are
e ective against both N gonorrhoeae and C trachomatis, such as erythromycin and tetracycline ointments and 2.5% povidone-iodine solution. Silver nitrate is still used in some parts of the world.

Bacterial Conjunctivitis in Children and Adolescents

The most common causes of bacterial conjunctivitis in school-aged children are Streptococcus pneumoniae, Haemophilus species, Staphylococcus aureus, and Moraxella. The incidence of infection from
Haemophilus has decreased because of widespread immunization, whereas the incidence of methicillin-resistant S aureus (MRSA) conjunctivitis has increased. More severe forms of bacterial conjunctivitis
accompanied by copious discharge suggest infection with more virulent organisms, including N gonorrhoeae and N meningitidis.
Diagnosis is by clinical presentation. Culture to identify the o ending agent is usually not necessary in mild cases but should be performed in severe cases. If the infection is untreated, symptoms are
self-limited but may last up to 2 weeks. A broad-spectrum topical ophthalmic drop or ointment should shorten the course to a few days. Topical medications that are usually e ective include polymyxin
combinations, aminoglycosides, erythromycin, bacitracin, uoroquinolones, and azithromycin. Fluoroquinolones may be considerably more expensive than other medications and may increase the risk of
promoting drug-resistant organisms. Patients with N meningitidis conjunctivitis, and others exposed to these patients, require systemic treatment because of the high risk of meningitis.

Parinaud oculoglandular syndrome

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Kanski’s Clinical
Ophthalmology
A SYSTEMATIC APPROACH
EIGHTH EDITION

Brad Bowling
FRCSEd(Ophth), FRCOphth, FRANZCO
Ophthalmologist
Sydney
New South Wales
Australia

For additional online content visit expertconsult

S

Bowling_Title page_main.indd 3 2015-02-25 18:35:53


INTRODUCTION  132
Anatomy  132
Histology  132
Clinical features of conjunctival
inflammation  132
BACTERIAL CONJUNCTIVITIS  135
Acute bacterial conjunctivitis  135
Giant fornix syndrome  136
Adult chlamydial conjunctivitis  136
Trachoma  137
Neonatal conjunctivitis  140
VIRAL CONJUNCTIVITIS  141
ALLERGIC CONJUNCTIVITIS  144
Acute allergic conjunctivitis  144
Seasonal and perennial allergic
conjunctivitis  144
Vernal keratoconjunctivitis  145
Chapter
Conjunctiva 5  
Atopic keratoconjunctivitis  148 Parinaud oculoglandular syndrome  160
Treatment of VKC and AKC  150 Factitious conjunctivitis  160
Non-allergic eosinophilic
conjunctivitis  151
DEGENERATIONS  162
Contact allergic Pinguecula  162
blepharoconjunctivitis  151 Pterygium  162
Giant (mechanically induced) papillary Concretions  164
conjunctivitis  151 Conjunctivochalasis  165
Retention (primary epithelial inclusion)
CONJUNCTIVITIS IN BLISTERING cyst  165
MUCOCUTANEOUS DISEASE  152
Mucous membrane pemphigoid  152 SUBCONJUNCTIVAL
HAEMORRHAGE  166
Stevens–Johnson syndrome/toxic
epidermal necrolysis (Lyell
syndrome)  155
MISCELLANEOUS
CONJUNCTIVITIDES  158
Superior limbic keratoconjunctivitis  158
Ligneous conjunctivitis  160
132 Introduction
INTRODUCTION
Anatomy
The conjunctiva is a transparent mucous membrane that lines the
inner surface of the eyelids and the anterior surface of the globe,
terminating at the corneoscleral limbus. It is richly vascular, sup-
plied by the anterior ciliary and palpebral arteries. There is a dense
lymphatic network, with drainage to the preauricular and sub-
mandibular nodes corresponding to that of the eyelids. It has a
key protective role, mediating both passive and active immunity.
Anatomically, it is divided into the following:
• The palpebral conjunctiva starts at the mucocutaneous
junction of the lid margins and is firmly attached to the
posterior tarsal plates. The tarsal blood vessels are vertically
orientated.
• The forniceal conjunctiva is loose and redundant.
• The bulbar conjunctiva covers the anterior sclera and is
continuous with the corneal epithelium at the limbus. Radial
ridges at the limbus form the palisades of Vogt, the likely
reservoir of corneal stem cells. The stroma is loosely
attached to the underlying Tenon capsule, except at the
limbus, where the two layers fuse. The plica semilunaris
(semilunar fold) is present nasally, medial to which lies a
fleshy nodule (caruncle) consisting of modified cutaneous
tissue.
Histology
• The epithelium is non-keratinizing and around five cell
layers deep (Fig. 5.1). Basal cuboidal cells evolve into
flattened polyhedral cells, subsequently being shed from the
surface. Mucus-secreting goblet cells are located within the
epithelium, being most dense inferonasally and in the
fornices.
• The stroma (substantia propria) consists of richly
vascularized loose connective tissue. The accessory lacrimal
glands of Krause and Wolfring are located deep within the
stroma. Secretions from the accessory lacrimal glands are
essential components of the tear film.
Fig. 5.1  Histology of the conjunctiva
(Courtesy of J Harry)
• Conjunctiva-associated lymphoid tissue (CALT) is critical
in the initiation and regulation of ocular surface immune
responses. It consists of lymphocytes within the epithelial
layers, lymphatics and associated blood vessels, with a
stromal component of lymphocytes and plasma cells,
including follicular aggregates.
Clinical features of conjunctival
inflammation
Symptoms
Non-specific symptoms include lacrimation, grittiness, stinging
and burning. Itching is the hallmark of allergic disease, although
it may also occur to a lesser extent in blepharitis and dry eye.
Significant pain, photophobia or a marked foreign body sensation
suggest corneal involvement.
Discharge
• Watery discharge is composed of a serous exudate and
tears, and occurs in acute viral or acute allergic
conjunctivitis.
• Mucoid discharge is typical of chronic allergic conjunctivitis
and dry eye.
• Mucopurulent discharge typically occurs in chlamydial or
acute bacterial infection.
• Moderately purulent discharge occurs in acute bacterial
conjunctivitis.
• Severe purulent discharge is suggestive of gonococcal
infection.
Conjunctival reaction
• Hyperaemia that is diffuse, beefy-red and more intense away
from the limbus is usual in bacterial infection (Fig. 5.2A).
This ‘conjunctival injection’ should be distinguished from
the ciliary injection of iridocyclitis (see Ch. 11).
• Haemorrhages may occur in viral conjunctivitis, when
they are often multiple, small and discrete (‘petechial’ –
Fig. 5.2B), and severe bacterial conjunctivitis, when they are
larger and diffuse.
• Chemosis (conjunctival oedema) is seen as a translucent
swelling (Fig. 5.2C), which when severe may protrude
through the eyelids. Acute chemosis usually indicates a
hypersensitivity response (e.g. pollen), but can also occur in
severe infective conjunctivitis. Subacute or chronic chemosis
has numerous causes:
○ Local, e.g. thyroid eye disease, chronic allergic
conjunctivitis, ocular or eyelid surgery, trauma.
○ Increased systemic vascular permeability, e.g. allergic
conditions, infections including meningitis, vasculitis.
○ Increased venous pressure, e.g. superior vena cava
syndrome, right-sided heart failure.
○ Decreased plasma oncotic pressure, e.g. nephrotic
syndrome.
 5
CHAPTER
Conjunctiva 133

A B

C D

E F

Fig. 5.2  Signs of conjunctival inflammation. (A) Hyperaemia (conjunctival injection); (B) petechial haemorrhages; (C) chemosis;
(D) pseudomembrane; (E) infiltration; (F) scarring
(Courtesy of P Saine –fig. A; S Tuft – fig. B; C Barry – fig. F)

• Membranes ○ Causes include severe adenoviral conjunctivitis,

○ Pseudomembranes (Fig. 5.2D) consist of coagulated
exudate adherent to the inflamed conjunctival
epithelium. They can be peeled away leaving the
underlying epithelium intact.
○ True membranes involve the superficial layers of the
conjunctival epithelium so that attempted removal leads
to tearing. The distinction between a true membrane and
a pseudomembrane is rarely clinically helpful and both
can leave scarring following resolution.
gonococcal and some other bacterial conjunctivitides
(Streptococcus spp., Corynebacterium diphtheriae),
ligneous conjunctivitis and Stevens–Johnson syndrome.
• Infiltration represents cellular recruitment to the site of
chronic inflammation and typically accompanies a papillary
response. It is recognized by loss of detail of the normal tarsal
conjunctival vessels, especially on the upper lid (Fig. 5.2E).
• Subconjunctival cicatrization (scarring) may occur in
trachoma and other severe conjunctivitides (Fig. 5.2F).
134 Introduction

Severe scarring is associated with loss of goblet cells and
accessory lacrimal glands, and can lead to cicatricial
entropion.
• Follicles
○ Signs. Multiple, discrete, slightly elevated lesions
resembling translucent grains of rice, most prominent in
the fornices (Fig. 5.3A). Blood vessels run around or
across rather than within the lesions.
○ Histology shows a subepithelial lymphoid germinal centre
with central immature lymphocytes and mature cells
peripherally (Fig. 5.3B).
○ Causes include viral and chlamydial conjunctivitis,
Parinaud oculoglandular syndrome and hypersensitivity
to topical medications. Small follicles are a normal
finding in childhood (folliculosis), as are follicles in
the fornices and at the margin of the upper tarsal
plate in adults.
• Papillae can develop only in the palpebral conjunctiva and
in the limbal bulbar conjunctiva where it is attached to the
deeper fibrous layer.
○ Signs. In contrast to follicles, a vascular core is present.
Micropapillae form a mosaic-like pattern of elevated red
dots as a result of the central vascular channel,
macropapillae (<1 mm – Fig. 5.3C) and giant papillae
(>1 mm) develop with prolonged inflammation. Apical
infiltrate or staining with fluorescein or the presence of
mucus can be present with marked activity. Limbal
papillae have a gelatinous appearance.
○ Histology shows folds of hyperplastic conjunctival
epithelium with a fibrovascular core and subepithelial
stromal infiltration with inflammatory cells (Fig. 5.3D).
Late changes include superficial stromal hyalinization,
scarring and the formation of crypts containing goblet
cells.
○ Causes include bacterial conjunctivitis, allergic
conjunctivitis, chronic blepharitis, contact lens wear,
superior limbic keratoconjunctivitis and floppy eyelid
syndrome.
Lymphadenopathy
The most common cause of lymphadenopathy associated with
conjunctivitis is viral infection. It may also occur in chlamydial
and severe bacterial conjunctivitis (especially gonococcal), and
Parinaud oculoglandular syndrome. The preauricular site is typi-
cally affected.

A C

B D

Fig. 5.3  (A) Conjunctival follicles; (B) histology of a follicle showing two subepithelial germinal centres with immature
lymphocytes centrally and mature cells peripherally; (C) conjunctival macropapillae; (D) histology of a papilla showing folds
of hyperplastic conjunctival epithelium with a fibrovascular core and subepithelial stromal infiltration with inflammatory
cells
(Courtesy of J Harry – figs B and D)
 5
CHAPTER
Conjunctiva 135

○ Systemic symptoms may occur in patients with severe

BACTERIAL CONJUNCTIVITIS
Acute bacterial conjunctivitis
Acute bacterial conjunctivitis is a common and usually self-
• Signs are variable and depend on the severity of infection.
limiting condition caused by direct contact with infected secre-
tions. The most common isolates are Streptococcus pneumoniae,
Staphylococcus aureus, Haemophilus influenzae and Moraxella
catarrhalis. A minority of cases, usually severe, are caused by the
sexually transmitted organism Neisseria gonorrhoeae, which can
readily invade the intact corneal epithelium. Meningococcal
(Neisseria meningitidis) conjunctivitis is rare, and usually affects
children.
Diagnosis
• Symptoms
○ Acute onset of redness, grittiness, burning and discharge.
○ Involvement is usually bilateral although one eye may
become affected 1–2 days before the other.
○ On waking, the eyelids are frequently stuck together and
may be difficult to open.
conjunctivitis associated with gonococcus,
meningococcus, Chlamydia and H. influenzae. In
children, the possibility of progression to systemic
involvement should always be borne in mind.
○ Eyelid oedema and erythema (Fig. 5.4A) may occur in
severe infection, particularly gonococcal.
○ Conjunctival injection as previously described (Fig. 5.4B
and see Fig. 5.2A).
○ The discharge can initially be watery, mimicking viral
conjunctivitis, but rapidly becomes mucopurulent
(Fig. 5.4C).
○ Hyperacute purulent discharge (Fig. 5.4D) may signify
gonococcal or meningococcal conjunctivitis.
○ Superficial corneal punctate epithelial erosions are
common.
○ Peripheral corneal ulceration may occur in gonococcal
and meningococcal infection, and may rapidly progress
to perforation.
○ Lymphadenopathy is usually absent except in severe
gonococcal and meningococcal infection.

A B

C D

Fig. 5.4  Bacterial conjunctivitis. (A) Eyelid oedema and erythema in severe infection; (B) diffuse tarsal and forniceal
conjunctival hyperaemia (injection); (C) mucopurulent discharge; (D) profuse purulent discharge
136 Bacterial Conjunctivitis
• Investigations are not performed routinely but may be
indicated in the following situations:
○ In severe cases, binocular conjunctival swabs and
scrapings should be taken for urgent Gram staining,
particularly to exclude gonococcal and meningococcal
infection (Gram-negative kidney-shaped intracellular
diplococci).
○ Culture should include enriched media such as chocolate
agar or Thayer–Martin for N. gonorrhoeae.
○ Polymerase chain reaction (PCR) may be required for
less severe cases that fail to respond to treatment,
particularly to rule out the possibility of chlamydial and
viral infection.
Treatment
About 60% resolve within 5 days without treatment.
• Topical antibiotics, usually four times daily for up to a week
but sometimes more intensively, are frequently administered
to speed recovery and prevent re-infection and transmission.
There is no evidence that any particular antibiotic is more
effective. Ointments and gels provide a higher concentration
for longer periods than drops but daytime use is limited
because of blurred vision. The following antibiotics are
available:
○ Chloramphenicol, aminoglycosides (gentamicin,
neomycin, tobramycin), quinolones (ciprofloxacin,
ofloxacin, levofloxacin, lomefloxacin, gatifloxacin,
moxifloxacin, besifloxacin), macrolides (erythromycin,
azithromycin) polymyxin B, fusidic acid and bacitracin.
○ Some practitioners, particularly in the United States,
believe that chloramphenicol should not be used for
routine treatment because of a possible link with aplastic
anaemia.
○ Gonococcal and meningococcal conjunctivitis should be
treated with a quinolone, gentamicin, chloramphenicol or
bacitracin 1–2 hourly as well as systemic therapy (see below).
• Systemic antibiotics are required in the following
circumstances:
○ Gonococcal infection is usually treated with a third-
generation cephalosporin such as ceftriaxone; quinolones
and some macrolides are alternatives. It is essential to
seek advice from a microbiologist and/or genitourinary
specialist.
○ H. influenzae infection, particularly in children, is
treated with oral amoxicillin with clavulanic acid; there is
a 25% risk of developing otitis and other systemic
problems.
○ Meningococcal conjunctivitis, also particularly in
children, in whom early systemic prophylaxis may be
life-saving as up to 30% develop invasive systemic disease.
The advice of paediatric and infectious disease specialists
must be sought but if in doubt treatment with
intramuscular benzylpenicillin, ceftriaxone or cefotaxime,
or oral ciprofloxacin should not be delayed.
○ Preseptal or orbital cellulitis (see Ch. 3).
• Topical steroids may reduce scarring in membranous and
pseudomembranous conjunctivitis, although evidence for
their use is unclear.
• Irrigation to remove excessive discharge may be useful in
hyperpurulent cases.
• Contact lens wear should be discontinued until at least 48
hours after complete resolution of symptoms. Contact lenses
should not be worn whilst topical antibiotic treatment
continues.
• Risk of transmission should be reduced by hand-washing
and the avoidance of towel sharing.
• Review is unnecessary for most mild/moderate adult cases,
although patients should be cautioned to seek further advice
in the event of deterioration.
• Statutory notification of public health authorities may be
required locally for some causes.
Giant fornix syndrome
Giant fornix syndrome is an uncommon entity causing chronic
relapsing pseudomembranous purulent conjunctivitis. It is believed
to be due to retained debris in a voluminous upper fornix acting
as a focus for persistent bacterial colonization (usually S. aureus)
in an elderly patient with levator disinsertion. Large protein aggre-
gations may be visualized in the upper fornix, though double
eversion with a retractor may be necessary to identify these. Sec-
ondary corneal vascularization and lacrimal obstruction are
common. It is frequently unilateral. Treatment involves repeated
sweeping of the fornix with a cotton-tipped applicator and topical
and systemic antibiotics; intensive topical steroid may be helpful.
Surgical forniceal reconstruction may be necessary in recalcitrant
cases.
Adult chlamydial conjunctivitis
Pathogenesis
Chlamydia trachomatis (Fig. 5.5) is a species of Chlamydiae, a
phylum of bacteria that cannot replicate extracellularly and hence
depends on host cells. They exist in two principal forms: (a) a
robust infective extracellular ‘elementary body’ and (b) a fragile
intracellular replicating ‘reticular body’. Adult chlamydial (inclu-
sion) conjunctivitis is an oculogenital infection usually caused by
serovars (serological variants) D–K of C. trachomatis, and affects
5–20% of sexually active young adults in Western countries.
Transmission is by autoinoculation from genital secretions,
although eye-to-eye spread probably accounts for about 10%. The
incubation period is about a week.
Urogenital infection
• In males chlamydial infection is the most common cause of
non-gonococcal urethritis (NGU), also termed non-specific
urethritis (NSU). It should be noted that the latter term is
also sometimes used to mean urethritis in which both
gonococcal and chlamydial infection have been ruled out.

C. trachomatis
TRIC (trachoma-inclusion LGV (lymphogranuloma
conjunctivitis) agents venereum) agents
L1,L2,L3 (immunotypes)
A,B,Ba,C serovars D,E,F,G,H,I,J,K serovars
– cause trachoma – cause genital, other systemic,
and ocular disease
Fig. 5.5  Classification of Chlamydia trachomatis
Chlamydial urethritis is frequently asymptomatic in men.
C. trachomatis may also cause epididymitis, and can act as a
trigger for Reiter syndrome.
• In females chlamydial urethritis typically causes dysuria and
discharge. It may progress to pelvic inflammatory disease
(PID), carrying a risk of infertility; 5–10% of women with
PID develop perihepatitis (Fitz-Hugh–Curtis syndrome).
Diagnosis
• Symptoms consist of the subacute onset of unilateral or
bilateral redness, watering and discharge. Untreated, the
conjunctivitis becomes chronic, and though self-limiting
may persist for several months. It is important to enquire
about sexual exposure if chlamydial conjunctivitis is
suspected.
• Signs
○ Watery or mucopurulent discharge.
○ Tender preauricular lymphadenopathy.
○ Large follicles are often most prominent in the inferior
fornix (Fig. 5.6A) and may also involve the upper tarsal
conjunctiva (Fig. 5.6B).
○ Superficial punctate keratitis is common.
○ Perilimbal subepithelial corneal infiltrates (Fig. 5.6C) may
appear after 2–3 weeks.
○ Chronic cases have less prominent follicles and
commonly develop papillae.
○ Mild conjunctival scarring and superior corneal pannus
(Fig. 5.6D) are not uncommon.
• Investigations. Tarsal conjunctival scrapings are obtained
using a spatula or the blunt side of a scalpel blade.
○ Nucleic acid amplification tests such as PCR are likely to
be the investigation of choice in time but validation for
ocular specimens is limited at present.
○ Giemsa staining for basophilic intracytoplasmic bodies is
performed by applying scrapings onto a glass slide.
5
CHAPTER
Conjunctiva 137
○ Direct immunofluorescence detects free elementary
bodies with about 90% sensitivity and specificity.
○ Enzyme immunoassay for direct antigen detection is also
useful.
○ McCoy cell culture is highly specific.
○ Swabs can be taken for bacterial culture, and serology
may be helpful in selected cases.
Treatment
Empirical treatment may be given if the clinical picture is convinc-
ing pending investigation results, or if investigations are negative.
• Referral to a genitourinary specialist is mandatory in
confirmed cases, particularly for the exclusion of other
sexually transmitted infections, contact tracing and
pregnancy testing.
• Systemic therapy involves one of the following:
○ Azithromycin 1 g repeated after 1 week is generally the
treatment of choice, although a second or a third course
is required in up to 30% of cases. Some guidelines
advocate only a single 1 g dose.
○ Doxycycline 100 mg twice daily for 10 days (tetracyclines
are relatively contraindicated in pregnancy/breastfeeding
and in children under 12 years of age).
○ Erythromycin, amoxicillin and ciprofloxacin are
alternatives.
• Topical antibiotics such as erythromycin or tetracycline
ointment are sometimes used to achieve rapid relief of
ocular symptoms, but are insufficient alone.
• Reduction of transmission risk involves abstinence from
sexual contact until completion of treatment (1 week after
azithromycin), together with other precautions as for any
infectious conjunctivitis.
• Re-testing for persistent infection should take place 6–12
weeks after treatment.
It is important to be aware that symptoms commonly take weeks
to settle, and that follicles and corneal infiltrates can take months
to resolve due to a prolonged hypersensitivity response to chlamy-
dial antigen.
Trachoma
Pathogenesis
Trachoma is the leading cause of preventable irreversible blind-
ness in the world. It is related to poverty, overcrowding and poor
hygiene, the morbidity being a consequence of the establishment
of re-infection cycles within communities. Whereas an isolated
episode of trachomatous conjunctivitis may be relatively innocu-
ous, recurrent infection elicits a chronic immune response con-
sisting of a cell-mediated delayed hypersensitivity (Type IV)
reaction to the intermittent presence of chlamydial antigen and
can lead to loss of sight. Prior contact with the organism confers
short-term partial immunity but also leads to a heightened inflam-
matory reaction upon reinfection. Vaccination has an effect
similar to primary infection in sensitizing the individual, and so
138 Bacterial Conjunctivitis

A B

C D

Fig. 5.6  Adult chlamydial conjunctivitis. (A) Large forniceal follicles; (B) superior tarsal follicles; (C) peripheral corneal
infiltrates; (D) superior pannus

is not helpful. The family childcare group is the most important

re-infection reservoir, and consequently young children are par-
ticularly vulnerable. The fly is an important vector, but there may
be direct transmission from eye or nasal discharge. Trachoma is
associated principally with infection by serovars A, B, Ba and C of
Chlamydia trachomatis, but the serovars D–K conventionally asso-
ciated with adult inclusion conjunctivitis, and other species of the
Chlamydiaceae family such as Chlamydophila psittaci and Chlamy-
dophila pneumoniae have also been implicated.
Diagnosis
Features of trachoma are divided into an ‘active’ inflammatory
stage and a ‘cicatricial’ chronic stage, with considerable overlap. A
World Health Organization (WHO) grading system is in use
(Table 5.1).
• Active trachoma is most common in pre-school children
and is characterized by the following:
○ Mixed follicular/papillary conjunctivitis (Fig. 5.7A)
associated with a mucopurulent discharge. In children
under the age of 2 years the papillary component may
predominate.
Table 5.1  WHO grading of trachoma
TF = trachomatous inflammation (follicular): five or more
follicles (>0.5 mm) on the superior tarsal plate
TI = trachomatous inflammation (intense): diffuse
involvement of the tarsal conjunctiva, obscuring 50% or
more of the normal deep tarsal vessels; papillae are
present
TS = trachomatous conjunctival scarring: easily visible
fibrous white tarsal bands
TT = trachomatous trichiasis: at least one lash touching
the globe
CO = corneal opacity sufficient to blur details of at least
part of the pupillary margin
○ Superior epithelial keratitis and pannus formation
(Fig. 5.7B).
• Cicatricial trachoma is prevalent in middle age.
○ Linear or stellate (Fig. 5.7C) conjunctival scars in mild
cases, or broad confluent scars (Arlt line – Fig. 5.7D) in
severe disease.
 5
CHAPTER
Conjunctiva 139

A B

C D

E F

Fig. 5.7  Trachoma. (A) Typical white subtarsal follicles; (B) marked pannus; (C) stellate conjunctival scarring; (D) Arlt’s line and
conjunctival follicles; (E) Herbert pits; (F) cicatricial entropion
(Courtesy of C Barry – figs A, B, D–F)

○ Although the entire conjunctiva is involved, the effects
are most prominent on the upper tarsal plate.
○ Superior limbal follicles may resolve to leave a row of
shallow depressions (Herbert pits – Fig. 5.7E).
○ Trichiasis, distichiasis, corneal vascularization and
cicatricial entropion (Fig. 5.7F).
○ Severe corneal opacification.
○ Dry eye caused by destruction of goblet cells and the
ductules of the lacrimal gland.
• Investigations are rarely used in the affected areas, diagnosis
being made on clinical features in most cases. Various field
techniques (e.g. dipstick enzyme immunoassay) are available
and investigations otherwise are similar to those for adult
inclusion conjunctivitis.
140 Bacterial Conjunctivitis
Management
The SAFE strategy for trachoma management supported by the
WHO and other agencies encompasses Surgery for trichiasis, Anti-
biotics for active disease, Facial hygiene and Environmental
improvement.
• Antibiotics should be administered to those affected and to
all family members. A single antibiotic course is not always
effective in eliminating infection in an individual, and
communities may need to receive annual treatment to
suppress infection.
○ A single dose of azithromycin (20 mg/kg up to 1 g) is the
treatment of choice.
○ Erythromycin 500 mg twice daily for 14 days or
doxycycline 100 mg twice daily for 10 days (tetracyclines
are relatively contraindicated in pregnancy/breastfeeding
and in children under 12).
○ Topical 1% tetracycline ointment is less effective than oral
treatment.
• Facial cleanliness is a critical preventative measure.
• Environmental improvement, such as access to adequate
water and sanitation, as well as control of flies, is important.
• Surgery is aimed at relieving entropion and trichiasis and
maintaining complete lid closure, principally with bilamellar
tarsal rotation.
Neonatal conjunctivitis
Neonatal conjunctivitis (ophthalmia neonatorum) is defined as
conjunctival inflammation developing within the first month of
life. It is the most common infection of any kind in neonates,
occurring in up to 10%. It is identified as a specific entity distinct
from conjunctivitis in older infants because of its potentially
serious nature (both ocular and systemic complications) and
because it is often the result of infection transmitted from mother
to infant during delivery.
Causes
• Organisms acquired during vaginal delivery:
C. trachomatis, N. gonorrhoeae (now rare in wealthier
countries, but previously responsible for 25% of childhood
blindness) and herpes simplex virus (HSV, typically HSV-2).
With all of these, conjunctivitis is not uncommonly
associated with severe ocular or systemic complications.
C. trachomatis is the most common cause in cases involving
moderate to severe conjunctival inflammation.
• Staphylococci are usually responsible for mild
conjunctivitis; other bacterial causes include streptococci,
H. influenzae and various Gram-negative organisms.
• Topical preparations used as prophylaxis against infection
(see below), may themselves cause conjunctival irritation
(chemical conjunctivitis).
• Congenital nasolacrimal obstruction. Despite poor
neonatal tear production, a persistently mildly watery eye
with recurrent mild bacterial conjunctivitis may be
secondary to an as yet uncanalized tear duct.
Diagnosis
• Timing of onset
○ Chemical irritation: first few days.
○ Gonococcal: first week.
○ Staphylococci and other bacteria: end of the first week.
○ HSV: 1–2 weeks.
○ Chlamydia: 1–3 weeks.
• History
○ Instillation of a prophylactic chemical preparation.
○ Parental symptoms of sexually transmitted infection
(STI).
○ Recent conjunctivitis in close contacts.
○ Features of systemic illness in the child: pneumonitis,
rhinitis and otitis in chlamydial infection, skin vesicles
and features of encephalitis in HSV; disseminated
gonococcal infection is relatively rare.
○ Prior persistent watering without inflammation may
indicate an uncanalized nasolacrimal duct.
• Signs
○ A mildly sticky eye may occur in staphylococcal infection,
or with delayed nasolacrimal duct canalization
(mucopurulent reflux on pressure over the lacrimal sac).
○ Discharge is characteristically watery in chemical and
HSV infection, mucopurulent in chlamydial infection,
purulent (Fig. 5.8) in bacterial infection, and
hyperpurulent in gonococcal conjunctivitis.
○ Severe eyelid oedema occurs in gonococcal infection; it
may be difficult to distinguish severe conjunctivitis from
preseptal or orbital infection. Signs of dacrocystitis
should be excluded.
○ Eyelid and periocular vesicles may occur in HSV
infection, and can critically aid early diagnosis and
treatment.
Fig. 5.8  Eyelid oedema and purulent discharge in neonatal
conjunctivitis

○ Corneal examination is mandatory, and is particularly
important if gonococcal infection is suspected, as
ulceration with rapid progression is common. Use of a
pen torch, insertion of an eyelid speculum and
fluorescein drops may be helpful; the latter may facilitate
identification of a dendritic or geographic epithelial
lesion that may be present in HSV infection (in contrast
to the punctate epitheliopathy seen in older children with
primary herpetic conjunctivitis).
○ Pseudomembranes are not uncommon in chlamydial
conjunctivitis.
○ Congenital glaucoma may masquerade as neonatal
conjunctivitis and should always be considered,
particularly in monocular cases.
• Investigations are tailored to the clinical picture:
○ The results of any parental prenatal testing for STI should
be obtained.
○ Conjunctival scrapings are taken for nucleic acid
amplification (PCR), particularly for Chlamydia
and HSV.
○ Separate conjunctival scrapings are applied to a glass
slide for Gram and Giemsa staining. Multinucleated
giant cells may be present on Gram stain in HSV
infection.
○ Conjunctival swabs are taken with a calcium alginate
swab or a sterile cotton-tipped applicator, for standard
bacterial culture and chocolate agar or Thayer–Martin
(for N. gonorrhoeae).
○ Epithelial cells infected with HSV may show eosinophilic
intranuclear inclusions on Papanicolaou smear.
○ Conjunctival scrapings or fluid from skin vesicles can be
sent for viral culture for HSV.
○ Specimens should be taken prior to fluorescein
instillation if immunofluorescent testing is planned.
Treatment
• Prophylaxis is routinely performed but there is no standard
protocol.
○ A single instillation of povidone-iodine 2.5% solution is
effective against common pathogens.
○ Erythromycin 0.5% or tetracycline 1% ointment.
○ Silver nitrate 1% solution agglutinates gonococci and is
still utilized in areas where gonococcal infection is
common. It should be administered in conjunction with
a single intramuscular dose of benzylpenicillin when
maternal infection is present.
• Chemical conjunctivitis does not require treatment apart
from artificial tears.
• Mild conjunctivitis. A mildly sticky eye is extremely
common in neonates. Investigation is often unnecessary and
a low-intensity regimen with a broad-spectrum topical
antibiotic such as chloramphenicol, erythromycin or fusidic
acid ointment is adequate in most cases. Further
investigation and treatment can be instituted if the condition
fails to settle.
5
CHAPTER
Conjunctiva 141
• Moderate to severe cases should be investigated as above;
microscopy with Gram staining alone is highly sensitive and
will often provide a working diagnosis.
○ If the diagnosis is uncertain but chlamydial infection is a
reasonable possibility, oral erythromycin can be
commenced on an empirical basis after samples have
been collected.
○ If bacteria are evident on Gram stain, a broad-spectrum
topical antibiotic (e.g. chloramphenicol, erythromycin
or bacitracin for Gram-positive organisms, neomycin,
ofloxacin or gentamicin for Gram-negatives) should be
used until sensitivities are available; additional systemic
treatment should be considered in more severe cases.
• Severe conjunctivitis, or when systemic illness is suspected,
requires hospital admission. Samples should be taken for a
range of investigations, including urgent microscopy, and a
broad-spectrum topical antibiotic, such as erythromycin,
commenced. The ocular risk is usually most acute from
gonococcal infection, so empirical topical treatment should
cover this, and in most cases consideration given to systemic
treatment such as parenteral ceftriaxone.
• Chlamydial infection is treated with oral erythromycin for 2
weeks; a longer or supplementary course may be needed.
Erythromycin or tetracycline ointment can be used in
addition, but is probably unnecessary.
• Gonococcal conjunctivitis is treated systemically with a
third-generation cephalosporin and often with
supplementary topical treatment. Co-treatment for
Chlamydia is prudent. Saline irrigation to remove excessive
discharge should be considered.
• Herpes simplex infection should always be regarded
as a systemic condition and is treated with high-dose
intravenous aciclovir under paediatric specialist care. Early
diagnosis and treatment of encephalitis (PCR of
cerebrospinal fluid (CSF) is positive in 95%) may be
life-saving or prevent serious neurological disability. Topical
aciclovir may be considered in addition.
• Microbiological advice should be sought in severe cases,
especially regarding local antibiotic sensitivities.
• Paediatric specialist involvement is mandatory when
systemic disease may be present.
• Genitourinary referral for the mother and her sexual
contacts is important when an STI is diagnosed. The neonate
should be screened for other STIs.
• Notification of a case of neonatal conjunctivitis to the local
public health authority is a statutory requirement in many
countries.
VIRAL CONJUNCTIVITIS
Introduction
Viral conjunctivitis is a common external ocular infection, adeno-
virus (a non-enveloped double-stranded DNA virus) being the
most frequent (90%) causative agent. It may be sporadic, or
occur in epidemics in environments such as workplaces (including
142 Viral Conjunctivitis
hospitals), schools and swimming pools. The spread of this
highly contagious infection is facilitated by the ability of viral
particles to survive on dry surfaces for weeks, and by the fact that
viral shedding may occur for many days before clinical features
are apparent. Transmission is generally by contact with respiratory
or ocular secretions, including via fomites such as contaminated
towels.
Presentation
The spectrum of viral conjunctivitis varies from mild subclinical
disease to severe inflammation with significant morbidity.
There will often be a history of a close contact with acute
conjunctivitis.
• Non-specific acute follicular conjunctivitis is the most
common clinical form of viral conjunctivitis, and is typically
due to adenoviral infection by a range of serological variants.
Unilateral watering, redness, irritation and/or itching, and
mild photophobia occur, the contralateral eye generally
being affected 1–2 days later, often less severely. The
condition is usually milder than the other clinical forms of
adenoviral conjunctivitis; patients may have accompanying
(usually mild) systemic symptoms, such as a sore throat
or common cold.
• Pharyngoconjunctival fever (PCF) is caused mainly by
adenovirus serovars 3, 4 and 7. It is spread by droplets
within families with upper respiratory tract infection.
Keratitis develops in about 30% of cases but is seldom
severe. Symptoms are essentially as above, though sore
throat is typically prominent.
• Epidemic keratoconjunctivitis (EKC) is caused mainly by
adenovirus serovars 8, 19 and 37, and is the most severe
ocular adenoviral infection. Keratitis, which may be marked,
develops in about 80%; photophobia may be
correspondingly prominent.
• Acute haemorrhagic conjunctivitis usually occurs in
tropical areas. It is typically caused by enterovirus and
coxsackievirus, though other microorganisms may present
similarly. It has a rapid onset, and resolves within 1–2 weeks.
Conjunctival haemorrhage is generally marked.
• Chronic/relapsing adenoviral conjunctivitis giving a
chronic non-specific follicular/papillary clinical picture can
persist over years, but is rare and eventually self-limiting.
• Herpes simplex virus (HSV) can cause a follicular
conjunctivitis, particularly in primary infection; this is
usually unilateral and there are often associated skin vesicles.
• Systemic viral infections such as those common in
childhood, e.g. varicella, measles and mumps, can feature an
associated follicular conjunctivitis; varicella-zoster virus
secondary infection commonly causes a conjunctivitis as
part of ophthalmic shingles. An HIV conjunctivitis is
recognized.
• Molluscum contagiosum is a skin infection caused by a
human specific double-stranded DNA poxvirus that typically
affects otherwise healthy children, with a peak incidence
between the ages of 2 and 4 years. Transmission is by
contact, with subsequent autoinoculation. A chronic
follicular conjunctivitis can be associated, and is due to skin
lesion shedding of viral particles. Chronic unilateral ocular
irritation and mild discharge is typical. The eyelash line
should be examined carefully in patients with chronic
conjunctivitis so as not to overlook a molluscum lesion.
Signs
• Eyelid oedema ranges from negligible to severe.
• Lymphadenopathy is common: tender pre-auricular.
• Conjunctival hyperaemia and follicles (Fig. 5.9A) are
typically prominent; papillae may also be seen, particularly
in the superior tarsal conjunctiva.
• Severe inflammation may be associated with conjunctival
haemorrhages (usually petechial in adenoviral infection – see
Fig. 5.2B), chemosis, membranes (rare) and
pseudomembranes (Fig. 5.9B), sometimes with conjunctival
scarring after resolution (Fig. 5.9C).
• Keratitis (adenoviral):
○ Epithelial microcysts (non-staining) are common at an
early stage.
○ Punctate epithelial keratitis (staining) may occur, usually
within 7–10 days of the onset of symptoms, typically
resolving within 2 weeks.
○ Focal white subepithelial/anterior stromal infiltrates
(Fig. 5.9D) often develop beneath the fading epithelial
lesions, probably as an immune response to the virus;
they may persist or recur over months or years.
○ Small pseudodendritic epithelial formations sometimes
occur.
• Anterior uveitis is sometimes present, but is mild.
• Molluscum contagiosum.
○ A pale, waxy, umbilicated nodule on the lid margin
(Fig. 5.10A) associated with follicular conjunctivitis
(Fig. 5.10B) and mild watery and mucoid discharge.
○ Bulbar nodules and confluent cutaneous lesions may
occur in immunocompromised patients.
Investigation
Investigation is generally unnecessary, but should be considered if
the diagnosis is in doubt or there is failure of resolution.
• Giemsa stain shows predominantly mononuclear cells in
adenoviral conjunctivitis and multinucleated giant cells in
herpetic infection.
• Nucleic acid amplification techniques such as PCR are
sensitive and specific for viral DNA.
• Viral culture with isolation is the reference standard but is
expensive and fairly slow (days to weeks), and requires
specific transport media. Sensitivity is variable but specificity
is around 100%.
• A ‘point-of-care’ immunochromatography test takes 10
minutes to detect adenoviral antigen in tears; sensitivity and
specificity are excellent.
• Serology for IgM or rising IgG antibody titres to adenovirus
has limitations and is rarely used.
 5
CHAPTER
Conjunctiva 143

A B

C D

Fig. 5.9  Adenoviral keratoconjunctivitis. (A) Follicular conjunctivitis; (B) pseudomembrane; (C) residual scarring;
(D) subepithelial infiltrates
(Courtesy of S Tuft – figs B and C)

• Investigation for other causes such as chlamydial infection
may be indicated in non-resolving cases.
Treatment
The treatment of herpetic ocular surface disease is addressed in
Chapter 6.
• Spontaneous resolution of adenoviral infection usually
occurs within 2–3 weeks, so specific treatment is typically
unnecessary. No antiviral agent with clinically useful activity
against adenovirus has yet been produced.
• Reduction of transmission risk by meticulous hand hygiene,
avoiding eye rubbing and towel sharing. There should be
scrupulous disinfection of instruments and clinical surfaces
after examination of an infected patient (e.g. sodium
hypochlorite, povidone-iodine).
• Molluscum contagiosum. Although lesions are self-limiting
in immunocompetent patients, removal is often necessary to

A B

Fig. 5.10  (A) Molluscum eyelid lesion; (B) follicular conjunctivitis associated with a molluscum lesion
144 Allergic Conjunctivitis

address secondary conjunctivitis or for cosmetic reasons. settles within hours as the acute increase in vascular permeability
Expression is facilitated by making a small nick in the skin at resolves. Cool compresses can be used and a single drop of adrena-
the margin of the lesion with the tip of a needle. line 0.1% may reduce extreme chemosis.
• Topical steroids such as prednisolone 0.5% four times daily
may be required for severe membranous or
pseudomembranous adenoviral conjunctivitis. Symptomatic
Seasonal and perennial  
keratitis may require weak topical steroids but these should allergic conjunctivitis
be used with caution as they do not speed resolution but These common subacute conditions are distinguished from each
only suppress inflammation, and lesions commonly recur other by the timing of exacerbations, thought to relate principally
after premature discontinuation. Steroids may enhance viral to differing stimulating allergens in each.
replication and extend the period during which the patient • Seasonal allergic conjunctivitis (‘hay fever eyes’), worse
remains infectious. Intraocular pressure should be during the spring and summer, is the more common. The
monitored if treatment is prolonged. most frequent allergens are tree and grass pollens, although
• Other measures the specific allergen varies with geographic location.
○ Discontinuation of contact lens wear until resolution of
• Perennial allergic conjunctivitis causes symptoms
symptoms. throughout the year, generally worse in the autumn when
○ Artificial tears four times daily may be useful for exposure to house dust mites, animal dander and fungal
symptomatic relief. Preservative-free preparations may
give superior comfort, and if supplied in single-dose units
may reduce transmission risk.
○ Cold (or warm) compresses for symptomatic relief.
○ Topical antihistamines and vasoconstrictors may improve
symptoms, particularly itching.
○ The place of non-steroidal anti-inflammatory drops is
not well established, but may be effective in some
circumstances such as steroid weaning. They are not
thought to promote viral replication.
○ Removal of symptomatic pseudomembranes or
membranes.
○ Topical antibiotics if secondary bacterial infection is
suspected.
○ Povidone-iodine is very effective against free (although
less so against intracellular) adenovirus, and has been
proposed as a means of decreasing infectivity.
A

ALLERGIC CONJUNCTIVITIS
Atopy is a genetically determined predisposition to hypersensitiv-
ity reactions upon exposure to specific environmental antigens.
Clinical manifestations include the various forms of allergic con-
junctivitis, as well as hay fever (seasonal allergic rhinitis), asthma
and eczema. Allergic conjunctivitis is a Type I (immediate) hyper-
sensitivity reaction, mediated by degranulation of mast cells in
response to the action of IgE; there is evidence of an element of
Type IV hypersensitivity in at least some forms.

Acute allergic conjunctivitis

Acute allergic conjunctivitis is a common condition caused by
an acute conjunctival reaction to an environmental allergen,
usually pollen. It is typically seen in younger children after playing
outside in spring or summer. Acute itching and watering are B
common, but the hallmark is chemosis (Figs 5.11A and B), which
is frequently dramatic and worrying to the child and parents. Fig. 5.11  (A) Mild and (B) severe chemosis in acute allergic
Treatment is not usually required and the conjunctival swelling conjunctivitis

allergens is greatest. It is less common and tends to be
milder than the seasonal form.
Diagnosis
• Symptoms. Transient acute or subacute attacks of redness,
watering and itching, associated with sneezing and nasal
discharge.
• Signs. Conjunctival hyperaemia with a relatively mild
papillary reaction, variable chemosis and lid oedema.
• Investigations are generally not performed although
conjunctival scraping in more active cases may demonstrate
the presence of eosinophils. Skin testing for particular
allergens is rarely required.
Treatment
• Artificial tears for mild symptoms.
• Mast cell stabilizers (e.g. sodium cromoglicate, nedocromil
sodium, lodoxamide) must be used for a few days before
exerting maximal effect, but are suitable (except
lodoxamide) for long-term use if required.
• Antihistamines (e.g. emedastine, epinastine, levocabastine,
bepotastine) can be used for symptomatic exacerbations and
are as effective as mast cell stabilizers.
• Dual action antihistamine and mast cell stabilizers (e.g.
azelastine, ketotifen, olopatadine) act rapidly and are often
very effective for exacerbations.
• Combined preparation of an antihistamine and a
vasoconstrictor (e.g. antazoline with xylometazoline).
• Non-steroidal anti-inflammatory preparations (e.g.
diclofenac) can provide symptomatic relief but are rarely
used.
• Topical steroids are effective but rarely necessary.
• Oral antihistamines may be indicated for severe symptoms.
Some, such as diphenhydramine, cause significant
drowsiness and may be useful in aiding sleep; others, such as
loratadine, have a far less marked sedative action.
Vernal keratoconjunctivitis
Pathogenesis
Vernal keratoconjunctivitis (VKC) is a recurrent bilateral disorder
in which both IgE- and cell-mediated immune mechanisms play
important roles. It primarily affects boys and onset is generally
from about the age of 5 years onwards. There is remission by the
late teens in 95% of cases, although many of the remainder develop
atopic keratoconjunctivitis. VKC is rare in temperate regions but
relatively common in warm dry climates such as the Mediter­
ranean, sub-Saharan Africa and the Middle East. In temperate
regions over 90% of patients have other atopic conditions such as
asthma and eczema and two-thirds have a family history of atopy.
VKC often occurs on a seasonal basis, with a peak incidence over
late spring and summer, although there may be mild perennial
symptoms.
5
CHAPTER
Conjunctiva 145
Classification
• Palpebral VKC primarily involves the upper tarsal
conjunctiva. It may be associated with significant corneal
disease as a result of the close apposition between the
inflamed conjunctiva and the corneal epithelium.
• Limbal disease typically affects black and Asian patients.
• Mixed VKC has features of both palpebral and limbal
disease.
Diagnosis
The diagnosis is clinical; investigations are generally not indicated.
Eosinophils may be abundant in conjunctival scrapings.
• Symptoms consist of intense itching, which may be
associated with lacrimation, photophobia, a foreign body
sensation, burning and thick mucoid discharge. Increased
blinking is common.
• Palpebral disease
○ Early-mild disease is characterized by conjunctival
hyperaemia and diffuse velvety papillary hypertrophy on
the superior tarsal plate (Fig. 5.12A).
○ Macropapillae (<1 mm) have a flat-topped polygonal
appearance reminiscent of cobblestones; focal (Fig. 5.12B)
or diffuse (Fig. 5.12C) whitish inflammatory infiltrates
may be seen in intense disease.
○ Progression to giant papillae (>1 mm) can occur, as
adjacent smaller lesions amalgamate when dividing septa
rupture (Fig. 5.12D).
○ Mucus deposition between giant papillae (Fig. 5.12E).
○ Decreased disease activity is characterized by milder
conjunctival injection and decreased mucus production
(Fig. 5.12F).
• Limbal disease
○ Gelatinous limbal conjunctival papillae that may be
associated with transient apically located white cellular
collections (Horner–Trantas dots – Fig. 5.13A–C).
○ In tropical regions, limbal disease may be severe
(Fig. 5.13D).
• Keratopathy is more frequent in palpebral disease and may
take the following forms:
○ Superior punctate epithelial erosions associated
with layers of mucus on the superior cornea
(Fig. 5.14A).
○ Epithelial macroerosions caused by a combination of
epithelial toxicity from inflammatory mediators and a
direct mechanical effect from papillae (Fig. 5.14B–D).
○ Plaques and ‘shield’ ulcers (Fig. 5.15A and B) may develop
in palpebral or mixed disease when the exposed Bowman
membrane becomes coated with mucus and calcium
phosphate, leading to inadequate wetting and delayed
re-epithelialization. This development is serious and
warrants urgent attention to prevent secondary bacterial
infection.
○ Subepithelial scars that are typically grey and oval
(Fig. 5.15C), and may affect vision.
146 Allergic Conjunctivitis

A B

C D

E F

Fig. 5.12  Palpebral vernal disease. (A) Diffuse fine papillary hypertrophy; (B) macropapillae with focal inflammatory infiltrates;
(C) macropapillae with diffuse infiltrate; (D) giant papillae; (E) intense disease with mucus; (F) milder disease; note mucous
discharge
(Courtesy of S Tuft – fig. D)
 A B

C D

Fig. 5.13  Limbal vernal disease. (A) Sparse limbal papillae; (B) papillae with Horner–Trantas dots; (C) extensive papillae;
(D) severe features
(Courtesy of S Tuft – fig. B)

A B

C D

Fig. 5.14  Keratopathy in vernal disease. (A) Superior punctate erosions and mucus stained with rose Bengal; (B–D) gradual
resolution of a macroerosion over months of treatment
(Courtesy of S Tuft – fig. A)
148 Allergic Conjunctivitis

A B

C D

Fig. 5.15  Keratopathy in vernal disease. (A) Early plaque; (B) plaque and shield ulcer; (C) subepithelial scarring following
ulceration; (D) pseudogerontoxon and limbal papillae
(Courtesy of S Tuft – figs A and D)

○ Pseudogerontoxon can develop in recurrent limbal Atopic keratoconjunctivitis

disease. It is characterized by a paralimbal band of
superficial scarring resembling arcus senilis (Fig. 5.15D),
adjacent to a previously inflamed segment of the limbus.
○ Vascularization does not tend to be prominent, though
some peripheral superficial vessel ingrowth is common,
especially superiorly.
○ Keratoconus and other forms of corneal ectasia are more
common in VKC and are thought to be at least partly
due to persistent eye rubbing.
○ Herpes simplex keratitis is more common than average,
though less so than in atopic keratoconjunctivitis. It can
be aggressive and is occasionally bilateral.
• Eyelid disease is usually mild, in contrast to atopic
keratoconjunctivitis.
Pathogenesis
Atopic keratoconjunctivitis (AKC) is a rare bilateral disease that
typically develops in adulthood (peak incidence 30–50 years) fol-
lowing a long history of atopic dermatitis (eczema); asthma is also
extremely common in these patients. About 5% have suffered
from childhood VKC. There is little or no gender preponderance.
AKC tends to be chronic and unremitting, with a relatively low
expectation of eventual resolution, and is associated with signifi-
cant visual morbidity. Whereas VKC is more frequently seasonal
and generally worse in the spring, AKC tends to be perennial and
is often worse in the winter. Patients are sensitive to a wide range
of airborne environmental allergens.
 5
CHAPTER
Conjunctiva 149

A B

C D

E F

Fig. 5.16  Atopic disease. (A) Severe eyelid involvement; (B) infiltration and scarring of the tarsal conjunctiva; (C) forniceal
shortening; (D) keratinization of the caruncle; (E) dense punctate epithelial erosions; (F) persistent epithelial defect and
peripheral corneal vascularization; a penetrating keratoplasty interface can be seen
(Courtesy of S Tuft)

scaliness and thickening, sometimes with disruption to

Diagnosis
The distinction between AKC and VKC is essentially clinical; eosi-
nophils tend to be less common in conjunctival scrapings than
with VKC.
• Symptoms are similar to those of VKC, but are frequently
more severe and unremitting.
• Eyelids
○ Skin changes (Fig. 5.16A) are more prominent than in
VKC, and are typically eczematoid: erythema, dryness,
epidermal integrity such as fissuring and scratches
(excoriation), the latter due to intense itching.
○ Associated chronic staphylococcal blepharitis and
madarosis are common.
○ There may be keratinization of the lid margin.
○ Hertoghe sign: absence of the lateral portion of the
eyebrows.
○ Dennie–Morgan folds: lid skin folds caused by persistent
rubbing.
150 Allergic Conjunctivitis
○ Tightening of the facial skin may cause lower lid
ectropion and epiphora.
○ Ptosis is not uncommon.
• Conjunctival involvement is preferentially inferior
palpebral, whereas in VKC it is worse superiorly.
○ Discharge is generally more watery than the stringy
mucoid discharge in VKC.
○ Hyperaemia; chemosis is not uncommon during active
inflammation.
○ Papillae are initially smaller than in VKC although larger
lesions may develop later.
○ Diffuse conjunctival infiltration and scarring may give a
whitish, featureless appearance (Fig. 5.16B).
○ Cicatricial changes can lead to moderate symblepharon
formation, forniceal shortening (Fig. 5.16C) and
keratinization of the caruncle (Fig. 5.16D).
○ Limbal involvement similar to that of limbal VKC can be
seen, including Horner–Trantas dots.
• Keratopathy
○ Punctate epithelial erosions over the inferior third of the
cornea are common and can be marked (Fig. 5.16E).
○ Persistent epithelial defects (Fig. 5.16F), sometimes with
associated focal thinning, can occasionally progress to
perforation with descemetocoele (US spelling –
descemetocele) formation.
○ Plaque formation may occur (see Figs 5.15A and B).
○ Peripheral vascularization and stromal scarring are more
common than in VKC.
○ Predisposition to secondary bacterial and fungal
infection, and to aggressive herpes simplex keratitis.
○ Keratoconus is common (about 15%) and as with VKC
may be secondary to chronic ocular rubbing.
• Cataract
○ Presenile shield-like anterior or posterior subcapsular
cataracts are common and may be exacerbated by
long-term steroid therapy.
○ Because of the high lid margin carriage of S. aureus,
cataract surgery carries an increased risk of
endophthalmitis.
• Retinal detachment is more common than in the general
population, and is a particular risk following cataract surgery.
Treatment of VKC and AKC
The management of VKC does not differ substantially from that
of AKC, although the latter is generally less responsive and requires
more intensive and prolonged treatment.
General measures
• Allergen avoidance, if possible. An allergy specialist opinion
may be requested; allergen (e.g. patch) testing is sometimes
useful, but often gives non-specific results.
• Cool compresses may be helpful.
• Lid hygiene should be used for associated staphylococcal
blepharitis. Moisturizing cream such as E45 can be applied
to dry, fissured skin.
• Bandage contact lens wear to aid healing of persistent
epithelial defects.
Local treatment
• Mast cell stabilizers (e.g. sodium cromoglicate, nedocromil
sodium, lodoxamide) reduce the frequency of acute
exacerbations and the need for steroids and so form the
basis of many regimens, but are seldom effective in isolation.
Several days to weeks of treatment are needed for a
reasonable response and long-term therapy may be needed
(lodoxamide is not licensed for long-term use).
• Topical antihistamines (e.g. emedastine, epinastine,
levocabastine, bepotastine) when used in isolation are about
as effective as mast cell stabilizers. They are suitable for acute
exacerbations but generally not for continuous long-term
use, and courses of several preparations are licensed for use
only in courses of limited duration. A trial of several
different agents may be worthwhile.
• Combined antihistamine and vasoconstrictor (e.g.
antazoline with xylometazoline) may offer relief in some
cases.
• Combined action antihistamine/mast cell stabilizers (e.g.
azelastine, ketotifen, olopatadine) are helpful in many
patients and have a relatively rapid onset of action.
• Non-steroidal anti-inflammatory preparations (e.g.
ketorolac, diclofenac) may improve comfort by blocking
non-histamine mediators. Combining one of these with
a mast cell stabilizer is an effective regimen in some
patients.
• Topical steroids (e.g. fluorometholone 0.1%, rimexolone
1%, prednisolone 0.5%, loteprednol etabonate 0.2% or 0.5%)
are used for (a) severe exacerbations of conjunctivitis and
(b) significant keratopathy; reducing conjunctival activity
generally leads to corneal improvement. They are usually
prescribed in short but intensive (e.g. 2-hourly initially)
courses, aiming for very prompt tapering. Although the risk
of elevation of intraocular pressure is low, monitoring is
advisable if long-term treatment is necessary. Stronger
preparations such as prednisolone 1% can be used but carry
a higher risk of steroid-induced glaucoma.
• Steroid ointment (e.g. hydrocortisone 0.5%) may be used to
treat the eyelids in AKC, though as with eye drops, the
duration of treatment should be minimized and the
intraocular pressure (IOP) monitored.
• Antibiotics may be used in conjunction with steroids in
severe keratopathy to prevent or treat bacterial infection.
• Acetylcysteine is a mucolytic agent that is useful in VKC for
dissolving mucus filaments and deposits, and addressing
early plaque formation.
• Immune modulators
○ Ciclosporin (0.05–2% between two and six times daily)
may be indicated if steroids are ineffective, inadequate or
poorly tolerated, or as a steroid-sparing agent in patients
with severe disease. The effects typically take some weeks
to be exerted, and relapses may occur if treatment is

stopped suddenly. Irritation and blurred vision are
common.
○ Calcineurin inhibitors show increasing promise as an
alternative to steroids in the treatment of allergic eye
disease. Tacrolimus 0.03% ointment can be effective in
AKC for severe eyelid disease. Instillation into the
fornices has been effective in modulating conjunctival
inflammation in refractory cases.
• Supratarsal steroid injection may be considered in severe
palpebral disease or for non-compliant patients. The
injection is given into the conjunctival surface of the
anaesthetized everted upper eyelid; 0.1 ml of betamethasone
sodium phosphate 4 mg/ml, dexamethasone 4 mg/ml or
triamcinolone 40 mg/ml is given.
Systemic treatment
• Oral antihistamines help itching, promote sleep and reduce
nocturnal eye rubbing. Because other inflammatory
mediators are involved besides histamines, effectiveness is
not assured. Some antihistamines (e.g. loratadine) cause
relatively little drowsiness.
• Antibiotics (e.g. doxycycline 50–100 mg daily for 6 weeks,
azithromycin 500 mg once daily for 3 days) may be given to
reduce blepharitis-aggravated inflammation, usually in AKC.
• Immunosuppressive agents (e.g. steroids, ciclosporin,
tacrolimus, azathioprine) may be effective at relatively low
doses in AKC unresponsive to other measures. Short courses
of high-dose steroids may be necessary to achieve rapid
control in severe disease. Monoclonal antibodies against T
cells have shown some promise in refractory cases.
• Other treatments that may be effective in some patients
include aspirin in VKC (avoided in children and adolescents
due to Reye syndrome risk), allergen desensitization, and
plasmapheresis in patients with high serum IgE levels.
Surgery
• Superficial keratectomy may be required to remove plaques
or debride shield ulcers and allow epithelialization. Medical
treatment must be maintained until the cornea has
re-epithelialized in order to prevent recurrences. Excimer
laser phototherapeutic keratectomy is an alternative.
• Surface maintenance/restoration surgery such as
amniotic membrane overlay grafting or lamellar
keratoplasty, or eyelid procedures such as botulinum
toxin-induced ptosis or lateral tarsorrhaphy, may be
required for severe persistent epithelial defects or ulceration.
Gluing may be appropriate for focal (‘punched-out’) corneal
perforations.
Non-allergic eosinophilic conjunctivitis
Non-allergic eosinophilic conjunctivitis (NAEC) is a recently pro-
posed chronic non-atopic condition said to occur predominantly
in middle-aged women in whom dry eye is also commonly present;
it has been suggested that it is relatively common but under-
5
CHAPTER
Conjunctiva 151
diagnosed. It is thought to be of similar pathogenesis to non-
allergic eosinophilic rhinitis; conjunctival eosinophilia is present
without significant IgE levels in the serum or tear film. Symptoms
are similar to those of allergic conjunctivitis – itching, redness,
foreign body sensation and mild watery discharge. Treatment is
with a 1–2 week course of topical steroid for exacerbations fol-
lowed by maintenance with topical mast cell stabilizers, non-
steroidal anti-inflammatory agents or antihistamines.
Contact allergic blepharoconjunctivitis
Analogous to contact dermatitis, this refers to the acute or sub­
acute T-cell-mediated delayed hypersensitivity reaction seen most
commonly by ophthalmologists as a reaction to eye drop constitu-
ents and by optometrists as a reaction to contact lens solutions.
Mascara is a less common cause. There may be a conjunctival
reaction, but signs predominantly involve the eyelid skin: ery-
thema, thickening, induration and sometimes fissuring occur (Fig.
5.17). Treatment is by removal or discontinuation of the precipi-
tant, sometimes with a mild topical steroid ointment.
Giant (mechanically induced)  
papillary conjunctivitis
Pathogenesis
Mechanically induced papillary conjunctivitis, the severe form of
which is known as giant papillary conjunctivitis (GPC), can occur
secondary to a variety of mechanical stimuli of the tarsal conjunc-
tiva. It is most frequently encountered with contact lens (CL)
wear, when it is termed contact lens-associated papillary conjunc-
tivitis (CLPC). The risk is increased by the build-up of proteina-
ceous deposits and cellular debris on the contact lens surface.
Ocular prostheses (Fig. 5.18), exposed sutures and scleral buckles,
corneal surface irregularity and filtering blebs can all be responsi-
ble. A related phenomenon is the so-called ‘mucus fishing syn-
drome’, when, in a variety of underlying anterior segment
disorders, patients develop or exacerbate a chronic papillary
Fig. 5.17  Contact allergic blepharoconjunctivitis
152 Conjunctivitis in Blistering Mucocutaneous Disease
Fig. 5.18  Ocular prosthesis causing giant papillary
conjunctivitis
reaction due to repetitive manual removal of mucus. Giant papil-
lae can also be seen in other conditions such as VKC and AKC.
Diagnosis
• Symptoms consist of a foreign body sensation, redness,
itching, increased mucus production, blurring and loss of
CL tolerance. Symptoms may be worse after lens removal.
Patients should be questioned about CL cleaning and
maintenance.
• Signs
○ Variable mucous discharge.
○ Substantial CL protein deposits may be present.
○ Excessive CL mobility due to upper lid capture.
○ Superior tarsal hyperaemia and papillae; by definition,
‘giant’ papillae are >1.0 mm in diameter, but the clinical
syndrome of mechanically induced papillary
conjunctivitis commonly features only fine/medium
papillae, particularly in early or mild disease.
○ Focal apical ulceration and whitish scarring may develop
on larger papillae.
○ Keratopathy is rare because of the relatively subdued
secretion of inflammatory cytokines.
○ Ptosis may occur, mainly as a result of irritative spasm
and tissue laxity secondary to chronic inflammation.
Treatment
Other causes of conjunctival papillae should be excluded, as well
as CL intolerance due to other causes, such as a reaction to lens
cleaning solutions and dry eyes.
• Removal of the stimulus
○ CL wear should be discontinued for several weeks and
the current lenses replaced. For mild–moderate disease,
this may be adequate for resolution, sometimes in
conjunction with reduced wearing time. In severe CLPC
a longer interval without lens wear may be needed.
○ Removal of other underlying causes, such as exposed
sutures or a scleral buckle.
○ Assessment of the status and fit of an ocular prosthesis.
○ Filtering bleb: partial excision, revision with non-
penetrating drainage surgery or glaucoma drainage device
implantation.
• Ensure effective cleaning of CL or prosthesis
○ Changing the type of CL solution, particularly
discontinuation of preservative-containing preparations.
○ Switching to monthly then daily disposable CL if the
condition persists after renewing non-disposable lenses.
○ Rigid lenses carry a lesser risk of CLPC (5%), probably
because they are easier to clean effectively.
○ Cessation of contact lens wear, substituting spectacles or
refractive surgery, may be necessary for severe or
refractory disease.
○ Regular (at least weekly) use of contact lens protein
removal tablets.
○ Prosthesis: polishing, cleaning with detergent, coating.
• Topical
○ Mast cell stabilizers should be non-preserved in patients
wearing soft contact lenses, or can be instilled when the
lenses are not in the eye, with a delay of perhaps half an
hour after drop instillation prior to lens insertion. Most
can be continued long-term if necessary.
○ Antihistamines, non-steroidal anti-inflammatory agents
and combined antihistamines/mast cell stabilizers may
each be of benefit.
○ Topical steroids can be used for the acute phase of
resistant cases, particularly those where effective removal
of the stimulus is difficult, as in bleb-related disease.
CONJUNCTIVITIS IN BLISTERING
MUCOCUTANEOUS DISEASE
Mucous membrane pemphigoid
Introduction
Mucous membrane pemphigoid (MMP), also known as cicatricial
pemphigoid (CP), comprises a group of chronic autoimmune
mucocutaneous blistering diseases. An unknown trigger leads to
a Type II (cytotoxic) hypersensitivity response resulting in anti-
bodies binding at the basement membrane zone (BMZ), the acti-
vation of complement and the recruitment of inflammatory cells,
with localized separation of the epidermis from the dermis at the
BMZ and subsequent progression to scarring.
A wide range of epithelial tissues can be involved, including
the skin and various mucous membranes. Particular clinical
forms of MMP tend to involve specific target tissues: bullous pem-
phigoid (BP) shows a predilection for skin, and ocular mucous
membrane pemphigoid (OMMP, also known as ocular cicatricial
pemphigoid – OCP) involves the conjunctiva in the majority of
cases and causes progressive scarring (cicatrization). The disease
 5
CHAPTER
Conjunctiva 153

typically presents in old age and affects females more commonly
than males by a 2 : 1 ratio. Other causes of cicatrizing conjunctivitis
include Stevens–Johnson syndrome, trachoma, drug-induced,
trauma and severe or chronic conjunctivitis of many types. MMP
should not be confused with pemphigus, a distinct group of
disorders.
Ocular features
Diagnosis is principally clinical, but biopsy of involved mucous
membrane often shows supportive changes (linear antibody and
complement BMZ deposition). Progression has been divided into
stages, from stage I (chronic conjunctivitis) to stage IV (immobile
globe with a keratinized cornea).
• Symptoms. Insidious or relapsing–remitting non-specific
bilateral conjunctivitis; misdiagnosis (e.g. dry eye) is
common.
• Conjunctiva
○ Papillary conjunctivitis, diffuse hyperaemia, oedema and
subtle fibrosis (Fig. 5.19A).
○ Fine lines of subconjunctival fibrosis and shortening of
the inferior fornices; symblepharon (plural symblephara)
formation refers to adhesion between the bulbar and
palpebral conjunctiva (Fig. 5.19B).
○ Necrosis in severe cases.
○ Flattening of the plica and keratinization of the caruncle
(Fig. 5.19C).
○ Dry eye due to destruction of goblet cells and accessory
lacrimal glands, and occlusion of the main lacrimal
ductules.
○ Monitoring should include the measurement of forniceal
depth and noting the position of adhesions.
• Eyelids
○ Aberrant (trichiatic) lashes, chronic blepharitis and
keratinization of the lid margin.
○ Ankyloblepharon is an adhesion at the outer canthus
between the upper and lower lids (Fig. 5.19D).
• Cornea
○ Epithelial defects (Fig. 5.20A) associated with drying and
exposure.
○ Infiltration and peripheral vascularization (Fig. 5.20B).

A B

C D

Fig. 5.19  Conjunctivitis in ocular cicatricial pemphigoid. (A) Subtle disease with hyperaemia and early conjunctival fibrosis;
(B) moderate fibrosis with forniceal shortening and symblepharon formation; (C) flat plica and keratinized caruncle;
(D) ankyloblepharon
(Courtesy of S Tuft – fig. C)
154 Conjunctivitis in Blistering Mucocutaneous Disease

A B

C D

Fig. 5.20  Keratopathy in ocular cicatricial pemphigoid. (A) Epithelial defect; (B) peripheral vascularization and infiltration;
(C) keratinization with ankyloblepharon; (D) end-stage disease
(Courtesy of S Tuft – figs A–C)

○ Keratinization and conjunctivalization of the corneal • Antimetabolites (e.g. azathioprine, methotrexate,

surface (Fig. 5.20C) due to epithelial stem cell failure.
○ End-stage disease is characterized by total symblepharon
and corneal opacification (Fig. 5.20D).
Systemic features
• Mucosal involvement is very common and is characterized
by subepidermal blisters, most frequently oral (Fig. 5.21A).
Severe manifestations include oesophageal and laryngeal
strictures.
• Skin lesions are less common (25%) and present as tense
blisters and erosions of the head and neck, groin and
extremities (Fig. 5.21B).
Systemic treatment
Systemic treatment is the mainstay of management; any detectable
inflammatory activity should be suppressed.
• Dapsone (diaminodiphenylsulfone) is a useful first-line
treatment in patients with mild–moderate disease;
approximately 70% of patients respond. It is contraindicated
in glucose-6-phosphate dehydrogenase deficiency.
Sulfasalazine is sometimes better tolerated.
mycophenolate mofetil) are alternatives for mild–moderate
disease if dapsone is contraindicated, ineffective or poorly
tolerated, and are suitable for long-term therapy. Dapsone
can be used in conjunction if necessary. Cyclophosphamide
may be reserved for severe or refractory disease.
• Steroids (prednisolone 1–1.5 mg/kg) are effective for rapid
disease control, but adverse effects limit long-term use. IOP
should be monitored.
• Other measures include intravenous immunoglobulin
therapy and rituximab; remission has been reported with a
combination regimen.
Local treatment
• Topical
○ Artificial tears are an integral part of most regimens.
○ Topical steroids, ciclosporin or tacrolimus may be used
as an adjunct to systemic immunosuppressive treatment.
○ Retinoic acid may reduce keratinization.
○ Antibiotics when indicated.
○ Lid hygiene and low-dose oral tetracycline for
blepharitis.
 5
CHAPTER
Conjunctiva 155

A B

Fig. 5.21  Mucous membrane pemphigoid. (A) Oral blisters; (B) severe skin blistering
(Courtesy of S Tuft – fig. A)

• Subconjunctival mitomycin C and/or steroid injection may
be used as a temporizing aid or if systemic
immunosuppression is not possible.
• Contact lenses may be used with caution to protect the
cornea from aberrant lashes and from dehydration.
Reconstructive surgery
Reconstructive surgery, preferably under systemic steroid cover,
should be considered when active disease is controlled.
• Aberrant eyelashes (see Ch. 1).
• Punctal occlusion to aid tear retention.
• Lateral tarsorrhaphy or botulinum toxin-induced ptosis may
be used to promote healing of corneal epithelial defects.
• Entropion repair: conjunctival incision is avoided if
possible.
• Cataract surgery is commonly required.
• Mucous membrane autografting or amniotic membrane
transplantation for conjunctival resurfacing and forniceal
restoration.
• Limbal stem cell transfer may be attempted for corneal
re-epithelialization.
• Keratoplasty carries a high risk of failure; lamellar grafts may
be effective for perforation.
• Keratoprosthesis (Fig. 5.22) may be the only option in
end-stage disease.
However, it is now believed that erythema multiforme (without
the ‘major’) is a distinct disease, milder and recurrent, with some-
what dissimilar clinical features. Toxic epidermal necrolysis (TEN
– Lyell syndrome) is a severe variant of SJS. SJS/TEN patients tend
to be young adults, though other groups may be affected. The
condition involves a cell-mediated delayed hypersensitivity reac-
tion, usually related to drug exposure. A wide range of medica-
tions have been incriminated, including antibiotics (especially
sulfonamides and trimethoprim), analgesics including paraceta-
mol (acetaminophen), cold remedies and anticonvulsants. Infec-
tions due to microorganisms such as Mycoplasma pneumoniae and
herpes simplex virus, and some cancers have also been implicated.
Because symptoms often take weeks to develop, in many cases the
precipitant cannot be identified. Mortality overall is around 5% in
SJS (death is commonly due to infection), but is considerably
higher in TEN.

Stevens–Johnson syndrome/ 
toxic epidermal necrolysis  
(Lyell syndrome)
Introduction
The terms ‘Stevens–Johnson syndrome (SJS)’ and ‘erythema
multiforme major’ have historically been used synonymously. Fig. 5.22  Keratoprosthesis for severe conjunctival scarring
156 Conjunctivitis in Blistering Mucocutaneous Disease
Ocular features
In the acute stage there are often practical obstacles to standard
slit lamp examination; the patient may be bedridden and undergo-
ing barrier nursing; a portable slit lamp may be helpful.
• Symptoms. Acute ocular symptoms may include redness,
mild–severe grittiness, photophobia, watering and blurring.
• Acute signs
○ Haemorrhagic crusting of the lid margins (Fig. 5.23A) is
characteristic; skin lesions may be confluent and it is
often difficult for an examiner to open the eyes without
causing marked discomfort.
○ Papillary conjunctivitis, which can range from mild,
transient and self-limiting to severe (Fig. 5.23B).
○ Conjunctival membranes and pseudomembranes
(Fig. 5.23C), severe hyperaemia, haemorrhages, blisters
and patchy infarction.
○ Keratopathy: a spectrum of lesions from punctate
erosions to large epithelial defects, secondary bacterial
keratitis and occasionally perforation.
○ Iritis is not infrequent, and panophthalmitis has been
reported.
• Late signs
○ Conjunctival cicatrization (Fig. 5.23D) with forniceal
shortening and symblepharon formation.
○ Keratinization of the conjunctiva and lid margin
(Fig. 5.23E), sometimes with abrasive plaque formation.
○ Eyelid complications include cicatricial entropion and
ectropion, trichiasis, metaplastic lashes and
ankyloblepharon.
○ Keratopathy including scarring, vascularization and
keratinization (Fig. 5.23F) as a result of the primary
inflammation and/or infection, as well as cicatricial
entropion and aberrant lashes.
○ Watery eyes due to fibrosis of the lacrimal puncta. Dry
eyes may also occur as a result of fibrosis of lacrimal
gland ductules and conjunctival metaplasia with loss of
goblet cells.
Systemic features
Skin biopsy may help to establish the diagnosis but is rarely
necessary.
• Symptoms. Flu-like symptoms, which can be severe, may
last up to 14 days before the appearance of lesions. In many
cases the patient is very ill and hospitalization is required.
Symptoms of systemic mucosal involvement include nasal
pain and discharge, pain on micturition, diarrhoea, cough,
shortness of breath, and pain on eating and drinking.
• Signs
○ Mucosal involvement is characterized by blistering and
haemorrhagic crusting of the lips (Fig. 5.24A). The
blisters may also involve the tongue, oropharynx, nasal
mucosa and occasionally the genitalia.
○ Small purpuric, vesicular, haemorrhagic or necrotic
skin lesions involving the extremities, face and trunk
(Fig. 5.24B). These are usually transient but may be
widespread. Healing usually occurs within 1–4 weeks,
leaving a pigmented scar.
○ Widespread sloughing of the epidermis is uncommon.
○ ‘Target’ lesions showing the classic three zones are now
viewed as characteristic of erythema multiforme rather
than SJS/TEN.
Systemic treatment
• Removal of the precipitant if possible, such as
discontinuation of drugs and treatment of suspected
infection.
• General supportive measures such as maintenance of
adequate hydration, electrolyte balance and nutrition
(especially protein replacement) are critical. Management in
a specialist burns unit should reduce the chance of infection
when the extent of skin involvement is substantial.
• Systemic steroids remain controversial. There are reports of
increased mortality in older papers, but later research has
raised the possibility that early short-term high-dose
intravenous treatment may improve outcomes.
• Other immunosuppressants including ciclosporin,
azathioprine, cyclophosphamide and intravenous
immunoglobulin may be considered in selected cases, but
are controversial and controlled trials are lacking.
• Systemic antibiotics may be given as prophylaxis against
skin or other systemic infection, avoiding those known to be
at higher risk of precipitating SJS/TEN.
Ocular treatment
• Acute disease. Daily review is advisable initially in most
patients to check the corneas and exclude symblepharon
formation.
○ Topical lubricants are used as frequently as necessary, e.g.
hypromellose 0.3% preservative-free up to hourly,
high-viscosity ointment during sleep.
○ Prevention of corneal exposure, e.g. moisture chambers,
gel pads if mechanically ventilated.
○ Topical steroids may be used for iritis and for
conjunctival inflammation, though a benefit for the latter
has not been demonstrated conclusively.
○ Topical cycloplegia (e.g. atropine 1% once or twice daily)
may improve comfort.
○ Lysis of developing symblephara with a sterile glass rod
or damp cotton bud.
○ A scleral ring, consisting of a large haptic lens, may help
to prevent symblepharon formation (Fig. 5.25).
○ Pseudomembrane/membrane peeling can be considered,
although the benefit is unproven.
○ Treatment of acute corneal problems such as bacterial
keratitis; the use of prophylactic topical antibiotics is
common, but as there may be a propensity to adverse
drug reactions a decision should be made on a case basis.
○ Conjunctival swabs should be considered for prophylactic
culture.
 5
CHAPTER
Conjunctiva 157

A B

C D

E F

Fig. 5.23  Ocular features of Stevens–Johnson syndrome. (A) Haemorrhagic lid crusting; (B) severe acute conjunctivitis;
(C) pseudomembrane; (D) conjunctival scarring; (E) keratinization with severe lid margin involvement; (F) corneal
keratinization
(Courtesy of R Bates – fig. A; S Tuft – figs D, E and F)
158 Miscellaneous Conjunctivitides
A
B
Fig. 5.24  Systemic features in Stevens–Johnson syndrome.
(A) Haemorrhagic lip crusting; (B) extensive purpuric
lesions
(Courtesy of M Zatouroff, from Physical Signs in General Medicine,
Mosby–Wolfe 1996 – fig. B)
○ IOP monitoring may be prudent, using portable
tonometry if necessary.
• Chronic disease
○ Adequate lubrication, including punctal occlusion if
required.
○ Topical transretinoic acid 0.01% or 0.025% may reverse
keratinization.
○ Treatment of aberrant lashes (see Ch. 1).
○ Bandage contact lenses (typically gas permeable scleral
lenses) to maintain surface moisture, protect the cornea
from aberrant lashes and address irregular astigmatism.
○ Mucous membrane grafting (e.g. buccal mucosa
autograft) for forniceal reconstruction.
○ Corneal rehabilitation may involve superficial
keratectomy for keratinization, lamellar corneal grafting
for superficial scarring (preferred to penetrating
keratoplasty), amniotic membrane grafting, limbal stem
cell transplantation, and keratoprosthesis implantation in
end-stage disease.
MISCELLANEOUS CONJUNCTIVITIDES
Superior limbic keratoconjunctivitis
Introduction
Superior limbic keratoconjunctivitis (SLK) is a relatively uncom-
mon chronic disease of the superior limbus and the superior
bulbar and tarsal conjunctiva. It affects one or both eyes of middle-
aged women, approximately 50% of whom have abnormal thyroid
function (usually hyperthyroidism); approximately 3% of patients
with thyroid eye disease have SLK. The condition is probably
under-diagnosed because symptoms are typically more severe
than signs. The course can be prolonged over years although
remission eventually occurs spontaneously. There are similarities
to mechanically induced papillary conjunctivitis, and a compara-
ble clinical picture has been described with contact lens wear and
following upper lid surgery or trauma. The condition is believed
to be the result of blink-related trauma between the upper lid and
the superior bulbar conjunctiva, precipitated in many cases by tear
film insufficiency and an excess of lax conjunctival tissue. With
increased conjunctival movement there is mechanical damage to
the tarsal and bulbar conjunctival surfaces, the resultant inflam-
matory response leading to increasing conjunctival oedema and
redundancy, with the creation of a self-perpetuating cycle. It may
be analogous to conjunctivochalasis affecting the lower bulbar
conjunctiva (see Ch. 2).
Diagnosis
Enquiry should be made about contact lens wear, and previous
eyelid surgery or trauma.
• Symptoms include a foreign body sensation, burning, mild
photophobia, mucoid discharge and frequent blinking, and
are often intermittent.
Fig. 5.25  Scleral ring used to prevent symblepharon
formation in Stevens–Johnson syndrome
(Courtesy of S Tuft)
 5
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Conjunctiva 159

• Conjunctiva
○ Papillary hypertrophy of the superior tarsal plate, often
having a diffuse velvety appearance (Fig. 5.26A).
○ Hyperaemia of a radial band of the superior bulbar
conjunctiva (Fig. 5.26B) that stains with rose Bengal and
may be best seen macroscopically.
○ Limbal papillary hypertrophy (also Fig. 5.26B); limbal
palisades may be lost superiorly.
○ Light downward pressure on the upper lid results in a
fold of redundant conjunctiva crossing the upper limbus
(Fig. 5.26C).
○ Petechial haemorrhages may be present.
○ Keratinization can be demonstrated on biopsy or
impression cytology.
• Cornea
○ Superior punctate corneal epithelial erosions are common
and are often separated from the limbus by a zone of
normal epithelium.
○ Superior filamentary keratitis (Fig. 5.26D) develops in
about one-third of cases.
○ Mild superior pannus resembling arcus senilis may be
seen in long-standing disease.
○ Keratoconjunctivitis sicca is present in only about 50%.
• Investigation
○ Thyroid function testing should be performed if the
patient is not known to have thyroid disease.
○ Biopsy or impression cytology may reveal keratinization
of the superior bulbar conjunctiva.
Treatment
• Topical
○ Lubricants (preservative-free may be preferred) to reduce
friction between the tarsal and bulbar conjunctiva should
be used regularly and frequently.
○ Acetylcysteine 5% or 10% four times daily to break down
filaments and provide lubrication.
○ Mast cell stabilizers and steroids to address any
inflammatory component; steroids may be best used in
short intensive courses with rapid tapering, and should
be reserved for severe cases.
○ Promising results have been reported with topical
rebamipide.
○ Ciclosporin 0.05% twice daily as primary or adjunctive
therapy, particularly in the presence of coexisting
keratoconjunctivitis sicca.

A B

C D

Fig. 5.26  Superior limbic keratoconjunctivitis. (A) Diffuse velvety papillary hypertrophy; (B) hyperaemic band of superior bulbar
conjunctiva with limbal papillae, stained with rose Bengal; (C) fold of redundant conjunctiva; (D) superior corneal filaments
(Courtesy of S Tuft – fig. C)
160 Miscellaneous Conjunctivitides
○ Retinoic acid to retard keratinization.
○ Autologous serum 20% drops can be beneficial but may
require instillation up to 10 times a day.
• Soft contact lenses, which intervene between the lid
and the superior conjunctiva, are effective in some cases.
Interestingly, a unilateral lens may provide bilateral
relief.
• Supratarsal steroid injection. 0.1 ml of triamcinolone
40 mg/ml may break the inflammatory cycle.
• Temporary superior and/or inferior punctal
occlusion.
• Resection of the superior limbal conjunctiva, either in a
zone extending 2 mm from the superior limbus or of the
area staining with rose Bengal, is often effective in resistant
disease. Lax conjunctiva is removed, with regrowth tending
to be firmly anchored. There is no consensus as to whether
underlying Tenon capsule should be excised.
• Conjunctival ablation by applying silver nitrate 0.5% (not
cautery sticks) or thermocautery to the affected area.
• Treatment of associated thyroid dysfunction may improve
SLK.
Ligneous conjunctivitis
Introduction
Ligneous conjunctivitis is a very rare potentially sight- and even
life-threatening disorder characterized by recurrent, often bilateral
fibrin-rich pseudomembranous lesions of wood-like consistency
that develop mainly on the tarsal conjunctiva. It is generally a
systemic condition and may involve the periodontal tissue, the
upper and lower respiratory tract, kidneys, middle ear and female
genitalia; death can occasionally occur from pulmonary involve-
ment. It is thought that in susceptible patients patterns of damage
repair are abnormal, notably a failure of normal clearance of prod-
ucts of the acute stages of the healing process. This is manifested
predominantly in mucosal tissue. A deficiency in plasmin-mediated
fibrinolysis may be a key common factor in many patients.
Episodes may be triggered by relatively minor trauma, or by sys-
temic events such as fever and antifibrinolytic therapy.
Diagnosis
• Presentation is with nonspecific conjunctivitis, usually in
childhood (median age 5 years), although onset may be at
any age. A conjunctival lesion is commonly noted by
parents.
• Signs
○ Gradually enlarging red–white lobular conjunctival
masses (Fig. 5.27A and B); may be covered by a thick
yellow–white mucoid discharge.
○ Corneal scarring, vascularization, infection or
melting.
• Histopathology shows amorphous subepithelial deposits of
eosinophilic material consisting predominantly of fibrin
(Fig. 5.27C).
Treatment
Treatment tends to be unsatisfactory and spontaneous resolution
is rare. It is important to discontinue any antifibrinolytic drugs.
• Surgical removal (Fig. 5.27D) with meticulous diathermy of
the base of the lesion. Preoperative topical plasminogen may
soften pseudomembranes and facilitate removal.
• Topical
○ Following membrane removal, hourly heparin and
steroids are commenced immediately and continued until
the wound has re-epithelialized, with subsequent tapering
over several weeks until all signs of inflammation have
disappeared.
○ Recurrence may be retarded by long-term ciclosporin and
steroid instillation.
• Other modalities
○ Intravenous or topical plasminogen.
○ Amniotic membrane transplantation to the conjunctiva
following lesion removal.
○ Prophylactic heparin treatment may be of benefit prior to
ocular surgery in at-risk patients.
Parinaud oculoglandular syndrome
Parinaud oculoglandular syndrome is a rare condition consisting
of chronic low-grade fever, unilateral granulomatous conjunctivi-
tis (Fig. 5.28) with surrounding follicles, and ipsilateral regional
(preauricular) lymphadenopathy. It is virtually synonymous with
cat scratch disease (caused by Bartonella henselae – see Ch. 11),
although several other causes have been implicated, including
tularaemia, insect hairs (ophthalmia nodosum), Treponema pal-
lidum, sporotrichosis, tuberculosis, and acute C. trachomatis
infection.
Factitious conjunctivitis
Introduction
Self-injury (factitious keratoconjunctivitis) is most often inten-
tional, but can also occur inadvertently, as in mucus fishing syn-
drome and removal of contact lenses. Damage may be the result
of either mechanical trauma or of the instillation of irritant but
readily accessible household substances, such as soap.
Occasionally over-instillation of prescribed ocular medication is
responsible.
Diagnosis
• Symptoms. Reported symptoms may seem disproportionate
to signs; the patient may have sought multiple medical
opinions over an extended period, often from a range of
specialists for different complaints.
• Signs
○ Inferior conjunctival injection and staining with rose
Bengal (Fig. 5.29), with quiet superior bulbar conjunctiva.
○ Linear corneal abrasions, persistent epithelial defects and
occasionally focal corneal perforation.
 5
CHAPTER
Conjunctiva 161

A B

C D

Fig. 5.27  Ligneous conjunctivitis. (A) and (B) Multiple ligneous lesions; (C) histology shows eosinophilic fibrinous coagulum on
the conjunctival surface; (D) lesion removal
(Courtesy of JH Krachmer, MJ Mannis and EJ Holland, from Cornea, Mosby 2005 – fig. B; J Harry and G Misson, from Clinical Ophthalmic Pathology, Butterworth-
Heinemann 2001 – fig. C; J Dart – fig. D)

Fig. 5.28  Granulomatous conjunctivitis in Parinaud syndrome Fig. 5.29  Inferior conjunctival injection and staining with rose
Bengal in factitious conjunctivitis
(Courtesy of S Tuft)
162 Degenerations

○ Secondary infection with Candida spp.

○ Sterile ring infiltrate and hypopyon.
○ Corneal scarring.

Management
• Exclude other diagnoses.
• Close observation may be required.
• Confrontation often leads to failure to return for review.
• A psychiatric opinion may be appropriate.

DEGENERATIONS A

Pinguecula
Introduction
A pinguecula (plural pingueculae) is an innocuous but extremely
common asymptomatic elastotic degeneration of the conjunctival
stroma. A yellow–white mound or aggregation of smaller mounds
is seen on the bulbar conjunctiva adjacent to the limbus (Fig.
5.30A). It is more frequently located at the nasal than the temporal
limbus, but is frequently present at both. Calcification (Fig. 5.30B)
is occasionally present. The cause is believed to be actinic damage,
similar to the aetiology of pterygium (see below), which pinguec-
ula resembles histologically; the distinction is that the limbal
barrier to extension has remained intact with a pinguecula, though
transformation can occur. Occasionally a pingueculum may B
become acutely inflamed (pingueculitis – Fig. 5.30C), often if the
lesion is prominent or overlying calcification leads to epithelial
breakdown.

Treatment
Treatment is usually unnecessary because growth is absent or very
slow.
• Irritation may be treated with topical lubrication.
• Pingueculitis can be treated with lubrication if mild or with
a short course of topical steroid.
• Excision may be indicated for cosmetic reasons or for
significant irritation; in contrast to pterygium (see next), the
recurrence rate is very low and simple excision is usually
adequate.
• Thermal laser ablation can be effective; gentian violet
marking may be necessary to ensure adequate absorption in C
lighter-skinned individuals.
Fig. 5.30  (A) Pinguecula; (B) developing calcification;
Pterygium (C) pingueculitis

such as chronic surface dryness. A pterygium is histologically

Introduction
A pterygium (plural pterygia) is a triangular fibrovascular subepi-
thelial ingrowth of degenerative bulbar conjunctival tissue over
the limbus onto the cornea. It typically develops in patients who
have been living in hot climates and, as with pinguecula, may
represent a response to ultraviolet exposure and to other factors
similar to a pinguecula and shows elastotic degenerative changes
in vascularized subepithelial stromal collagen (Fig. 5.31A). In con-
trast to pingueculae, pterygia encroach onto the cornea, invading
the Bowman layer. Pseudopterygium appears similar clinically but
is caused by a band of conjunctiva adhering to an area of compro-
mised cornea at its apex. It forms as a response to an acute
 5
CHAPTER
Conjunctiva 163

A B

C D

Fig. 5.31  Pterygium. (A) Histology shows collagenous

degenerative changes in vascularized subepithelial stroma;
(B) pterygium showing cap, head and body; (C) Stocker line;
(D) high magnification of Fig. 5.31C showing Fuchs islets;
E (E) pseudopterygium secondary to a chemical burn
(Courtesy of J Harry – fig. A)
164 Degenerations

inflammatory episode such as a chemical burn, corneal ulcer

(especially if marginal), trauma and cicatrizing conjunctivitis.

Clinical features
• Symptoms. Patients who present with a history of recent
enlargement are more likely to require early excision for
subsequent aggressive growth. Aggressive growth or an
atypical appearance should prompt excision biopsy.
○ Most small lesions are asymptomatic.
○ Irritation and grittiness are caused by a dellen – localized
drying – effect at the advancing edge due to interference
with the precorneal tear film (more likely if the head of
the pterygium is especially elevated).
○ Patients who wear contact lenses may develop symptoms A
of irritation at an earlier stage due to edge lift.
○ Lesions may interfere with vision by obscuring the visual
axis or inducing astigmatism.
○ There may be intermittent inflammation similar to
pingueculitis.
○ Cosmesis may be a significant problem.
○ Extensive lesions, particularly if recurrent, may be
associated with subconjunctival fibrosis extending to the
fornices that may cause restricted ocular excursion.
○ If pseudopterygium is suspected, there may be a history
of a causative episode.
• Signs
○ A pterygium is made up of three parts: a ‘cap’ (an
avascular halo-like zone at the advancing edge), a head
and a body (Fig. 5.31B).
○ Linear epithelial iron deposition (Stocker line) may be B
seen in the corneal epithelium anterior to the head of the
pterygium (Fig. 5.31C). Fig. 5.32  Surgical treatment of pterygium. (A) Excision site
○ Fuchs islets (Fig. 5.31D) are small discrete whitish flecks
one week postoperatively showing sutured conjunctival
autograft; (B) autograft donor site at superior limbus
consisting of clusters of pterygial epithelial cells often
present at the advancing edge.
○ A pseudopterygium (Fig. 5.31E) is classically distinguished conjunctival grafts and amniotic membranes can be
by both location away from the horizontal (though this secured with tissue glue rather than sutured, shortening
may also be seen with true pterygia) and firm attachment operating time and reducing postoperative irritation.
to the cornea only at its apex (head). ○ Adjunctive treatment with mitomycin C or beta-
irradiation are sometimes used in place of patching
Treatment techniques.
○ Peripheral lamellar keratoplasty may be required for deep
• Medical treatment of symptomatic patients is as for
lesions.
pinguecula. The patient may be advised to wear sunglasses
to reduce ultraviolet exposure in order to decrease the
growth stimulus.
Concretions
• Surgery. Simple excision (‘bare sclera’ technique) is Concretions are extremely common and are usually associated
associated with a high rate of recurrence (around 80%), with ageing, although they can also form in patients with chronic
often with more aggressive behaviour than the original conjunctival inflammation such as trachoma. They appear as
lesion. multiple tiny cysts containing yellowish–white deposits of epithe-
○ Simple conjunctival flap. lial debris including keratin, commonly located subepithelially in
○ Conjunctival autografting (Fig. 5.32A). The donor the inferior tarsal and forniceal conjunctiva (Fig. 5.33A). They can
conjunctival patch is usually harvested from the superior become calcified and, particularly if large, may erode the overlying
or superotemporal paralimbal region (Fig. 5.32B) the site epithelium (Fig. 5.33B) and cause marked irritation. Treatment if
generally heals rapidly, even without suturing. Amniotic symptomatic involves removal at the slit lamp with a needle under
membrane patch grafting is an alternative. Both topical anaesthesia.

B inclusion) cyst
Fig. 5.33  (A) Multiple small concretions; (B) large concretion
eroding through the conjunctival surface
Conjunctivochalasis
Conjunctivochalasis usually appears as a fold of redundant con-
junctiva interposed between the globe and lower eyelid, protrud-
ing over the lid margin (Fig. 5.34). It is probably a normal ageing
change that may be exacerbated by inflammation and mechanical
stress related to dry eye and lid margin disease. Symptoms include
watering of the eye due to obstruction of the inferior punctum and
interference with the marginal tear meniscus. Treatment consists
of topical lubricants and treatment of any blepharitis. A short
Fig. 5.34  Conjunctivochalasis
5
CHAPTER
Conjunctiva 165
Fig. 5.35  Conjunctival cyst
course of topical steroids or other anti-inflammatory agent may
be helpful. Conjunctival resection can be performed in severe
cases (see also Ch. 2).
Retention (primary epithelial  
Conjunctival retention cysts are thin-walled lesions on the bulbar
conjunctiva containing clear (Fig. 5.35) or occasionally turbid
fluid. They do not usually cause discomfort but may be a mild
cosmetic blemish. Histology shows a fluid-filled internal cavity
lined by a double epithelial layer. Treatment, if required, is initially
by simple puncture with a needle under topical anaesthesia, but
recurrence is common. Bleeding should be encouraged within the
ruptured cyst as it may promote adhesion of the walls and reduce
the chance of recurrence. Cyst wall excision under topical anaes-
thesia can be carried out for recurrences. The differential diagnosis
includes secondary inclusion cysts following conjunctival surgery,
and lymphangiectasia. The latter is characterized by strings of
cystic or sausage-shaped clear-walled channels, which may become
filled with blood (haemorrhagic lymphangiectasia – Fig. 5.36).
Fig. 5.36  Haemorrhagic lymphangiectasia
166 Subconjunctival Haemorrhage
Fig. 5.37  Subconjunctival haemorrhage
SUBCONJUNCTIVAL HAEMORRHAGE
Subconjunctival haemorrhage (Fig. 5.37) is a very common phe-
nomenon that may result from surgery, conjunctivitis and trauma
(from minor unnoticed to severe skull base), but is often idio-
pathic and apparently spontaneous, particularly in older patients.
The bleed is usually asymptomatic until noticed by the patient or
others; a momentary sharp pain or a snapping or popping sensa-
tion is sometimes felt. Coughing, sneezing and vomiting are
common precipitants. In younger people contact lens wear is a
common association, and in older individuals systemic vascular
disease is prevalent, especially hypertension, and blood pressure
should be checked. A local ocular cause should be ruled out by slit
lamp examination. Bleeding diatheses are a very rare association,
but vitamin C deficiency and abusive trauma should always be
considered in infants. The vision is usually unaffected unless a
substantially elevated haemorrhage leads to a large localized
corneal wetting deficit (dellen), which is often uncomfortable. A
large bleed can track into the eyelids. Spontaneous resolution over
a week or two is typical, but two or three narrowly spaced episodes
are not uncommon.
WHO GUIDELINES FOR THE

Treatment of
Neisseria gonorrhoeae
 RECOMMENDATIONS FOR TREATMENT OF GONOCOCCAL INFECTIONS
04
RECOMMENDATIONS
FOR TREATMENT
OF GONOCOCCAL
INFECTIONS
The following six recommendations apply
to adults, adolescents (10–19 years of age),
people living with HIV, and key populations,
including sex workers, men who have sex
with men (MSM) and transgender persons.
Specific recommendations have also been
developed for ophthalmia neonatorum
caused by N. gonorrhoeae.
4.1 GENITAL AND ANORECTAL
GONOCOCCAL INFECTIONS
RECOMMENDATION 1
The WHO STI guideline recommends that local
resistance data should determine the choice of
therapy (both for dual therapy and single therapy).
Good practice statement
In settings where local resistance data are not available,
the WHO STI guideline suggests dual therapy over single
therapy for people with genital or anorectal gonorrhoea.
Conditional recommendation, low quality evidence
The WHO STI guideline suggests the following options:
Dual therapy (one of the following)
17
• c eftriaxone 250 mg intramuscular (IM) as a single
dose PLUS azithromycin 1 g orally as a single dose
• c efixime 400 mg orally as a single dose PLUS
azithromycin 1 g orally as a single dose
Single therapy (one of the following, based on recent
local resistance data confirming susceptibility to
the antimicrobial)
• ceftriaxone 250 mg IM as a single dose
• cefixime 400 mg orally as a single dose
• spectinomycin 2 g IM as a single dose.
Remarks: Because of the emerging resistance data
for gonococcal infections and reduced effectiveness
of some medicines, good practice dictates that the
choice of treatment depends on reliable local data on
antimicrobial susceptibility. Alternative single-medicine
therapies, such as gentamicin or kanamycin, have
not been suggested due to lack of surveillance data.
Guidance for surveillance of antimicrobial resistance
(AMR) in N. gonorrhoeae is available from WHO (16).
This recommendation applies to pregnant women,
who should be closely monitored.
SUMMARY OF THE EVIDENCE
The quality of the evidence for the effects of treatments
for gonococcal infections is low. Evidence is available
from 108 studies, including 14 randomized and 94
non-randomized studies, which were conducted in
a broad range of high-, middle- and low-income
countries. Although high cure rates were shown
(> 95%), the evidence is outdated and regionally
specific, and therefore is considered to be indirect due
to emerging resistance data. Available data on AMR
in N. gonorrhoeae revealed high rates of resistance to
quinolones, emerging azithromycin resistance and
decreased susceptibility to ceftriaxone and cefixime.
Low quality evidence suggests similar cure rates with
azithromycin using single doses of 1 g or 2 g, but there
are data on emerging resistance for azithromycin
from many countries. Cure rates for kanamycin and
gentamycin vary and are based on older studies.
Currently, there is little surveillance data for these two
medicines. There are similar cure rates with cefixime
using single doses of 400 mg or 800 mg. The evidence
for dual versus single therapy is low quality, as there
are few studies evaluating different combinations
with azithromycin. Side-effects of the medicines were
often not measured, but when measured were trivial.
In particular, the evidence for differences in side-effects
between 1 g or 2 g single doses of azithromycin is
uncertain, but the Guideline Development Group (GDG)
agreed that side-effects, such as nausea, could be
greater with higher doses.
18 WHO GUIDELINES FOR THE TREATMENT OF NEISSERIA GONORRHOEAE
Overall, the GDG therefore agreed that the success
of the available treatments is based on in vitro
susceptibility of gonococcal infections, and should
therefore be based on recent local surveillance data.
Due to global resistance patterns, quinolones are no
longer an option for treatment of gonococcal infections.
The GDG agreed that dual therapy should be suggested
due to the emergence of resistance and the paucity of
surveillance data in most settings to guide decisions
about susceptibility to single therapy. Additional studies
comparing different combinations of dual therapy (such
as gentamicin, ceftriaxone, cefixime or gemifloxacin plus
azithromycin) will inform recommendations in future.
No studies were found that assessed patient values
and preferences, acceptability, equity or feasibility
specific to gonococcal infections. There is some
evidence from the literature about acceptability of
injections versus oral medications in people with
syphilis. Approximately 10–20% of people refused
injections. The GDG also noted that some health-care
providers are, in practice, averse to providing injections,
and that additional labour time and costs are associated
with IM administration. The GDG agreed that there is
probably no variability in the values people place on
the outcomes. However, IM injection may be less
desirable among patients than oral administration,
and dual therapy is acceptable to patients based on
current use. Although azithromycin is perceived by
some GDG members to require greater resources,
the costs of the suggested treatments were similar.
Since azithromycin is currently recommended for
treatment of other STIs (e.g. chlamydia), it may provide
additional benefit by treating possible co-infections.
For pregnant women: The quality of evidence for
the effects of treatments for genital and anorectal
gonococcal infections in pregnant women is low.
Evidence was reviewed from three studies, including
two randomized studies and one non-randomized
study. When data for pregnant women were not
available, evidence in non-pregnant adults was used
to inform the recommendations.
In summary, there is low quality evidence for benefits
and harms of dual therapy compared to single therapy,
but due to emerging resistance to single therapies
and lack of local surveillance data in most regions,
dual therapy is favoured over single therapy.
Dual therapy is currently being used in some settings
and it appears to be acceptable, and the costs compared
to effectiveness are not greater than single therapy.
See Annex C for list of references of reviewed evidence,
and Web annex D for details of the evidence reviewed,
including evidence profiles and evidence-to-decision
frameworks (pp. 1-24).
4.2 OROPHARYNGEAL
GONOCOCCAL INFECTIONS
RECOMMENDATION 2
In adults and adolescents with gonococcal
oropharyngeal infections, the WHO STI guideline
suggests dual therapy over single therapy.
Conditional recommendation, very low quality evidence
The WHO STI guideline suggests the following options:
Dual therapy (one of the following)
• c eftriaxone 250 mg IM as a single dose PLUS
azithromycin 1 g orally as a single dose
• c efixime 400 mg orally as a single dose PLUS
azithromycin 1 g orally as a single dose
 ingle therapy (based on recent local resistance data
S
confirming susceptibility to the antimicrobial)
• ceftriaxone 250 mg IM as single dose.
Remarks: Treatment failures have been observed
after single therapy for gonococcal oropharyngeal
infections and therefore dual therapy is suggested
over single therapy. This recommendation applies to
pregnant women, who should be closely monitored
for complications.
SUMMARY OF THE EVIDENCE
The quality of the evidence for the effects of different
treatments for oropharyngeal gonococcal infections is
low and very low, and therefore, overall, the evidence
for this recommendation is very low. Evidence from 28
studies was identified: eight randomized and 20 non-
randomized studies (including two non-randomized
studies with two or more groups, and 18 non-
randomized studies with one group). These studies
were conducted in a broad range of high-, middle- and
low-income countries. This evidence is outdated and
regionally specific, and therefore is considered to be
indirect due to emerging resistance data. The GDG
agreed that the success of the available treatments is
based on in vitro susceptibility of gonococcal infections,
and should therefore be based on recent local
surveillance data. Similar treatments were provided to
people with oropharyngeal infections and anorectal
infections (typically people had co-infection at other
sites). The data showed a higher risk of treatment failure
with oropharyngeal infections, and the GDG agreed
that the consequences of treatment failure are severe.
Based on these considerations, the GDG agreed that
treatment should be as aggressive for oropharyngeal
infections as for anorectal infections. Low quality
evidence showed that spectinomycin may result in l
ower cure rates (75%, ranging from 49% to 100%).
Data for the effects of gentamycin or kanamycin
are not available.
 RECOMMENDATIONS FOR TREATMENT OF GONOCOCCAL INFECTIONS
No studies were found to assess patient values
and preferences, acceptability, equity or feasibility.
The GDG agreed that there is probably no variability
in values. However, IM injection may be less desirable
than oral administration, and dual therapy is acceptable.
Although azithromycin may be perceived by health-care
providers, programme managers, policy-makers
and funders to require greater resources, in fact
the costs were similar across different treatments.
In summary, there is very low quality evidence for
benefits and harms of dual therapy compared to
single therapy, but due to emerging resistance to
single therapies and lack of local surveillance data in
most regions, dual therapy is favoured over single
therapy. Dual therapy is currently being used in some
settings and it appears to be acceptable, and the costs
compared to effectiveness are not greater than single
therapy. The recommendations for genital, anorectal
and oropharyngeal infections are similar; however,
single therapy with spectinomycin was less effective
in oropharyngeal infections.
See Annex C for list of references of reviewed evidence,
and Web annex D for details of the evidence reviewed,
including evidence profiles and evidence-to-decision
frameworks (pp. 25-38). 
19
4.3 RETREATMENT OF GONOCOCCAL
INFECTIONS AFTER TREATMENT FAILURE
RECOMMENDATION 3
In people with gonococcal infections who have failed
treatment, the WHO STI guideline suggests the
following options.
• I f reinfection is suspected, re-treat with a WHO-
recommended regimen, reinforce sexual abstinence
or condom use, and provide partner treatment.
• I f treatment failure occurred after treatment with a
regimen not recommended by WHO, re-treat with a
WHO-recommended regimen.
• I f treatment failure occurred and resistance data are
available, re-treat according to susceptibility.
• I f treatment failure occurred after treatment with a
WHO-recommended single therapy, re-treat with
WHO-recommended dual therapy.
• I f treatment failure occurred after a WHO-
recommended dual therapy, re-treat with one
of the following dual therapies:
−− ceftriaxone 500 mg IM as a single dose
PLUS azithromycin 2 g orally as a single dose
−− c efixime 800 mg orally as a single dose
PLUS azithromycin 2 g orally as a single dose
−− g
 entamicin 240 mg IM as a single dose
PLUS azithromycin 2 g orally as a single dose
−− s pectinomycin 2 g IM as a single dose (if not an
oropharyngeal infection) PLUS azithromycin
2 g orally as a single dose.
Conditional recommendation, very low quality evidence
Remarks: Before retreatment, reinfection should
be distinguished from treatment failure, resistance
data should be obtained when possible, and the
WHO-recommended regimens should be used.
20 WHO GUIDELINES FOR THE TREATMENT OF NEISSERIA GONORRHOEAE
SUMMARY OF THE EVIDENCE
The quality of the evidence is very low. The evidence
is from 34 randomized and non-randomized studies
that evaluated a treatment or many treatments and
then reported on retreatment of individual cases of
treatment failure. No studies specifically recruited
people who had treatment failure. Most studies
reported on cases of treatment failure or reinfection
(a distinction was often not made). These studies
also reported the medicine used for initial treatment,
the medicine used for retreatment, and sometimes
reported whether or not the case was cured.
Cure rates for different medicines were not
consistent across the studies.
In summary, there is very low quality evidence for
the effects of specific medicines for people who fail
treatment. Therefore, the recommendation was based
on first determining whether or not the initial treatment
was according to a WHO-recommended regimen;
if it was not, then retreatment is suggested according
to a WHO-recommended regimen; but if the initial
treatment was according to a WHO-recommended
regimen, then the suggestion for retreatment is for
increasing dosages.
See Annex C for list of references of reviewed evidence,
and Web annex D for details of the evidence reviewed,
including evidence profiles and evidence-to-decision
frameworks (pp. 39-63).
4.4 OPHTHALMIA NEONATORUM
RECOMMENDATION 4
In neonates with gonococcal conjunctivitis, the
WHO STI guideline suggests one of the following
treatment options:
• c eftriaxone 50 mg/kg (maximum 150 mg) IM as
a single dose
• k anamycin 25 mg /kg (maximum 75 mg) IM as a
single dose
• s pectinomycin 25 mg/kg (maximum 75 mg) IM
as a single dose.
Conditional recommendation, very low quality evidence
Remarks: Due to the large net benefit of treatment,
good practice dictates that neonates should be treated
for gonococcal conjunctivitis. The choice of treatment
may depend on the cost and quality of the medicine in
different settings and on equity considerations.
Side-effects should be monitored in neonates.
SUMMARY OF THE EVIDENCE
The evidence is from two randomized and 13
non-randomized studies. There was very low quality
evidence for cure rates, which were typically 100% for
all treatments, with the exception of penicillin (81–84%).
The quality of evidence was very low for adverse effects
across treatments, generally indicating little to
no difference among treatments. No evidence is
available for patient values and preferences.
The costs for treatments were relatively low and
similar, and most treatments are currently being used.
See Annex C for list of references of reviewed evidence,
and Web annex D for details of the evidence reviewed,
including evidence profiles and evidence-to-decision
frameworks (pp. 64-75).
RECOMMENDATION 5
For all neonates, the WHO STI guideline recommends
topical ocular prophylaxis for the prevention of
gonococcal and chlamydial ophthalmia neonatorum.
Strong recommendation, low quality evidence
 RECOMMENDATIONS FOR TREATMENT OF GONOCOCCAL INFECTIONS 21

RECOMMENDATION 6 Few data are available for the incidence of non-

infectious conjunctivitis after prophylaxis or no
For ocular prophylaxis, the WHO STI guideline suggests
prophylaxis. Low quality evidence shows a slight
one of the following options for topical application to
reduction or little difference and indicates that
both eyes immediately after birth:
between 4 and 50 per 1000 infants have non-infectious
• tetracycline hydrochloride 1% eye ointment conjunctivitis after application of different prophylactic
• erythromycin 0.5% eye ointment medications. There is little evidence for patient values
and preferences, but the GDG agreed that there would
• povidone iodine 2.5% solution (water-based)
likely be little difference in the high value placed on
• silver nitrate 1% solution avoiding long-term consequences of both gonococcal
• chloramphenicol 1% eye ointment. and chlamydial conjunctivitis. The GDG also agreed
that there would be little effect on acceptability,
Conditional recommendation, low quality evidence
equity and feasibility, as prophylaxis is currently used
Remarks: Recommendations 5 and 6 apply to the in many countries. The GDG reported that alcohol-
prevention of both chlamydial and gonococcal based povidone iodine has erroneously been used as
ophthalmia neonatorum. Cost and local resistance prophylaxis resulting in serious harm to babies.
to erythromycin, tetracycline and chloramphenicol Silver nitrate is the most expensive prophylaxis option.
in gonococcal infection may determine the choice of
In summary, there are large benefits for prophylaxis to
medication. Caution should be taken to avoid touching
prevent ophthalmia neonatorum, and these benefits
eye tissue when applying the topical treatment and
outweigh the risk of non-infectious conjunctivitis due
to provide a water-based solution of povidone iodine.
to prophylaxis with any of the topical medications.
Alcohol-based povidone iodine solution must not
Some topical medications may provide greater
be applied. The topical application should be
protection (tetracycline hydrochloride, erythromycin
administered immediately after birth.
or povidone iodine), but all are feasible to provide.
SUMMARY OF THE EVIDENCE See Annex C for list of references of reviewed evidence,
and Web annex D for details of the evidence reviewed,
Overall, the quality of the evidence is low to very low
including evidence profiles and evidence-to-decision
from 16 studies: 15 randomized studies and one non-
frameworks (pp. 76-93).
randomized study with two comparison groups.
There are few data for the effects of chloramphenicol.
Large benefits were reported for prophylaxis compared
with no prophylaxis, in particular in babies born to
women with known infection (approximately 70%
reduction in conjunctivitis with prophylaxis using
different medications). The benefits of treatment with
different medications are similar; however, the low to
very low quality evidence indicates that the benefits of
tetracycline hydrochloride, erythromycin or povidone
iodine may be slightly greater than for silver nitrate.
Pedoman Nasional Penanganan
INFEKSI MENULAR SEKSUAL
2015

Kementerian Kesehatan Republik Indonesia

Tahun 2015
 DIAGNOSIS DAN
PENGOBATAN INFEKSI
MENULAR SEKSUAL
Diagnosis pasien IMS dapat ditegakkan berdasarkan pendekatan sindrom bagi sarana
pelayanan kesehatan yang tidak memiliki fasilitas laboratorium, atau secara etiologis
berdasarkan hasil pemeriksaan laboratorium sederhana.

DIAGNOSIS IMS MENGGUNAKAN BAGAN ALUR

Dalam penggunaan bagan alur, dapat dilihat 3 macam kotak yang berbeda, masing-
masing mempunyai tujuan:

Kotak segi empat dengan sudut tumpul:

merupakan kotak masalah yang memberikan KOTAK MASALAH
keterangan tentang keluhan dan gejala, dan
merupakan awal dari setiap bagan alur.

Kotak segi enam: merupakan kotak keputusan

KOTAK KEPUTUSAN
yang selalu mempunyai dua alur keluar yang
mengarah ke kotak tindakan. Kedua alur itu adalah
alur “ya” dan alur “tidak”.

Kotak segi empat dengan sudut tajam: merupakan

KOTAK TINDAKAN
kotak tindakan. Kotak ini menunjukkan
penatalaksanaan yang harus dilakukan.

Selanjutnya akan dibahas tentang penatalaksanaan delapan sindrom klinis IMS yang sering
dijumpai.

Pedoman Nasional Penanganan Infeksi Menular Seksual 2015 | 21

 7. KONJUNGTIVITIS NEONATORUM

Konjungtivitis pada neonatus (oftalmia neonatorum) dapat berakhir dengan kebutaan bila
disebabkan oleh N. gonorrhoeae. Infeksi menular seksual patogen terpenting yang
menyebabkan oftalmia neonatorum adalah N. gonorrhoeae dan C. trachomatis. Di negara-
negara berkembang, penyebab konjungtivitis neonatorum ini adalah N. gonorrhoeae
diperkirakan berjumlah 20- 75 % dan C.trachomatis 15 - 35 %. Penyebab lainnya adalah
Staphyllococcus aureus, Streptococcus pneumoniae, Haemophillus spesies dan Pseudomonas
spesies. Bayi yang baru lahir umumnya dibawa berobat karena menunjukkan gejala
kemerahan pada mata, pembengkakan kelopak mata atau mata lengket, atau disebabkan
keluarnya duh tubuh dari mata.

Manifestasi klinis dan mungkin komplikasi akibat infeksi gonokokus dan klamidiosis
umumnya memberikan gambaran yang mirip, sehingga sukar dibedakan. Pengobatan
harus mencakup kedua mikroorganisme penyebab tersebut, untuk gonore diberikan
dengan dosis tunggal dan untuk klamidiosis diberikan dosis terbagi.

Kotak 8.
PENGOBATAN SINDROM KONJUNGTIVITIS
NEONATORUM
Pengobatan BAYI
 Terlebih dulu diberikan pengobatan untuk gonore
Bila 3 hari tidak ada perbaikan DIIKUTI
 Pengobatan untuk klamidiosis

Pengobatan IBU
 Pengobatan untuk gonore tanpa komplikasi
DITAMBAH
 Pengobatan klamidiosis

Pedoman Nasional Penanganan Infeksi Menular Seksual 2015 | 47

Tabel 12. Pengobatan bayi dengan konjungtivitis neonatorum

PENGOBATAN KONJUNGTIVITIS GONORE PENGOBATAN KONJUNGTIVITIS KLAMIDIA

Seftriakson 50-100 mg/kgBB, injeksi Sirop eritromisin basa, 50 mg/kgBB/hari

intramuskular, dosis tunggal ATAU per oral, 4 kali sehari, selama 14 hari ATAU

Kanamisin 25 mg/kgBB (maksimal 75

mg), injeksi intramuskular, dosis tunggal
ATAU

Tabel 13. Pengobatan ibu dengan bayi yang menderita konjungtivitis neonatorum

PENGOBATAN SERVISITIS GONORE PENGOBATAN SERVISITIS NON-GONORE

Sefiksim 400 mg, dosis tunggal, per oral Azitromisin 1 g, dosis tunggal, per oral
ATAU ATAU

Doksisiklin* 2x100 mg/hari, per oral, 7

hari

Pilihan pengobatan lain

Kanamisin 2 g, injeksi IM, dosis tunggal Eritromisin 4x500 mg/hari, per oral, 7 hari
ATAU

Seftriakson 250 mg, injeksi IM, dosis

tunggal

* Tidak boleh diberikan kepada ibu menyusui; IM = intramuskular

48 | Pedoman Nasional Penanganan Infeksi Menular Seksual 2015

BAGAN 7. KONJUNGTIVITIS NEONATORUM DENGAN PENDEKATAN SINDROM

Pedoman Nasional Penanganan Infeksi Menular Seksual 2015 | 49

 Child Health Update
Treatment and prevention of ophthalmia neonatorum
Adela Matejcek MD  Ran D. Goldman MD FRCPC

Abstract
Question  In my office I occasionally see neonates with conjunctivitis. What are the current recommendations for
ocular prophylaxis at birth? Do topical antibiotics alone provide adequate treatment of neonatal conjunctivitis?
When is systemic therapy indicated?

Answer  All infants should receive ocular prophylaxis at birth to prevent gonococcal ophthalmia. Neonates
presenting with signs of conjunctivitis should have a conjunctival swab sent for Gram stain and culture. If
Gram-negative diplococci are present on the Gram stain results, the infants and their parents should be treated
immediately for presumed gonorrhea. Infants with chlamydial infection should be treated with oral antibiotics.
Most of all other forms of bacterial conjunctivitis can be treated with topical antibiotics, with the exception of
Pseudomonas infection. Infants should be followed during their treatment and upon completion of therapy to
ensure resolution of symptoms. For cases in which sexually transmitted bacteria are implicated, the mothers and
their sexual partners should be treated.

Traitement et prévention de la conjonctivite suppurée du nouveau-né

Résumé
Question  Je vois à l’occasion à mon cabinet des nouveau-nés atteints de conjonctivite. Quelles sont les
recommandations actuelles pour la prophylaxie oculaire à la naissance? Les antibiotiques topiques à eux seuls
sont-ils un traitement suffisant de la conjonctivite néonatale? Quand une thérapie systémique est-elle indiquée?

Réponse  Tous les nouveau-nés devraient recevoir une prophylaxie oculaire à la naissance pour prévenir la
conjonctivite gonococcique. Chez les nouveau-nés qui présentent des signes de conjonctivite, on devrait procéder
à un prélèvement conjonctival et l’envoyer pour une coloration de Gram et une culture. Si des diplocoques Gram
négatif sont présents dans les résultats de la coloration de Gram, le nouveau-né et ses parents devraient être
traités immédiatement pour une présumée gonorrhée. Les nouveau-nés atteints d’une infection aux chlamydias
devraient être traités avec des antibiotiques par voie orale. La plupart des autres formes de conjonctivite
bactérienne peuvent être traitées avec des antibiotiques topiques, à l’exception des infections aux Pseudomonas.
Il faudrait suivre les nouveau-nés durant leur traitement et à la fin de la thérapie pour s’assurer de la disparition
des symptômes. Dans les cas où des bactéries transmises sexuellement sont en cause, les mères et leurs
partenaires sexuels devraient être traités.

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C onjunctivitis is an inflammatory disease character-

ized by conjunctival erythema, swelling, and
discharge.1 Ophthalmia neonatorum (ON), also called
neonatal conjunctivitis, is an acute, mucopurulent
infection occurring in the first 4 weeks of life,2 affecting
1.6% to 12% of all newborns, 3,4 caused by chemical,
bacterial, or viral processes. 3 Before the 1880s, ON
was the primary cause of neonatal blindness and the
term ophthalmia neonatorum was used only for cases
of conjunctivitis due to Neisseria gonorrhoeae.5,6 In 1881,
Dr Carl Siegmund Franz Credé, a German obstetrician,
introduced ocular prophylaxis with 2% silver nitrate
at birth, which resulted in a dramatic reduction in the
incidence of neonatal gonococcal conjunctivitis from
10% to 0.3%.5,7 In recent years, there has been increasing
debate about the necessity of “Credé’s prophylaxis”
given that the prevalence of sexually transmitted
infections has declined, treatment of ON has improved,
and prophylaxis carries a certain risk of developing
antibiotic resistance. As a result, ocular prophylaxis has
fallen out of practice in some countries in the developed
world, which has led to the reemergence of sight-
threatening infections.8 In the current Canadian context,
the evidence supports that ocular prophylaxis should
remain the standard of care 5; however, debate and
controversy have emerged around this issue in Canada.9

Vol 59:  NOVEMBER • NOVEMbre 2013 | Canadian Family Physician • Le Médecin de famille canadien  1187
 Child Health Update
Causes of ON
Causes of ON include the following.
Chemical conjunctivitis. Chemical
conjunctivitis accounts for most
cases of ON,4 presenting as a mild,
purulent conjunctivitis within the
first 24 hours of life. It is most com-
monly associated with silver nitrate
prophylaxis, or secondary to pro-
phylaxis with other agents such
as erythromycin or tetracycline. 3
Chemical conjunctivitis is a self-lim-
iting condition that does not require
any diagnostic tests or treatment.10
Non–sexually transmitted bacte-
ria.  Non–sexually transmitted
bacteria account for 30% to 50%
of cases of ON. 5 The most com-
monly isolated microorganisms
are listed in Box 1. The role of
Staphylococcus aureus is unclear, as
it is commonly cultured from the
eyes of asymptomatic infants.1 Most
cases of bacterial ophthalmia can
be treated with topical antibiotics
(aminoglycosides, polymyxin B sul-
fate–trimethoprim solution, mac-
rolides, or fluoroquinolones). 1,3,11
Ophthalmia neonatorum caused
by Pseudomonas is rare but can
present with eyelid edema,
erythema, and purulent discharge
causing corneal perforation,
Box 1. Causes of
ophthalmia neonatorum
Causes of ophthalmia neonatorum
include the following:
Chemical
Bacterial
• Chlamydia trachomatis
• Neisseria gonorrhoeae
• Haemophilus species
• Streptococcus pneumoniae
• Staphylococcus aureus
• Staphylococcus epidermidis
• Streptococcus viridans
• Escherichia coli
• Pseudomonas aeruginosa
• Other
Viral
• Adenovirus
• Herpes simplex virus
1188  Canadian Family Physician • Le Médecin de famille canadien | Vol 59:  NOVEMBER • NOVEMbre 2013
endophthalmitis, blindness, and
possibly death.3,4 Presumptive diag-
nosis can be made from Gram stain
results, and a definitive diagnosis
is based on conjunctival culture
results.4 Systemic antibiotics have
poor penetration into the ante-
rior chamber of the eye, and thus
both systemic and topical amino-
glycoside antibiotics, and occasion-
ally subconjunctival injections, are
required for effective treatment.
These infants require isolation and
assessment by an ophthalmologist.3
Sexually transmitted bacteria
Chlamydia trachomatis:  Sexually
transmitted bacteria including
C trachomatis account for up to 40%
of all cases of ON in Canada.3,5 An
infant born vaginally to a mother
with chlamydial cervicitis has a
50% to 75% chance of acquiring the
bacteria in the nasopharynx, rec-
tum, vagina, or conjunctiva. 12 Of
neonates with proven exposure to
chlamydia, 30% to 50% will develop
conjunctivitis.13 The prevalence of
chlamydial infections is higher in
the spring and summer months. 14
The incubation period is typically
1 week after delivery; however, it
varies from 5 to 14 days or ear-
lier if membranes ruptured prema-
turely.15 The clinical manifestations
vary from mild conjunctival injec-
tion with scant watery discharge
to severe mucopurulent discharge
with eyelid edema, chemosis, and
pseudomembrane formation. 6,13
Loss of vision is very rare. Most
cases of chlamydial infections
resolve spontaneously without com-
plications, but, if left untreated,
superficial corneal vasculariza-
tion and conjunctival scarring can
occur. 13 Newborns with conjuncti-
vitis should have specimens of their
conjunctiva and pharynx sent for
culture. The American Academy of
Pediatrics recommends a 14-day
course of systemic erythromycin
(50 mg/kg/d, divided in 4 doses).16
Topical therapy is not indicated. 13
Erythromycin has a 10% to 20%

failure rate and thus some infants will require a second
or occasionally a third course of erythromycin.11 Parents
should be informed of the potential risk of pyloric ste-
nosis and counseled on monitoring.13 A small study has
demonstrated that a short course of oral azithromy-
cin (20 mg/kg once daily for 3 days) might be an effec-
tive treatment alternative; however, further studies are
needed.17 The infant’s mother and her sexual partners
should be treated for chlamydia.3
Neisseria gonorrhoeae:  Neisseria gonorrhoeae
accounts for less than 1% of all reported cases of
ON in Canada. 5 In the absence of adequate prophy-
laxis, 30% to 42% of infants born by vaginal delivery
to infected mothers will develop gonococcal ON.6 The
transmission rate is higher in mothers with concomi-
tant chlamydial infection. 18 Infants born to mothers
with known gonococcal infection should be treated
with a single parenteral dose of cefotaxime or ceftri-
axone.5,7 If left untreated, gonorrheal ON can lead to
corneal scarring, ulceration, panophthalmitis, and per-
foration of the globe within 24 hours. 7 The disease
typically presents with profound chemosis, edema
of the eyelids, and abundant purulent discharge that
might be blood-tinged from superficial hemorrhage
within 2 to 5 days of birth; however, it can mani-
fest up to 2 to 3 weeks after delivery.6,7 Infants with
gonorrheal ON should be hospitalized, treated with
frequent irrigation of the conjunctiva and intravenous
or intramuscular administration of ceftriaxone (25 to
50 mg/kg, to a maximum dose of 125 mg), and evalu-
ated for disseminated gonococcal disease (eg, arthritis,
sepsis, meningitis).1,3,4 The infant’s mother and her sex-
ual partners should be treated for gonorrhea.1
Viral conjunctivitis.  Viral conjunctivitis is most com-
monly caused by adenovirus and herpes simplex virus.1,6
Vol 59:  NOVEMBER • NOVEMbre 2013
Child Health Update
Infants with adenovirus ON might present with pete-
chial hemorrhage or occasionally with large subcon-
junctival hemorrhages.1 Lymphadenopathy is associated
with approximately 50% of cases of viral conjunctivitis.1
Infants with conjunctivitis caused by herpes simplex
virus might be diagnosed late, as they are commonly
treated empirically for chlamydial or gonococcal infec-
tion.6 Herpetic lesions on the borders of the eyelids are
common and present 6 to 14 days after birth.6 These
infants require diagnostic evaluation, including lum-
bar puncture, and assessment by an ophthalmolo-
gist. Treatment includes systemic acyclovir (60 mg/kg
in divided doses 3 times a day) for 14 days, coupled
with topical ophthalmic solution (ie, 1% trifluridine, 0.1%
iododeoxyuridine, or 3% vidarabine).16,19
Preventing conjunctivitis
The Canadian Paediatric Society recommends that ocular
prophylaxis with 1% silver nitrate, 0.5% erythromycin
ointment, or 1% tetracycline hydrochloride be given
to all newborns, including those born by cesarean
section, in the first hour after birth.5 It is important to
note that routine ocular prophylaxis does not prevent
chlamydial ON; and that although gonorrheal ON
has become relatively rare with the introduction of
ocular prophylaxis, it must continue to be considered,
given its high propensity to cause severe ocular
destruction and blindness.3 
Competing interests
None declared
Correspondence
Dr Ran D. Goldman, BC Children’s Hospital, Department of Pediatrics, Room
K4-226, Ambulatory Care Bldg, 4480 Oak St, Vancouver, BC V6H 3V4;
telephone 604 875-2345, extension 7333; fax 604 875-2414;
e-mail rgoldman@cw.bc.ca
References
1. Thanathanee O, O’Brien TP. Conjunctivitis: systematic approach to
diagnosis and therapy. Curr Infect Dis Rep 2011;13(2):141-8.
| Canadian Family Physician • Le Médecin de famille canadien  1189
Child Health Update
2. Normann EK, Bakken O, Peltola J, Andréasson B, Buhl S, Sigg P, et
al. Treatment of acute neonatal bacterial conjunctivitis: a comparison
of fucidic acid to chloramphenicol eye drops. Acta Ophthalmol Scand
2002;80(2):183-7.
3. Teoh DL, Reynolds S. Diagnosis and management of pediatric
conjunctivitis. Pediatr Emerg Care 2003;19(1):48-55.
4. Wagner RS, Aquino M. Pediatric ocular inflammation. Immunol Allergy
Clin North Am 2008;28(1):169-88.
5. Canadian Paediatric Society Infectious Diseases and Immunization
Committee. Recommendations for prevention of neonatal ophthalmia.
Paediatr Child Health 2002;7(7):480-8.
6. Zuppa AA, D’Andrea V, Catenazzi P, Scorrano A, Romagnoli C.
Ophthalmia neonatorum: what kind of prophylaxis? J Matern Fetal
Neonatal Med 2011;42(6):769-73.
7. Woods CR. Gonococcal infections in neonates and young children.
Semin Pediatr Infect Dis 2005;16(4):258-70.
8. Schaller UC, Klauss V. Is Credé’s prophylaxis for ophthalmia
neonatorum still valid? Bull World Health Organ 2001;79(3):262-3.
9. Darling EK. Is mandatory neonatal eye prophylaxis ethically justified? A
case study from Canada. Public Health Ethics 2011;4(2):185-91.
10. Chandler JW, Rapoza PA. Ophthalmia neonatorum. Int Ophthalmol
Clin 1990;30(1):36-8.
11. Pichichero ME. Bacterial conjunctivitis in children: antibacterial
treatment options in an era of increasing drug resistance. Clin Pediatr
(Phila) 2011;50(1):7-13. Epub 2010 Aug 19.
12. Rours IG, Hammerschlag MR, Ott A, De Faber TJ, Verbrugh HA,
de Groot R, et al. Chlamydia trachomatis as a cause of neonatal
conjunctivitis in Dutch infants. Pediatrics 2008;121(2):e321-6.
13. Hammerschlag MR. Chlamydial and gonococcal infections in infants
and children. Clin Infect Dis 2011;53(Suppl 3):S99-102.
14. Di Bartolomeo S, Mirta DH, Janer M, Rodríguez Fermepin MR,
Sauka D, Magariños F, et al. Incidence of Chlamydia trachomatis and
other potential pathogens in neonatal conjunctivitis. Int J Infect Dis
2001;5(3):139-43.
1190  Canadian Family Physician • Le Médecin de famille canadien | Vol 59:  NOVEMBER • NOVEMbre 2013
15. Darville T. Chlamydia trachomatis infections in neonates and young
children. Semin Pediatr Infect Dis 2005;16(4):235-44.
16. American Academy of Pediatrics. Chlamydia trachomatis. In: Pickering
LK, editor. Red book: 2012. Report of the Committee on Infectious
Diseases. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
p. 276-81.
17. Hammerschlag MR, Gelling M, Roblin PM, Kutlin A, Jule JE. Treatment
of neonatal chlamydial conjunctivitis with azithromycin. Pediatr Infect
Dis J 1998;17(11):1049-50.
18. Laga M, Plummer FA, Nzanze H, Namaara W, Brunham RC, Ndinya-
Achola JO, et al. Epidemiology of ophthalmia neonatorum in Kenya.
Lancet 1986;2(8516):1145-9.19. American Academy of Pediatrics.
Herpes simplex. In: Pickering LK, editor. Red book: 2012. Report
of the Committee on Infectious Diseases. Elk Grove Village, IL:
American Academy of Pediatrics; 2012. p. 398-408.
Child Health Update is produced by the Pediatric
Research in Emergency Therapeutics (PRETx)
Pediatric Research in Emergency Therapeutics
program (www.pretx.org) at the BC Children’s
Hospital in Vancouver, BC. Dr Matejcek is a member and Dr Goldman is Director of the
PRETx program. The mission of the PRETx program is to promote child health through
evidence-based research in therapeutics in pediatric emergency medicine.
Do you have questions about the effects of drugs, chemicals, radiation, or
infections in children? We invite you to submit them to the PRETx program by fax
at 604 875-2414; they will be addressed in future Child Health Updates.
Published Child Health Updates are available on the Canadian Family Physician
website (www.cfp.ca).
[Downloaded free from http://www.sudanmedicalmonitor.org on Sunday, April 21, 2019, IP: 180.241.75.246]

Review Article

An overview of neonatal conjuctivitis

Mohammed Abdulsalam,
M. Ibrahim, M. O. Asani
Department of Paediatrics, Aminu
Kano Teaching Hospital, Kano,
Nigeria
Abstract
Neonatal conjunctivitis has been recognized for several centuries and it is one of the
most common infections occurring in the 1st month of life and remains an important
cause of ocular morbidity of great health concern especially in developing countries.
This article attempts to review the current epidemiology, etiology, risk factors,
pathogenesis, investigations, and treatment and offer possible preventive measures to
avert this potentially crippling disease. Most epidemiological reports have focused on
gonococcal and chlamydial neonatal conjunctivitis because both are associated with
sexually transmitted diseases and are therefore of general public health importance.
The risk of conjunctivitis in newborns depends on frequencies of maternal infections,
prophylactic measures, circumstances during labor and delivery, and postdelivery
exposures to microorganisms. The etiological agents implicated as causes of Neonatal
conjunctivitis can be classified into chemical and infective. Laboratory studies used in the
diagnosis of neonatal conjunctivitis include smears, stains, cultures, and serological tests.
Current World Health Organisation (WHO) guidelines for the management of sexually
transmitted infections recommend that all cases of neonatal conjunctivitis be treated for
both Neisseria gonorrhoeae and Chlamydia trachomatis. Four levels of intervention can be
used to prevent childhood blindness and ocular morbidity from neonatal conjunctivitis.
These strategies may reduce the prevalence of sexually transmitted disease, which in turn
may reduce the risk to infants of exposure to agents that cause neonatal conjunctivitis.
Key words: Bacteria, maternal, neonatal conjunctivitis, risk factors

INTRODUCTION Neonatal conjunctivitis has been defined in various

Neonatal conjunctivitis has been recognized for several
centuries though case definition differed.[1,2] Neonatal
conjunctivitis was originally described in 1750 by
Quellmaz.[3] It is one of the most common infections
occurring in the 1st month of life and remains an important
cause of ocular morbidity of great health concern. Faal[4]
noted that there were an estimated one and a half million
blind children in the world in 1992 and every year about
half a million more became blind. In Africa between 1000
and 4000 children are blinded annually by conjunctivitis.[5]
Address for correspondence:
Dr. Mohammed Abdulsalam, Department of Paediatrics, Aminu Kano
Teaching Hospital, Kano, Nigeria. E‑mail: muhdpaed@yahoo.com
Access this article online
Quick Response Code:
Website:
www.sudanmedicalmonitor.org
ways by different authors.[6‑12] Neonatal conjunctivitis
according to Kolade et al.[13] is defined as the inflammation
of the mucus membrane lining the eyelid and covering
the eyeball in a newborn within the first 28 days of life
whereby Gram staining of an eye smear shows at least
one polymorphonuclear leukocyte per high power field.[13]
According to Klaus[7] conjunctivitis is defined as an infant
aged <30 days with clinical signs of redness and swelling
of the eyelids and palpebral conjunctiva, purulent eye
discharge, and one or more polymorph nuclear leukocytes
per oil immersion field of a Gram stain conjunctival smear.[7]
The WHOs working group on neonatal conjunctivitis
defined it as any conjunctivitis with discharge occurring
during the first 28 days of life.[8]
This is an open access article distributed under the terms of the Creative Commons
Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak,
and build upon the work non‑commercially, as long as the author is credited and the new
creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com

DOI: How to cite this article: Abdulsalam M, Ibrahim M, Asani MO.

10.4103/1858-5000.167868 An overview of neonatal conjuctivitis. Sudan Med Monit 2015;10:91-8.

© 2015 Sudan Medical Monitor | Published by Wolters Kluwer - Medknow 91

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Abdulsalam, et al.: An overview of neonatal conjunctivitis. Sudan Medical Monitor

EPIDEMIOLOGY
Neonatal conjunctivitis is a worldwide problem, and
although global incidence is not known, incidences of
1–24% have been reported from various regions of the
world.[7] Most epidemiological reports have focused on
gonococcal and chlamydial neonatal conjunctivitis. This
is because, both are associated with sexually transmitted
diseases and are therefore of general public health
importance. In neonatal conjunctivitis, the reservoir
of infection is the pregnant woman who has either
gonococcal or chlamydia infection. Neonates born to
such mothers have a high risk of contracting the disease
during delivery or in utero if there was prolonged rupture
of amniotic membranes. [14] In the United States of Figure 1: Structure of the eye as adopted from Encarta Encyclopaedia
America, the incidence of neonatal conjunctivitis ranges
from 1% to 2% depending on the socioeconomic status ciliary body, and iris is vascular while the innermost layer
of the area.[6] (the retina) is nervous. The fluid in the eye is divided by the
lens into vitreous humor (behind the lens) and the aqueous
A higher incidence of neonatal conjunctivitis exists in
humor (in front of the lens).[1] The lens itself is flexible
developing countries.[15] In Nairobi, Kenya the incidences
and suspended by ligaments which allow it to change shape
of gonococcal and chlamydia neonatal conjunctivitis were
so as to focus light on the retina which is composed of
40 per 1000 and 80 per 1000 live births, respectively. More
sensory neurones.[1]
than 50% of the newborns in Nairobi had concurrent
gonococcal conjunctivitis. [6] This high incidence of
The conjunctiva is a thin layer of mucous membrane
neonatal conjunctivitis in Kenya was attributed to high
which lines the eyelids and is reflected on the eyeball to
prevalence of sexually transmitted infections in pregnant
cover the anterior aspect of that organ until, at the limbus,
mothers and lack of eye prophylaxis in neonates at
where it becomes continuous with the superficial layer
birth.[6] The prevalence of gonorrhoea is high among
of the cornea. The conjunctiva has three divisions: The
antenatal attendees in African countries ranging from
palpebral/tarsal conjunctiva, which covers the posterior
4% to 15%.[8] A report from the Makerere Medical School,
surface of the eyelids, the ocular/bulbal conjunctiva
Kampala Uganda showed that 75% of the neonates
covering the anterior portion of the eyeball, and the fornix,
studied had gonococcal neonatal conjunctivitis, although
the actual incidence was not stated in the report.[16] Kenya the transitional portion forming a fold between the eye lid
had a higher prevalence of 23.2% in the preprophylactic and the eyeball.[19]
era.[17] However, the prevalence reduced to 17.6% after
The bulbar conjunctiva is thin and transparent, covers
silver nitrate, 15.2% after erythromycin, and 13.3% after
the anterior surface of the eyeball and is loosely attached
povidone iodine prophylaxes were introduced.
to the sclera by a connective tissue, the episclera, except
In Nigeria, a survey of neonatal conjunctivitis in Benin near the limbus where it becomes firmly adherent. Near
city with emphasis on gonococcal neonatal conjunctivitis the inner canthus, it forms a crescentic fold called the
showed an incidence of 8.9 per 1000 live births.[18] A similar plicasemilunaris  (representing the 3rd eyelid in lower
study from Zaria by Ugbode[14] showed a prevalence of vertebrates).[19] The conjunctiva of the fornix constitutes a
2.7%. Another study from Ilorin by Kolade et al.[14] reported loose fold, ensuring freedom of movement to the eyeball.
a prevalence of 13.5%. Its epithelium, unlike the bulbal conjunctiva, contains three
layers of cells. It is richly supplied with blood vessels. The
ducts of lacrimal glands open onto it.[19]
THE STRUCTURE AND FUNCTION OF THE
EYE Mechanical factors such as blinking of the eyes lead
to irrigation of the eyes by tears which protect the
Anatomically and functionally, the eye [Figure 1] is the conjunctiva from physical trauma and also reduce the
organ of sight, a hollow globe filled with fluid (humor). duration of contact with infecting or irritating agents.
The outer layer comprising the sclera and cornea is fibrous The tear fluid is endowed with antibacterial properties
and protective. The middle layer composed of the choroids, like lysozymes and immunoglobulin A  (IgA). Specific

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Abdulsalam, et al.: An overview of neonatal conjunctivitis. Sudan Medical Monitor
antibodies are produced and may be detected in the tears,
but their concentration is not known to be related to the
outcome of conjunctivitis.
The conjunctiva of a neonate is sterile at birth but soon
becomes colonized by various microorganisms that may
either be pathogenic or nonpathogenic.[20] The conjunctiva
is prone to infection not only because there are low levels
of antibacterial agents and proteins like lysosomes and IgA
and G, but also because the tear film and flow are only just
beginning to develop.[17,21] Contamination of the baby’s
eyes with microorganisms from the mothers’ genital tract
or from the hands of birth attendants serves as a mode of
acquiring neonatal conjunctivitis.[22]
ETIOLOGY
The etiological agents implicated as causes of neonatal
conjunctivitis can be classified into chemical and infective.
The infective agents include viruses, fungi, and bacteria.[23]
Bacterial agents implicated in ophthalmia neonatorum include
Neisseria gonorrhoeae and Chlamydia trachomatis.[24,25] Other
major causative bacterial agents includes Staphylococcus aureus,
Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus
influenza, and Pseudomonas aeruginosa.[26] In a study by Jones
and Barbara,[27] Mycoplasma hominis was isolated from 8 out of
250 clinically infected eyes of newborn infants.[27] Robert,[28]
have reported an outbreak of adenoviral conjunctivitis in
a neonatal intensive care unit affecting seven premature
infants who 4–7 days earlier had undergone examination for
retinopathy of prematurity. Most infants acquire the herpes
simplex infection during the birth process.[13] Fungi such as
Candida albican have been reported to cause conjunctivitis
in the neonatal period.[6] The conjunctivitis is usually part
of an Endophthalmitis resulting from candidemia and is
now well recognized especially in very low birth weight
preterm neonates.[14]
Aseptic neonatal conjunctivitis is most often a chemical
conjunctivitis that results from a reaction to the prophylactic
agent instilled into the eye at birth to prevent bacterial
ophthalmia neonatorum.[10] It is most commonly induced
by silver nitrate solution which was found to be an irritant
to the conjunctiva.[2,7] It has been reported to occur in
10–00% of treated neonates during the first 24  h of
life and presents as a mildly purulent conjunctivitis that
usually resolves within 48 h.[10] Other topical prophylactic
agents used such as silver acetate and quaternary
ammonium compound like benzethonium chloride, have
not been studied extensively. Recently, povidone iodine
2.5% has been used and has not been documented to
produce irritation.[29] In some cases, etiology of neonatal
Sudan Medical Monitor | July - September 2015 | Vol 10 | Issue 3 93
conjunctivitis remains obscure.[23,30] Several studies have
documented cases of clinical conjunctivitis, with no
organisms isolated. In a study by Prentice et al.,[31] 53.5%
cases with conjunctivitis had no microorganism isolated
and they proposed chemical irritation and/or unidentified
microbial agents either bacterial or viral as possible causes.
PATHOGENESIS
The pathogenesis of gonococcal and chlamydia ocular
infections in the newborn are well documented but that
due to other causes is still obscure.[7] Neonates acquire the
gonococcus either in utero, during delivery or postnatally
from medical personnel, contaminated objects in the
delivery room or nursery or other individuals in the family
or by autoinoculation from other infected sites.[32] The
organism also known to colonize other systems leading to
septicaemia in the neonate. The association of amniotic
infection syndrome and recovery of gonococci in the
orogastric aspirates has been described by Blank in 1959.[33]
Recovery of gonococci from orogastric aspirates of the
neonate reflects contamination of the upper gastrointestinal
tract, upper respiratory tract, and probably the lower
respiratory tract. There is good reason to believe that this
can cause infection in the neonates.
The involvement of the cornea can be severe and first
appears as a diffuse corneal edema which gives the cornea
a hazy appearance while opacities appear around the
corneoscleral junction.[8] When new blood vessels invade
the cornea scarring may result, ulceration and perforation
of the globe may ensue. This occurs in untreated
cases around the 3rd  week. The gonococcus which is a
Gram‑negative intracellular diplococcus exhibits four
morphologic types of colonies.[18] Only 1 and 2 appear to be
virulent and possess pili which attach to epithelial cells and
help to resist phagocytosis.[34] Gonococci contain several
plasmids (molecular weight 4.5 × 10) which carry the gene
for B‑lactamase production.[34] These make the gonococci
resistant to penicillins. These plasmids are transmissible
among the gonococci and are acquired from Haemophilus
or other Gram‑negative organisms.[34] Gonococci attack
mucous membranes of the eye and genital tract, producing
within 1 and 3  days acute suppuration that may lead to
tissue invasion by polymorph nuclear leucocytes. This may
result in chronic inflammation and fibrosis.[34] gonococcal
bacteremia leads to skin lesions especially hemorrhagic
papules and pustules, arthritis, tenosynovitis, especially
of the knees, ankles, and wrists. Other lesions include
proctitis, pharyngitis, myopericarditis, and endocarditis.[35]
Lasting immunity does not seem to develop in the course
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Abdulsalam, et al.: An overview of neonatal conjunctivitis. Sudan Medical Monitor
of gonococcal infections, although IgA antibodies occur
on mucous membranes.[34] Reinfection is a common
occurrence.
The pathogenesis of chlamydial infections has been studied
in detail by several workers.[8,34,36] Chlamydial neonatal
conjunctivitis is caused by C. trachomatis serotypes D to K,
which are the same serotypes that cause genital infections
in man.[34] It is a Gram‑negative Bacillus with an incubation
period of 5–14 days.[8] The fact that the neonate acquires
the organism from the maternal cervix during delivery
has been substantiated by various workers.[37,38] Rees et al.
studied 103 babies with conjunctivitis, 33 of whom had a
chlamydia infection.[37] About 66% of their mothers had
chlamydia isolated from their cervix.[37] Transmission rates
from mother to baby has been calculated in various studies
and ranged from 28% in studies by Heggie et al.[38]
PERIOD OF OUTSET
Chemical conjunctivitis secondary to silver nitrate solution
application usually occurs on the 1st day of life, disappearing
spontaneously within 2–4 days.[6] Meconium or other
irritants have similar effects on the conjunctiva. Gonococcal
neonatal conjunctivitis tends to occur 3–5 days after birth,
but can present later especially if topical prophylaxis has
been used.[6] A study by Hansfield et al. reported that the
incubation period ranged from 1 to 21 days, and purulent
discharge occurred in 81% and was mostly bilateral.[33] In
another study at the Liverpool Royal Imfirmary, the onset
of eye discharge was 1–8 days.[37] while in one case report
from Lagos, Nigeria, the baby presented with foul smelling
bilateral and purulent eye discharge at birth.[39]
Chlamydia conjunctivitis usually has a late onset than
gonococcal conjunctivitis. Incubation period of 5–14 days
after delivery[6] was reported with approximately 50% being
bilateral.[6] The Incubation period for nongonococcal
nonchlamydial conjunctivitis is longer. [40] Herpetic
conjunctivitis usually occurs during a first 2 weeks after
birth.
CLINICAL FEATURES
Significant overlap in clinical presentations of neonatal
conjunctivitis may be present.[6] The clinical features of
neonatal conjunctivitis may range from mild stickiness
to conjunctival hyperemia, purulent eye discharge, and
significance eyelid edema.[6] The severity of presentation
depends on the infective organism. [22] Sandstorm [40]
proposed that there are three clinical presentations that
may suggest the etiology of neonatal conjunctivitis.
These include purulent eye discharge, edema of the
94
eyelid, and hyperemia of the conjunctiva. Noninfective
causes may produce hyperemia and trauma may cause
swelling of the eyelid making the diagnosis difficult in
these circumstances.[40]
Gonococcal neonatal conjunctivitis tends to be severer
than other causes; there is a classic presentation of purulent
conjunctivitis which is usually bilateral.[6] There may be
corneal involvement including diffuse epithelial edema
and ulceration that may progress to perforation of the
cornea and Endophthalmitis.[6] The patient may also have
systemic manifestations such as; rhinitis, stomatitis arthritis,
meningitis, anorectal infection, and septicaemia.[6] The
clinical features of chlamydial neonatal conjunctivitis may
range from mild hyperemia with scanty mucoid discharge to
eye swelling, chemosis, and pseudomembrane formation.[6]
Blindness though rare and slower in onset than in gonococcal
neonatal conjunctivitis is due to eyelid scarring and pannus
formation.[6] Follicular reaction does not occur because
newborns have no lymphoid tissue in the conjunctiva.[6]
Chlamydial neonatal conjunctivitis may also be associated
with extraocular involvement such as pneumonitis, otitis
media, pharyngeal, and rectal colonization.[6] Herpes
simplex keratoconjunctivitis usually present in infants with
generalized herpes simplex infection.[2] Serious systemic
complications such as encephalitis may occur due to poor
immunologic response.[6]
LABORATORY DIAGNOSIS
Laboratory studies used in the diagnosis of neonatal
conjunctivitis include smears, stains, cultures, and
serological tests.[41] Growth of commensal organisms
can be prevented by the use of selective culture media
which inhibit the growth of commensals but support the
growth of pathogens suspected of causing the infection.[42]
Contaminants or commensals can also be differentiated
from pathogenic organisms by morphological appearance,
biochemical tests, and enzymes production.[42] Criteria for
the identification of the organisms include: (a) Macroscopic
appearance  (b) microscopic appearance involving the
Gram staining properties which can be Gram‑positive
or negative (c) culture methods and (d) biochemical tests
including catalase, coagulase, urease, citrate, triple sugar
inhibition, and sugar fermentation tests.[42] A smear of
specimen for microscopic study is prepared by rolling a
small quantity of the specimen material across a glass slide.
Serological tests are used for detection of immunological
response to infective agents.[41] For most pathogens,
detection of IgM antibodies or a fourfold increase
in the patient’s antibody titre is diagnostic of current
infection.[41] Other techniques include direct fluorescent
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antibody. [43] and antigen immunochromatographic
test. [44] The immunochromatographic test has been
found to have an acceptable sensitivity (83.5%) and good
specificity (98.9%) compared to molecular testing.[44]
Nucleic acid amplification test  (NAAT) is currently
the standard method for detection of chlamydia where
facilities exist.[44] The test finds the genetic material (DNA)
of chlamydia and is the most sensitive test available.
It is very accurate and unlikely to have false positive
result. Polymerase chain reaction is an example of this
test (NAAT). The advantage of this test is that it is generally
more sensitive and specific than conventional culture and
can, therefore, identify positive specimens.[44]
TREATMENT
Current WHO guidelines for the management of sexually
transmitted infections recommend that all cases of
neonatal conjunctivitis be treated for both N. gonorrhoeae
and C. trachomatis.[45]
Neonatal conjunctivitis due to Neisseria gonorrhoeae
Treatment of gonococcal conjunctivitis consists of
intravenous Penicillin G 100,000 units/kg/day for 1 week.
N. gonorrhoeae isolates are resistant to penicillin in many
areas. Across Africa, rates of penicillinase producing
N. Gonorrhoeae range from 18% to 57% and other parts
of the world  (50–60%).[46] Hence, a third generation
cephalosporin drug should be used for 7 days in areas
where penicillinase producing strains are endemic. A single
dose of ceftriaxone 50 mg/kg as a single dose (maximum
125  mg) is highly effective and recommended by
WHO guidelines.[47,48] Alternative medications include
spectinomycin 25  mg/kg  (maximum 75  mg) as single
intramuscular dose and kanamycin 25 mg/kg (maximum
75  mg.[49] Infected mothers should also be treated with
single dose of ceftriaxone  (25–50  mg/kg). The infant’s
eyes should also be frequently irrigated with normal saline
to eliminate the discharge.
Neonatal conjunctivitis due to Chlamydia trachomatis
W H O a n d A m e r i c a n A c a d a my o f Pa e d i t r i c s
recommendations include oral erythromycin 50 mg/kg/day,
in 4 divided doses for 14 days.[50] Topical erythromycin or
tetracycline can be used as an adjunt therapy. The advantages
of oral erythromycin include eradication of nasopharyngeal
carriers, treatment of associated pneumonitis and also
being more effective than topical in preventing relapse
of conjunctivitis. Infected partners should receive oral
doxycycline 100 mg twice daily for 7 days or azithromycin
1 g orally as a single dose.[45]
Sudan Medical Monitor | July - September 2015 | Vol 10 | Issue 3 95
Nongonococcal nonchlamydial neonatal conjunctivitis
Preliminary presumptive treatment pending culture
confirmation should be based on clinical suspicion.
Therapy can be modified when results of culture and
sensitivity are known. Empirical treatment should include
erythromycin ointment and intravenous or intramuscular
third generation cephalosporin. [51] Erythromycin or
bacitracin ointment can be used for conjunctivitis due to
Gram‑positive organisms while gentamicin or tobramycin
drops are used for Gram‑negative bacterial organisms.[51]
Neonatal conjunctivitis due to Herpes simplex and chemical
conjuctivitis
Herpetic neonatal conjunctivitis should be treated with
systemic acyclovir to reduce the chance of a systemic
infection. The effective dose is 30 mg/kg/day intravenously
in 3 divided doses.[52] The duration of therapy ranges from
14 to 21 days. Neonates with herpes simplex viral keratitis
should receive a topical ophthalmic drug like 1% trifluridine
drops or 3% vidarabine.[52]
Chemical conjunctivitis usually requires no treatment;
however lubrication with artificial tear preparation may
ease discomfort.[6]
PREVENTION
Four levels of intervention can be used to prevent
childhood blindness and ocular morbidity from neonatal
conjunctivitis. [53] The first involves the prevention
of sexually transmitted diseases. The emergence of
infection with human immunodeficiency virus has led
to health promotion programs concerned with sexual
behavior (promoting monogamous relationships and use
of barrier contraceptives). These strategies may reduce the
prevalence of sexually transmitted disease, which in turn
may reduce the risk to infants of exposure to agents that
cause neonatal conjunctivitis.[53]
The second approach consists of antenatal screening.
Neonatal conjunctivitis can be prevented by screening
pregnant women for genital infection, particularly those
at high risk for the disease. Women with culture positive
infections and their partners require adequate systemic
treatment with follow‑up throughout pregnancy and
delivery.[53]
The third approach is ocular prophylaxis at birth, which
is simple and inexpensive.[53] It consists of cleaning an
infant’s eyelids with a dry swab as soon after birth as
possible and then instilling a safe, available, and affordable
antimicrobial agent.[53] Under the British Columbia Health
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Abdulsalam, et al.: An overview of neonatal conjunctivitis. Sudan Medical Monitor
Act Communicable Disease Regulation (1995), a physician,
midwife, or other qualified person assisting at birth of a
baby must within 1 h of birth treat the eyes of the baby with
a prophylactic solution of 1% tetracycline hydrochloride,
0.5% erythromycin, or 1% silver nitrate dispensed in
single‑use containers.[54‑56] Isenberg et al.[5] reported on the
use of a 2.5% solution of povidone‑iodine as prophylaxis
against neonatal conjunctivitis. It has in vitro activity against
a wide spectrum of bacteria, including chlamydia, and
some viruses. Its use as a topical ocular antimicrobial agent
appears promising particularly in developing countries.[5]
For very premature babies whose lids are fused at the time
of birth, apply the prophylactic agent without separating
the eyelids.[57] when 1% tetracycline or 0.5% erythromycin
is used, a line of ointment 1–2 cm long is placed in each
lower conjunctival sac, if possible covering the whole lower
conjunctival area. Gently massage the closed eyelids to help
spread the solution to all areas of the conjunctiva.[55] when
1% silver nitrate is used, two drops of solution are placed
in each lower conjunctival sac, a single ampoule being
used for each eye. Primary caregivers need to be informed
that transient chemical conjunctivitis may occur.[55] After
1  min, any excess ointment or drops should be gently
wiped from the eyelids and surrounding skin with sterile
cotton.[56] the eyes should not be irrigated after instillation
of a prophylactic agent.[55,58]
Finally, early diagnosis and adequate treatment of neonatal
conjunctivitis can prevent corneal ulceration and blindness.
The WHO vision 2020 “The Right to Sight, Global
Initiative for the Elimination of avoidable Blindness”
is highly committed to the control of blindness in
children.[25] In order to eliminate childhood blindness due
to neonatal conjunctivitis, an interdisciplinary approach
is required involving gynecologists, neonatologists,
ophthalmologists, and most important all primary health
care workers.[53] Those at the greatest risk are infants born
to mothers from areas with a high prevalence of sexually
transmitted disease and limited availability of topical
ocular antimicrobial agents.[53] All primary health care
workers should be educated about the cause, prevention,
and treatment of neonatal conjunctivitis. With increased
awareness of the disease, ready availability and widespread
use of a suitable prophylactic agent and appropriate
treatment when needed, neonatal conjunctivitis will not
lead to blindness.[53]
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
96
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98 Sudan Medical Monitor | July - September 2015 | Vol 10 | Issue 3

 UpdatelLe point
Epidemiology and control of
gonococcal ophthalmia neonatorum*
M. Laga,' A. Meheus,2 & P. Piot'

From a public health point of view gonococcal ophthalmia neonatorum (GCON) is important as it can rapidly
lead to blindness. The frequency of GCON is determined by the prevalence of maternal gonococcal infection.
In most industrialized countries the prevalence of gonorrhoea in pregnant women is less than 1 %;
in developing countries the rates are between 3% and 15%, more than 50% being due to penicillinase-
producing Neisseria gonorrhoeae strains (PPNG). The rate of transmission from mother to newborn is
between 30% and 50%.
Strategies for the control of GCON include: (1) prevention of gonococcal infection in women of
childbearing age, (2) detection and treatment of gonococcal infection in pregnant women, (3) eye prophylaxis
in the newborn at birth, and (4) diagnosis and treatment of GCON. Eye prophylaxis by the instillation
immediately after birth of either 1% silver nitrate eye drops or 1% tetracycline eye ointment is very effective.
This reduces the GCON incidence by 80% to 95% and is highly cost-effective, particularly in high-risk
settings.

Epidemiology gonorrhoeae accounted for the majority of cases seen

Disease manifestation
Ophthalmia neonatorum (ON) is defined as a purulent
conjunctivitis in infants less than 30 days old, where
the Gram stain of an eye smear shows at least one
polymorphonuclear leukocyte per high-power field.
Of the many causes, the two main ones are Neisseria
gonorrhoeae and Chlamydia trachomatis. Although
there are different patterns of disease, the manifesta-
tions produced by any one agent are not sufficiently
distinctive to lead to an etiologic diagnosis from the
clinical signs alone.
Gonococcal ophthalmia neonatorum (GCON)
tends to appear earlier and to be more severe than the
chlamydial infection. Differences in the incidence of
ON, by etiology, obtained in Nairobi from a cross-
sectional clinic-based study and a population-based
cohort study are shown in Table 1; C. trachomatis was
the most frequently identified cause when 1019 mother-
infant pairs were followed up for 1 month, while N.
r A resume of this article in French appears on pages 476-477.
Department of Microbiology, Institute of Tropical Medicine, Antwerp,
Belgium.
' Programme of Sexually Transmitted Diseases, World Health
Organization, 1211 Geneva 27, Switzerland. Requests for reprints
should be sent to this author.
Reprint No. 5001
Bulletin of the World Health Organization, 67 (5): 471-478 (1989)
at the sexually transmitted diseases (STD) clinic.
GCON begins between 1 and 13 days from birth and is
mostly bilateral and purulent, the conjunctivae and
eyelids being oedemic and hyperaemic. If untreated,
diffuse epithelial oedema of the cornea gives it a hazy
greyish appearance. Coarse white opacities (infiltra-
tions) appear near the border of the cornea and the
sclera, and can enlarge and become ulcerated by the
end of the second or third week. These ulcerations can
lead to perforation of the eyeball with loss of vision.
When new blood vessels invade the cornea, corneal
scarring may occur. The initiation of effective treat-
ment dramatically changes the course and outcome of
the disease, usually with recognizable improvement
within 24 hours.
It is difficult to estimate the risk of blindness
associated with gonococcal ophthalmia. In 1880, over
a hundred years ago, in Stuttgart the incidence of
GCON varied from 1% to 14% and 20-79% of
children in institutions for the blind had a history of
GCON. After introduction of ocular prophylaxis at
birth, GCON dropped dramatically and the per-
centage of institutionalized children whose blindness
was caused by GCON steadily declined. At present, in
many developing countries the incidence of GCON is
still high although blindness in children is not reported
to be highly prevalent; however, since blind children
World Health Organization 1989 471
M. Laga et al.

Table 1: Comparison of the Incidence and etiology of ophthalmia neonatorum (ON) In Nairobi from a cohort study and
clinic-based survey'

Cohort studyb
Cross-sectional study:c
Percentage percentage
Incidence per of all ON of all ON

100 live births (n= 181) (n= 149)

Gonococcal ophthalmia 2.8 12% 43%

Chlamydial ophthalmia 7.3 32% 13%
Gonococcal and chlamydial
ophthalmia 0.8 3% 4%
Non-gonococcal,
non-chlamydial ophthalmia 12.3 53% 40%

Total 23.2

' Data from references/10 and 17. q : £

bCohort of 1019 mothers and infants followed up for the first month of life.
a
c Survey of Infants with ON presenting at the sexually transmitted diseases clinic in Nairobi.

have a higher mortality rate, the true extent of the
problem would not be apparent in prevalence surveys.
In a clinic-based study on 64 neonates with GCON,
16% proved to have corneal involvement (10). It is not
yet clear which factors are responsible for a more
fulminant course of disease; virulence of some strains
or unusual susceptibility of the host, e.g., cases among
premature babies, have been suggested.
Gonococcal Infections
Prevalence In pregnant women. Data on the prevalence
of gonorrhoea among women receiving antenatal care
Table 2: Prevalence of gonococcal Infections among pregnant women worldwide
Place No. tested
give an estimate of the potential complications in
puerperal women and neonates. Table 2 summarizes
the prevalence of gonorrhoea in pregnant women from
surveys in different countries. The reported prevalence
from the USA shows wide geographical variations
ranging from 0.6% to 7.6% in the different popula-
tions studied. Generally, much higher prevalence rates
were observed in populations in the USA than in other
industrialized countries where they are usually below
1%. In most African countries the prevalence rates
among antenatal clinic patients range from 3% to as
high as 22%. The few published results from other
Gonococcal
cervical infection (%) Year/reference

Africa:
Cameroon: Yaounde 296 14 1984/11
Rural area 22
Gabon: Masuku' 530 5.5 1984/29
Gambia: Bakau 6.7 1984/19
Ghana: Accra 148 3.4 1985/3
Kenya: Nairobi 3751 6.5 1986/17
South Africa: Bloemfontein 1200 11.7 1986/28
Zambia: Lusaka - 11.2 1986/14
Asia:
Malaysia: Kuala Lumpur 744 0.54 1981/12
Europe:
Norway: Trondheim 686 0.3 1986/24
United Kingdom: Cardiff 625 0.16 1975/25
Glasgow 1000 0.2
Newcastle 311 0
USA:
Minnesota 6464 2.7 1978/8
San Francisco 6854 0.6 1987/26
Seattle 543 2 1986/13
New York 1082 2.6 1985/20

Formerly called Franceville.

472
 Epidemiology and control of gonococcal ophthalmia neonatorum

continents suggest that some but not all countries have
a prevalence rate similar to that in Africa.
Since the mid-1970s, worldwide dissemination
of penicillinase-producing N. gonorrhoeae (PPNG)
strains and of strains with chromosomally-mediated
penicillin and tetracycline resistance increased progres-
sively. The proportion of gonococcal infection due to
PPNG strains is summarized in Table 3, which shows
the need for new approaches to gonorrhoea therapy.
Transmlialon rate from mother to baby. The neonate
acquires GCON during delivery through the infected
birth canal. Occasionally the disease has been trans-
mitted to infants delivered by Caesarian section after
prolonged rupture of the membranes (27)
The transmission rate from mother to child in the
absence of ocular prophylaxis has been estimated in
two prospective studies in Africa (Table 4). In Kenya
(Nairobi) GCON developed in 28 out of 67 babies
whose mothers had N. gonorrhoeae infections, a trans-
mission rate of 42% (seven babies were lost for
follow-up), while in Cameroon, 30% of exposed babies
(12/40) developed GCON; the incidence rates are
therefore 3.6 and 4 per 100 live births, respectively.
These incidence rates are very high, compared with
those from Western countries (average, 0.06%). Asymp-
tomatic carriage of N. gonorrhoeae in the eyes with
minimum inflammation has been described (23). In the
above-mentioned studies from Africa no children were
Table 3: Percentage of gonococcal infetion due to penicil-
ilnase-producing N. gonorrhoeae (PPNG) In various coun-
tries
Country PPNG strains (%) Year/Reference
Belgium 6 1986/15
Netherlands 11 1986/7
United Kingdom 2 1985/1
USA 0.5 1982/6
Kenya 55 1986/17
Zambia 41 1986/14
Rwanda (Kigali) 51.9 1984/4
Tanzania (Dar es Salaam) 19.2 1984/21
identified with an asymptomatic gonococcal infection
in the eyes.
The study from Kenya demonstrated that the
transmission rates of PPNG and non-PPNG strains
were similar. When the mother is infected with both
N. gonorrhoeae and C. trachomatis at the same time,
the gonococcal transmission rate to the newborn is
significantly higher (68% instead of 31%, P<0.01)
(17). This study also showed that postpartum endo-
metritis in the mother was a significant risk factor for
GCON which may be explained by differences in
pathogenicity of the strains, by both conditions arising
from maternal chorioamnionitis, or by factors protect-
ing the mothers against postpartum upper genital tract
infection which might also protect the newborns
against ocular infection.
Conjunctival infection is the commonest clinical
form of N. gonorrhoeae infection in the newborn, but
the mucous membranes ofthe vagina, the pharynx, the
rectum and the ear canal may also be colonized.
Isolation rates of N. gonorrhoeae from the pharynx in
neonates with gonococcal ON range from 7% to 15%
(10, 17). The transmission rate of N. gonorrhoeae from
the maternal cervix to extraocular sites has never been
determined in the absence of GCON and the natural
history ofextra-ocular gonococcal infection is unclear.
The possibility of extra-ocular colonization of N.
gonorrhoeae in infants with gonococcal ON has thera-
peutic implications and GCON should therefore always
be treated systemically.
Strategies for control
Four different strategies are available for controlling
GCON in neonates.
(1) Primary prevention
Pregnant and non-pregnant women (or their partners)
who are at risk can protect themselves from acquiring
gonococcal infections through behavioural modifica-
tion and/or the use of barrier contraceptives. Primary
prevention has not generally been successful in the

Table 4: Prevalence of maternal gonococcal Infections and transmission rate from mother to child In the absence of ocular
prophylaxis
No. of neonates Transmission Incidence per
Place and reference Prevalence (%) presenting with GCON rate (%) 100 live births

Kenya (Nairobi) (17) 7 (67/1019)' 28 42b 3.6

Cameroon (Yaound6) (11) 14 (40/296) 12 30 4

' Figures in parentheses indicate the No. of women infected/No. of women screened.
b This figure is a minimal estimate since 7 out of 67 newborns were lost for follow-up; the real transmission rate ranges between 42% and
52%.
473
M. Laga et al.
control of STD in the past, but the increase in
incurable viral infections that are transmitted sexually,
such as AIDS, may renew interest in primary preven-
tion of STD.
Data demonstrating a reduction in the prevalence
of gonococcal infections in women as a result of
behavioural change and condom use are not yet
available.
(2) Screening/case-fInding and treatment of gono-
coccal Infections during pregnancy
There are two basic approaches for early detection
and/or treatment depending on the availability of
laboratory services and resources: (a) identification of
the infection through laboratory confirmation (mass
screening or selective screening), and (b) mass treat-
ment (indiscriminate or selective) without laboratory
confirmation.
* MN" screning. Unfortunately countries with the
highest prevalence of infection, and thus the greatest
need for detection programmes are in general those
that are the least able to afford and perform screening.
Routine screening for gonococcal infections in preg-
nancy has been abandoned in many European coun-
tries (because of very low prevalences), but is still
practised in the USA. It has not yet been introduced in
most developing countries because of lack of diagnos-
tic facilities. The minimum prevalence necessary for
a cost-effective screening programme has not been
defined, but considering the preventable maternal and
neonatal complications, it would probably be low
(about 1%). Another complication is that women at
high risk for gonococcal infections often do not attend
antenatal care.
The best way for laboratory diagnosis of gonor-
rhoea is by culture, but a cheaper alternative is direct
microscopic examination of a Gram stain of the
cervical discharge. The latter is not a very valid test, the
positive predictive value in cases where the prevalence
of gonococcal infections in women is 5%, 15%, and
25% being 29%, 47% and 63%, respectively. Thus the
use of Gram-stain screening is only advocated in areas
with a high prevalence of gonococcal infections in
women (> 15%).
* Selectve screening. The cost-effectiveness of screen-
ing programmes can be increased by concentrating on
high-risk groups. These groups can be defined by
epidemiologic risk profiling, presence of symptoms, or
presence of clinical signs of cervicitis.
In a series of 1000 pregnant women in Nairobi,
being single and residing in certain areas were risk
factors for gonococcal infection (17).
474
* Nma treatment. Mass treatment would be indicated
only if it was shown to be more cost-effective than early
detection programmes, or if detection is impossible.
Since in many areas the prevalences of gonococcal
infections in pregnant women exceed 5% (see Table 2),
indiscriminate mass treatment could be the most
effective strategy if all maternal and perinatal com-
plications resulting from maternal gonococcal infec-
tions are taken into account.
Although the two above-mentioned strategies are
complex, expensive and operationally very difficult,
they offer benefits besides lowering the incidence of
GCON, such as reducing other complications (post-
partum endometritis) related to N. gonorrhoeae. Rates
of reinfection should be examined in order to assess
the need for repeated mass treatment or inclusion of
sex partners. Selected treatment regimens should be
evaluated for efficacy, development of resistance (in
areas with high proportions of PPNG), side-effects,
and cost.
(3) Ocular prophylaxis at birth
The transmission of N. gonorrhoeae from the maternal
cervix to the newborn's eyes can be interrupted by the
use of eye drops or ointment immediately after birth.
Three different regimens have been recommen-
ded: silver nitrate, 1% eye drops; tetracycline, 1% eye
ointment; and erythromycin, 0.5% eye ointment. Only
the first two have been evaluated prospectively in areas
with a high proportion of multiresistant gonococcal
strains, including penicillinase-producing N. gonor-
rhoeae. The results from Kenya demonstrated equal
efficacy of silver nitrate drops and tetracycline oint-
ment in the prevention of GCON, the attack rate
among exposed newborns given silver nitrate and
tetracycline being 7% and 3%, respectively (Table 5).
These findings are consistent with risk estimates of
transmission from mother to child when prophylaxis
was given (2, 27).
In the other studies (all retrospective) on the
efficacy of the three regimens in preventing GCON, the
prevalence of gonococcal infections in the mother was
often unknown and the expected rate of GCON was
too low to discern any protective effect.
Among the many explanations for the failure of
ocular prophylaxis to prevent neonatal ophthalmia
are acquisition of infection in utero following pro-
longed rupture ofmembranes, failure to instil the agent
directly into the conjunctival sac, flushing of the eye
after administration of silver nitrate (to prevent
chemical conjunctivitis), postpartum acquisition of
GCON either by autoinoculation or from other infec-
ted persons, and the failure to differentiate chlamydial
conjunctivitis from GCON.
Silver nitrate is cheap, but is toxic if overconcent-
 Epidemiology and control of gonococcal ophthalmia neonatorum
Table 5: Attack rates of GCON among exposed newborns reelving silver nitrate, tetracycline, and no prophylaxl'
Silver nitrate
Attack rates of GCON (%)C 7.0 (5/71)d
Efficacy compared to no
prophylaxis 83%
a Includes only exposed infants seen at follow-up visits; data from reference 18.
b Infants from a historical cohort.
c
The difference between the silver nitrate and tetracycline groups was 4.0% (95% confidence interval: -3.4 to 11.4).
d Figures in parentheses are the No. of newborns with gonococcal ophthalmia/No. of newborns exposed to N. gonorrhoeae.
rated (through bad preservation). Single-dose ampoules
are much more expensive and less easily available.
Tetracycline is nontoxic and may remain longer in the
eye because it is an ointment; multidose preparations
(which did not cause complications in the Nairobi
trial) are cheap and widely available in developing
countries. Erythromycin ointment is expensive and
not available in many poor countries.
It has been shown that a delay in prophylaxis of
more than 4 hours after birth is associated with
a 4-5-fold increase in risk of GCON (22). Prophylaxis
should therefore be given as soon after birth as
practical, preferably within one hour, for both hospital
and home births. Traditional birth attendants' kits
should include a single-dose dispensing system for eye
prophylaxis. There is no doubt that such prophylaxis
is operationally the most feasible strategy and the most
cost-effective approach ofthe four. In areas with a high
prevalence of gonococcal infections in pregnant women
prophylaxis at birth should be reinforced or (re)intro-
duced immediately as an initial step in the reduction of
neonatal morbidity related to STD in pregnancy.
(4) Diagnosis and treatment of GCON
Early diagnosis and appropriate treatment of gono-
coccal ophthalmia is important since the infection can
rapidly lead to blindness. The presence of a high
proportion of penicillin-resistant strains requires a
more expensive and less available treatment regimen
in many areas of the world.
Some countries with a low prevalence of gono-
coccal infections (e.g., Netherlands) have adopted the
strategy of diagnosis and treatment of GCON in the
newborns. The presence of neonatal infection is the
indicator for an infection in the parents, and screening
during pregnancy is not performed. In very low
prevalence areas, with good coverage of health services,
this strategy may be the most cost-effective, but has
never been evaluated systematically. Unfortunately, in
most countries where gonococcal infections are highly
prevalent, the diagnostic facilities and appropriate
treatment regimens are not available, and control
Tetracycline No prophylaxisb
3.0 (2/66) 46.6 (28/60)
93%
programmes should therefore focus on ocular pro-
phylaxis.
Proposed interventions
Cultural acceptability, political feasibility and
psychosocial effects
A major objection to the use ofsilver nitrate therapy has
been the high incidence ofchemical conjunctivitis. Some
developing countries even abandoned ocular prophyl-
axis because of this. The problem can be overcome by
using tetracycline ointment instead of silver nitrate
drops, which is at least as effective and has no side-
effects.
Instilling drops or ointment in the eyes of a new-
born may decrease visual alertness of the infant during
the first hours of life. These problems are of concern to
those who believe this may impair maternal-infant
bonding by reducing eye contact (S). However, any
potential impairment ofmaternal-infant bonding does
not outweigh the increased risk of GCON from
delaying the instillation of ocular prophylaxis.
Cost-effectiveness and feasibIlfty
The strategy of detection and treatment of gonococcal
infections in pregnancy has the advantage of not only
reducing GCON but also other maternal complications.
It is, however, a very expensive (if the goal is to reduce
GCON) and operationally complicated strategy, and
it is currently not feasible in most areas of the
developing countries.
The cost of the use of ocular prophylaxis has been
compared with the cost of early diagnosis and treat-
ment of GCON in a group of 1000 women, with
a prevalence of gonococcal infection of 10% (Table 6).
The cost for 1000 prophylactic regimens is US$100 for
silver nitrate 1 % drops (single-dose wax ampoules)
and $50 for tetracycline 1% ointment (multidose tubes
for 10 babies, $0.50 per tube). It is estimated that
despite ocular prophylaxis, 7% and 3% of the babies
in the silver nitrate and tetracycline group, respec-
475
M. Laga et al.

Table 6: Estimate of costs for the control of GCON among 1000 pregnant women with prevalences of gonococcal Infection of
10% and 1%
Silver nitrate Tetracycline No prophylaxis

Cost of 1 dose US$ 0.10 $0.05

(single-dose (multidose
ampoule) tubes)
Cost for 1000 neonates $100 $50
Attack rates of GCON among newborns' 7% 3% 47%
10% prevalence:
Cost of treatment of GCON (single dose, $5)b $35 $15 $235
Total cost $135 $65 $235
Cost per adverse outcome avertedc $2.90 $1.40 $5
1% prevalence:
Cost of treatment of GCON (single dose, $5)b $3.50 $1.50 $23.50
Total cost $103.50 $51.50 $23.50
Cost per adverse outcome avertedc $22 $11 $5
' Rates based on Nairobi clinical trial (17, 18); see Table 5.
bOptimal treatment for GCON is ceftriaxone 125 mg, IM single dose (16).
cAdverse outcome includes only GCON here.

tively, will develop GCON, compared to 47% of those
who receive no prophylaxis.
The price of one treatment regimen for GCON
varies from $5 (ceftriaxone 125 mg, intramuscular
single dose) to $2 (kanamycin 75 mg+ topical tetra-
cycline) (16). The assumption is that each case of
GCON would be brought to the health care facilities
and receive appropriate treatment.
The total cost of the three programmes (silver
nitrate, tetracycline, and no prophylaxis) for a group of
1000 women (with a 10% prevalence of GCON) is
$135, $65 and $235, respectively, resulting in a cost per
adverse outcome averted of $2.90, $1.40 and $5 (see
Table 6). Indirect costs of visual impairment due to late
or inadequate treatment are not taken into account.
It is clear that the strategy of ocular prophylaxis is
more cost-effective than early diagnosis and treatment.
It is furthermore more convincing on humanitarian
grounds, especially in areas where availability of
efficacious drugs are scarce.
In low-prevalence areas of maternal gonococcal
infection (<1%), the price of ocular prophylaxis is
higher than the price of treatment of actual cases with
GCON (see Table 6). However, the potential risk of
blindness (if not adequately treated) warrants further
use of ocular prophylaxis in all countries where the
coverage of health care is not optimal.
Resume
Epidemlologle et prevention de l'ophtalmle
du nouveau-ne
Les etiologies les plus importantes de l'ophtalmie
du nouveau-ne sont N. gonorrhoeae et C. trachomatis.
476
Du point de vue de la sante publique, l'ophtalmie
gonococcique (OGNN) est prioritaire puisque cette
affection peut mener rapidement a la cecite chez le
nouveau-ne. La frequence de l'OGNN depend de la
prevalence de l'infection gonococcique chez les femmes
enceintes. Dans la plupart des pays industrialises, cette
prevalence est inferieure a 1%. Dans les pays en
developpement, elle est souvent comprise entre 3% et
15%, et plus de la moitie des infections sont dues a des
souches de N. gonorrhoeae productrices des penicill-
inase (NGPP). Cela signifie que la penicilline n'est plus
efficace pour traiter l'OGNN et que si des antibioti-
ques efficaces, qui sont plus coiuteux, ne sont pas
disponibles, le risque de cecite est considerable pour le
nouveau-ne. Celui-ci est infecte a l'accouchement
pendant le passage dans la filiere genitale. Le taux de
transmission du gonocoque du col uterin aux yeux du
nouveau-ne est de 30 a 50%.
Les strategies de lutte contre l'OGNN sont: 1)
prevention de la gonococcie chez les femmes en age de
procreer, 2) depistage et traitement de la gonococcie
chez la femme enceinte, 3) prophylaxie oculaire chez le
nouveau-ne immediatement apr's la naissance, et 4)
diagnostic et traitement de l'OGNN.
La femme peut se proteger de la gonococcie et des
autres maladies sexuellement transmissibles (MST)
par un comportement sexuel adapte et l'utilisation du
preservatif par le partenaire.
Le depistage de la gonococcie chez la femme
enceinte suivi d'un traitement adequat previent aussi
bien les complications chez la femme que chez le
nouveau-ne (OGNN). Mais la prevalence de la gono-
coccie etant basse dans la plupart des pays industria-
lises, cette strategie a un rapport coiut/efficacite trop
faible. Un depistage selectif, c'est-a-dire dans des
sous-groupes de femmes enceintes a risque eleve de
 Epidemiology and control of gonococcal ophthalmia neonatorum
gonococcie, peut etre envisage. Dans les pays en
developpement, le facteur limitant pour le depistage
est le manque d'infrastructures de laboratoire. Le test
recommande est la culture du gonocoque, peu reali-
sable en dehors de quelques centres de reference dans
ces pays. Dans des conditions de haute prevalence de la
gonococcie chez la femme enceinte, un traitement
systematique pourrait eventuellement etre envisage.
L'instauration d'une prophylaxie oculaire imme-
diatement apres la naissance est tres efficace. Par
l'utilisation soit de collyre de nitrate d'argent a 1%,
soit de pommade ophtalmique de tetracycline a 1%,
l'incidence de l'OGNN diminue de 80 a 95% et cette
strategie a un rapport coutt/efficacite eleve, particuliere-
ment lorsque la prevalence de la gonococcie chez la
femme enceinte est elevee.
Le diagnostic et le traitement adequat comme
strategie principale de lutte contre l'OGNN ne sont
acceptables que dans les pays a faible prevalence de
gonococcie chez la femme enceinte et oiu la couverture
et la qualite des services de sante sont optimales. II est
donc clair que la prophylaxie oculaire reste la strategie
de choix dans tous les pays et regions otu la couverture
sanitaire laisse encore a desirer.
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