Part vi
The Conjunctiva
Section 2 Conjunctivitis
Chapter 40 
Conjunctivitis: An Overview and Classification
Thomas D. Lindquist, T. Peter Lindquist
Key Concepts
• The morphology, type of exudate, and principally
affected areas help define the etiology of conjunctivitis.
• Chronicity plays a key role in classifying conjunctivitis.
• Newly emerging viruses may cause conjunctivitis and
are important to recognize.
• Masquerade syndromes must be considered in cases
of chronic conjunctivitis.
The conjunctiva is a thin, translucent mucous membrane
whose palpebral portion lines the posterior surface of the
eyelids, and whose bulbar portion lines the anterior surface
of the globe. The conjunctiva is firmly adherent to the lids
over the tarsal plates and loosely attached in the fornices
and over the globe, with the exception of the limbus.
As with other mucous membranes, the conjunctiva has
an epithelial layer and a submucosal substantia propria. The
conjunctival epithelium is contiguous with the corneal epi-
thelium and also lines the lacrimal passages and glands, a
fact that has significant clinical implications. The substantia
propria is composed of a superficial adenoid layer and a
deeper fibrous layer. The adenoid layer contains lymphoid
tissue from which follicles are formed. Within the lymphoid
tissue are germinal centers with lymphoblasts in the more of the following: (1) the history and clinical examina-
center. The fibrous layer is composed of connective tissue, tion; (2) Gram and Giemsa stains of conjunctival scrapings;
which attaches to the tarsal plate and contributes to the
characteristic appearance of papillae.1
The formation of papillae is a nonspecific sign of conjunc-
tival inflammation resulting from edema and polymorpho-
nuclear (PMN) cell infiltration of the conjunctiva. Papillae
can form only where the conjunctiva is attached to the
underlying tissue by anchoring septae, such as over the
tarsus or the bulbar limbus. Fibroblasts, macrophages, mast
cells, and PMNs are found extravascularly within the sub-
stantia propria. Mast cells (5000 mm3) and plasma cells are
normally present in the substantia propria, but not in underlying etiology of conjunctivitis. Chronicity plays an
the conjunctival epithelium. Neutrophils and lymphocytes
(100 000 mm3) are routinely found in both conjunctival
epithelium and substantia propria, whereas basophils and
eosinophils are not normally present in either conjunctival
epithelium or substantia propria.2,3
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Conjunctival Injection
The conjunctival vessels are derived from the anterior ciliary
and palpebral arteries. Conjunctival injection is character-
ized by superficial bright red blood vessels, which are most
conspicuous in the fornices and fade toward the corneo-
scleral limbus. These vessels move as the conjunctiva is
mechanically manipulated and are blanched by topical
instillation of phenylephrine.
Conjunctival hyperemia is secondary to dilation of the
conjunctival blood vessels without accompanying exuda-
tion or cellular infiltration. Hyperemia may be caused by
a multiplicity of environmental factors including smoke,
smog or chemical fumes, wind, ultraviolet radiation, and
prolonged topical instillation of vasoconstrictors.
Conjunctivitis
Conjunctivitis implies inflammation of the conjunctiva and
is characterized by cellular infiltration and exudation in
addition to vascular dilation. Chemosis, an accumulation
of fluid within or beneath the conjunctiva, is frequently
present. The patient may complain of eyelid fullness and a
diffuse, gritty foreign body sensation. Frequently, patients
may notice a discharge that causes the eyelids to stick
together. The condition may be unilateral or bilateral.
The diagnosis of conjunctivitis may be based on one or
and (3) culture and identification of conjunctival scrapings.
Patient history can be helpful. Infectious disease is often
bilateral and may involve other members of the family or
community. Most cases of acute viral conjunctivitis initially
involve one eye, followed a few days later by involvement
of the other eye. The presence of an enlarged preauricular
lymph node suggests a viral etiology. Unilateral involvement
may suggest a toxic, pharmacological, mechanical, or lacri-
mal origin.
Several diagnostic criteria are helpful in determining the
important role and is the most widely used criterion for clas-
sification of conjunctivitis. An acute conjunctivitis is arbi-
trarily defined as having a duration of less than three weeks,
whereas chronic conjunctivitis has a longer duration of
symptoms.4,5 The morphologic appearance, type of exudate,
 CHAPTER 40
Conjunctivitis: An Overview and Classification

Chapter Outline
Conjunctival Injection
Conjunctivitis
Acute Conjunctivitis
Chronic Conjunctivitis

466.e1
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 CHAPTER 40
Conjunctivitis: An Overview and Classification

Hyperacute conjunctivitis Fig. 40.1  An algorithm for

Gram stain diagnosing acute conjunctivitis.
Purulent exudate N. gonorrhoeae
Bacterial cultures (Adapted from Buttross M,
N. meningitidis
Papillary Stern GA: Acute conjunctivitis.
Cultures Bacterial conjunctivitis In: Margo C, Hamed LM,
Catarrhal exudate
(Staph, Strep, Haemophilus) Mames RN, editors: Diagnostic
problems in clinical
Watery exudate Immunofluorescent tests ophthalmology. Philadelphia:
Viral conjunctivitis
Acute Tender node Serology WB Saunders; 1994. Copyright
Follicular
conjunctivitis Immunofluorescent tests Elsevier 1994.)
Catarrhal exudate Inclusion conjunctivitis
Chlamydial culture

Bacterial conjunctivitis
Positive bacterial culture
(Strep, Diphtheria)
Membranous
Negative bacterial culture Viral conjunctivitis

and principally affected areas of the conjunctiva are the

other most important physical findings that help define the Box 40.1 Follicular conjunctivitis
 

etiology of conjunctivitis.
In addition to the chronicity of conjunctivitis, five mor- I. Acute follicular conjunctivitis
phologic responses can be identified that help define algo- A. Adenovirus
rithms for acute or chronic conjunctivitities (Figs 40.1 and 1. Epidemic keratoconjunctivitis
2. Pharyngeal conjunctival fever
40.2): papillary, follicular, membranous/pseudomembranous,
3. Acute, nonspecific follicular conjunctivitis
cicatrizing, granulomatous. Proper identification of the mor- B. Inclusion conjunctivitis
phologic response is crucial to the correct diagnosis. C. Herpesviruses
1. Herpes simplex (primary)
Morphologic responses 2. Epstein−Barr virus
D. Paramyxoviruses (measles, mumps, Newcastle disease)
Papillae E. Poxviruses (smallpox, vaccinia and monkeypox)
F. Picornaviruses (acute hemorrhagic conjunctivitis)
Papillae are found only where the conjunctiva is attached to G. Orthomyxoviruses (influenza)
the underlying tissue by anchoring septae. The anchoring H. Togaviruses (rubella, yellow fever, dengue, and sandfly
septae normally divide the conjunctiva into a mosaic pattern fever)
of polygonal papillae, each less than 1 mm in diameter.6 II. Chronic follicular conjunctivitis
Papillae are characterized by folds or projections of hyper- A. Chlamydial infections
trophic epithelium that contain a central fibrovascular core 1. Trachoma
whose blood vessels arborize on reaching the surface (Fig. 2. Inclusion conjunctivitis
40.3). A papillary response is a nonspecific sign of conjunc- B. Molluscum contagiosum
tival inflammation resulting from edema and PMN cell infil- C. Moraxella
D. Parinaud oculoglandular syndrome
tration of the conjunctiva. Papillae in the tarsal conjunctiva
E. Lyme disease
tend to be flat-topped, whereas those at the limbus tend F. Toxic conjunctivitities
to be dome-shaped. When the upper tarsal conjunctiva is G. Folliculosis
everted, the superior edge may contain large papillae, which
may be a normal finding resulting from the paucity of
anchoring septae in this area.
Giant papillae may develop from breakdown of the fine,
fibrous strands that make up the anchoring septae. Giant
upper tarsal conjunctiva and the lower cul-de-sac; however,
papillae are greater than 1 mm in diameter and are most
they also can be seen at the limbus. Follicles are typically
commonly found in the upper tarsal conjunctiva. They can
0.5–2.0 mm in diameter, although follicles larger than 2 mm
be seen in vernal conjunctivitis, atopic keratoconjunctivitis,
in diameter are seen, particularly in chlamydial disease.1
and as a foreign body reaction to suture material, contact
Follicles are lymphoid germinal centers with fibroblasts in
lenses, or prostheses.
the center, and may be seen in the normal conjunctiva,
especially temporally in young patients. Folliculosis of child-
Follicles hood is not a disease entity but a physiologic change of
Follicles are yellowish-white, discrete, round elevations of childhood and adolescence in which follicles tend to be
conjunctiva produced by a lymphocytic response. Unlike a prominent in the fornix and fade out toward the lid margin.
papilla, the central portion of the follicle is avascular, with A follicular response is extremely important to identify
blood vessels sweeping up over the convexity from the because it is a relatively specific inflammatory response with
base (Fig. 40.4). Follicles are most readily appreciated in the a well-defined differential diagnosis (Box 40.1).

467
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 PART vi The Conjunctiva

Section 2 Conjunctivitis

Palpebral form
Vernal keratoconjunctivitis
Limbal form

Giant papillary Atopic keratoconjunctivitis

Contact lenses
Secondary giant papillary
Prostheses
conjunctivitis
Loose sutures
Chronic
dacryocystitis
Lacrimal infection
Unilateral Canaliculitis
Masquerade
syndrome Superior limbic
keratoconjunctivitis

Upper tarsal Floppy eyelid

conjunctiva principally syndrome

Foreign body
Papillary Variable
Toxic
Lower tarsal
conjunctiva principally Mucus-fishing
syndrome
Keratoconjunctivitis
sicca
Bilateral
Chronic Blepharoconjunctivitis
conjunctivitis Moraxella

Molluscum contagiosum

Follicular Lyme disease

Toxic
Inclusion conjunctivitis
Chlamydial infection
Trachoma
Membranous Ligneous conjunctivitis

Pemphigoid

Stevens-Johnson syndrome
Cicatrizing
Alkali burn

Trachoma

Parinaud's oculoglandular
syndrome
Granulomatous
Sarcoid

Fig. 40.2  An algorithm for diagnosing chronic conjunctivitis. (Adapted from Buttross M, Stern GA: Acute conjunctivitis. In: Margo C, Hamed LM,
Mames RN, editors: Diagnostic problems in clinical ophthalmology. Philadelphia: WB Saunders; 1994. Copyright Elsevier, 1994.)

Corynebacterium diphtheriae and β-hemolytic streptococci were

Membranes
Membranes are composed primarily of fibrin that has
attached to the epithelial conjunctival surface. True mem-
branes leave a raw surface and cause bleeding when peeled
off, which differentiates them from pseudomembranes. The
distinction between the two, however, really reflects the
degree of the inflammatory response, as true membranes
signify more intense conjunctival inflammation. Historically,
the principal causes of membranous/pseudomembranous
conjunctivitis;6 however, adenoviral conjunctivitis is now
the most common cause in Western countries (Fig. 40.5),
followed by primary herpes simplex virus conjunctivitis.1,4
Other causes include vernal conjunctivitis, inclusion con-
junctivitis, and Candida. Stevens−Johnson syndrome (SJS)
and toxic epidermal necrolysis (TEN) affect mucous mem-
branes and skin. Bilateral pseudomembranous conjunctivitis

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Fig. 40.3  Fine papillary conjunctivitis. Note the fibrovascular core in
which the blood vessels arborize on reaching the surface.
Fig. 40.4  Follicular conjunctivitis involving the lower palpebral
conjunctiva secondary to culture-proven chlamydial disease. Note the
large follicles with blood vessels sweeping up from the base over the
convexity.
is common in these conditions and may lead to severe con-
junctival scarring, loss of goblet cells, entropion, trichiasis,
and limbal stem cell failure.7
Cicatrizing changes
Injury to the conjunctival epithelium does not provoke scar
formation. Scar formation ensues only when there is destruc-
tion of stromal tissue. The early stages of cicatrization consist
of foreshortening of the conjunctival fornix and stellate or
linear, lacey, subepithelial fibrosis. Subconjunctival cicatriza-
tion and scarring may have long-standing complications,
including cicatricial entropion and trichiasis. If the process
continues, foreshortening of the conjunctival fornix worsens
and symblepharon develops (Fig. 40.6). End stages of chronic
cicatrizing disease as seen in mucous membrane pemphigoid
include obliteration of the conjunctival fornix, keratiniza-
tion of the epithelium, and fusion of the eyelids known as
ankyloblepharon.8
Membranous conjunctivitis is generally an acute condi-
tion, but may result in subepithelial fibrosis and limited
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CHAPTER 40
Conjunctivitis: An Overview and Classification
Fig. 40.5  Membranous conjunctivitis secondary to epidemic
keratoconjunctivitis. The pseudomembrane is composed of fibrin and
polymorphonuclear leukocytes obscuring much detail of the palpebral
conjunctiva. Petechial hemorrhages (1) can be seen.
Fig. 40.6  Cicatrizing conjunctivitis secondary to mucous membrane
pemphigoid. Note the fine, lacy subepithelial fibrosis (1), foreshortening
of the inferior fornix (2), and symblepharon formation (3).
symblepharon formation. Scarring after membranous con-
junctivitis shows no predilection for any portion of the
conjunctiva.
Scarring from atopic keratoconjunctivitis tends to be focal
and located in the centers of giant papillae. Diffuse shrink-
age of the lower fornix may be seen, but entropion and
trichiasis tend not to occur.
Scarring from trachoma is quite specific. The pathogno-
monic sign is the cicatricial remains of a limbal follicle
known as Herbert’s peripheral pit. A line of cicatricial sub-
epithelial fibrosis may be seen near the superior border of
the upper tarsus known as Arlt’s line.9,10 Arlt’s line may be
seen in other diseases, but is an important finding in
trachoma. The disease process in trachoma always involves
the upper lid more severely than the lower lid. Dermatitis
469
 PART vi The Conjunctiva
Section 2 Conjunctivitis
Fig. 40.7  Granulomatous conjunctivitis secondary to Parinaud
oculoglandular syndrome. Conjunctival granulomas always affect the
conjunctival stroma.
herpetiformis, epidermolysis bullosa, SJS and TEN, and exfo-
liative dermatitis also may result in conjunctival scarring.
Granulomas
Conjunctival granulomas always affect the stroma. A con-
junctival granuloma may be seen in sarcoidosis or from a
retained foreign body. Parinaud oculoglandular syndrome is
a unilateral granulomatous conjunctivitis (Fig. 40.7) with a
localized follicular response, often associated with a visibly
swollen preauricular or submandibular lymph node. Fever
and other systemic signs may be present. A variety of infec-
tious agents may cause this syndrome, including cat-scratch
disease, tularemia, sporotrichosis, tuberculosis, syphilis, lym-
phogranuloma venereum, and rickettsiosis.11 A biopsy may
be required to establish the diagnosis.
Type of exudate
Conjunctival exudates may be classified as: (1) purulent or
hyperacute; (2) mucopurulent or catarrhal; and (3) watery.1,4,6
Hyperacute conjunctivitis has a rapidly progressive course,
with grossly purulent discharge. When the discharge is irri-
gated from the eye, it tends to re-form in minutes. A muco-
purulent or catarrhal discharge consists of a mixture of
mucus and pus and is most commonly seen in bacterial
or chlamydial conjunctivitis. A mucopurulent discharge
adheres firmly to the lashes, causing the eyelids to stick
together. A copious, watery discharge is more typical of viral
conjunctivitis.
Anatomic localization
The most severely affected area of the conjunctiva can be
helpful in determining a differential diagnosis. Trachoma
affects the upper tarsus more severely than the lower tarsus.
Follicles also may be seen at the upper limbus in trachoma.
Other disorders involving the upper palpebral conjunctiva
predominantly include superior limbic keratoconjunctivitis
and the floppy eyelid syndrome.
Vernal keratoconjunctivitis (VKC) is a chronic, allergic
conjunctival inflammation with seasonal exacerbations, par-
ticularly in the spring and early summer. Giant papillae may
be seen on the upper pretarsal conjunctiva. In black patients,
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the papillae have predilection for the limbus. In atopic kera-
toconjunctivitis (AKC), giant papillary hypertrophy predom-
inates in the upper lid, but also can be seen in the lower lid.
In contrast to symptoms of VKC, symptoms of AKC may be
present throughout the year. The chronicity of AKC may
lead to corneal vascularization and scarring and, in some
cases, conjunctival cicatrization.
Giant papillae also may be seen secondarily on the upper
tarsus in contact lens wearers, patients wearing prostheses,
or from exposed suture material. Secondary giant papillae
may be difficult to differentiate from follicles, as they tend
to have rounder apices, are more spherical, and have pale
centers. In follicular conjunctivitis, however, both the upper
and lower palpebral conjunctivae are affected, whereas in
secondary giant papillary conjunctivitis, only the upper
palpebral conjunctiva is typically affected.
Conditions principally affecting the lower tarsal conjunc-
tiva include toxic papillary conjunctivitis and the “mucus-
fishing syndrome.” The follicular response in inclusion
conjunctivitis is more pronounced inferiorly than superiorly.
Acute Conjunctivitis
Acute papillary conjunctivitis
The morphologic response and type of exudate are the most
important considerations in acute conjunctivitis. Acute pap-
illary conjunctivitis is nearly always bacterial. Hyperacute
conjunctivitis is most likely caused by Neisseria gonorrhoeae
or N. meningitidis and is characterized by a rapidly progres-
sive course with grossly purulent discharge. Corneal ulcer-
ation with resultant scarring is the major cause of visual loss
and can lead to corneal perforation. With the exception of
neonatal conjunctivitis, gonococcal conjunctivitis is nearly
always associated with genital infection where transmission
occurs by autoinoculation from the patient’s dominant
hand.6 Gonococcal conjunctivitis is more common than
meningococcal conjunctivitis, but the two are clinically
indistinguishable. Systemic dissemination, including septi-
cemia, can occur with either organism. Gram stain of con-
junctival scrapings should be carefully examined for the
presence of intracellular Gram-negative diplococci. Specific
identification of the organism can be established by culture
and sugar fermentation tests. Antimicrobial susceptibility
studies are essential because of the emergence of resistant
strains of Neisseria to penicillin.
Treatment of hyperacute conjunctivitis includes frequent
saline lavage of the corneas, topical antibiotic, and paren-
teral antibiotics. Public health screening of sexual contacts
is mandatory when N. gonorrhoeae is identified. If N. menin-
gitidis is isolated, close contacts must be treated with
prophylactic antibiotics.
Acute papillary conjunctivitis with a catarrhal or muco-
purulent exudate characterizes the majority of cases of bacte-
rial conjunctivitis. One or both eyes may be involved, and
the onset is acute. Signs include papillary hypertrophy, con-
junctival injection, a mucopurulent discharge, and crusting
of the eyelashes. The cornea may be involved by a secondary
punctate epitheliopathy that may affect vision. Staphylococ-
cus aureus, Haemophilus influenzae, and streptococci are the

most frequently isolated organisms.2,12,13 Cytologic examina-
tion using Giemsa or Wright’s stain reveals a preponderance
of PMNs in bacterial conjunctival infections. A specific lar conjunctivitis may be seen in children or adults and is
diagnosis can be established only by performing conjuncti-
val cultures. Broad-spectrum topical antibiotic therapy, in
general, results in rapid resolution.
Acute follicular conjunctivitis
Acute follicular conjunctivitis has a well-defined differential
diagnosis that includes viral infections and the early phase
of chlamydial inclusion conjunctivitis. Papillae may be seen
in addition to follicles, since papillae simply represent a
nonspecific response of conjunctival tissue to any acute or
chronic inflammatory condition.
Adenovirus
Adenovirus is responsible for the majority of cases of acute
viral conjunctivitis. Adenoviral infection may present as epi-
demic keratoconjunctivitis (EKC), pharyngeal conjunctival
fever (PCF), or nonspecific follicular conjunctivitis. Epidemic
keratoconjunctivitis is a highly contagious infection princi-
pally caused by adenovirus serotypes 8 and 19.14 Transmis-
sion commonly occurs by direct contact. Clinical symptoms
are seen approximately eight days after exposure. Symptoms
of EKC include a sudden onset of an acute, watery discharge
associated with foreign body sensation, and mild photopho-
bia. The infection generally involves first one eye and the
second eye a few days later, which typically has a milder
course. Preauricular node enlargement and tenderness is
common and is more prominent on the side initially
involved. The distinguishing feature of EKC is the pattern of
corneal involvement.
A few days after the onset of conjunctivitis, diffuse punc-
tate epithelial erosions develop on the cornea. These coalesce
into larger, coarse, epithelial infiltrates 7 to 10 days after
onset. Approximately two weeks after onset, the coarse,
epithelial infiltrates are replaced by focal subepithelial Primary herpes simplex keratoconjunctivitis and Epstein−Barr
infiltrates, which are randomly distributed throughout the
central cornea. The subepithelial infiltrates grow in intensity
during the third to fourth week of infection and may number
from 1 to 50 or more. The subepithelial infiltrates indicate
a delayed hypersensitivity response and may significantly
decrease vision for months. Because subepithelial infiltrates
and EKC are immunologic phenomena, treatment with
topical corticosteroids is indicated.
Transmission of EKC may occur in eye clinics where the
virus may be spread by unwashed hands or improperly
cleaned instruments. Adenovirus serotype 8 is resistant margin will develop corneal epithelial manifestations,18,20
to 70% isopropyl alcohol.15 Adequate sterilization can be
achieved with 500 to 5000 parts per million (PPM) sodium
hypochlorite. Alternatively, disposable tonometer tips may
be used with any patient who has follicular conjunctivitis.
The Centers for Disease Control recommends that infected
healthcare personnel avoid direct patient contact up to 14
days after onset of epidemic keratoconjunctivitis.16
Pharyngoconjunctival fever is an acute illness character-
ized by follicular conjunctivitis, pharyngitis, and fever. This
syndrome is most commonly caused by adenovirus types A rising antibody titer also may provide confirmatory evi-
3 and 7. Submandibular lymph node enlargement is dence of primary herpes simplex infection.
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CHAPTER 40
Conjunctivitis: An Overview and Classification
frequently present. Membrane formation is unusual, and
corneal involvement is distinctly absent. Nonspecific follicu-
typically a mild disease without an associated keratitis. It
may be caused by many serotypes of adenovirus.
Inclusion conjunctivitis
Inclusion conjunctivitis caused by Chlamydia trachomatis is
an oculogenital disease that most commonly occurs in sexu-
ally active young adults.10,17,18 Unlike trachoma, inclusion
conjunctivitis is rarely transmitted through eye-to-eye
contact. The incubation period ranges from 2 to 19 days, but
an acute follicular conjunctivitis begins approximately five
days after exposure.7,17 Onset tends to be more insidious
than with viral infections. Inclusion conjunctivitis is gener-
ally a unilateral condition. Fully developed follicles do not
present until the second or third week of disease and become
considerably larger and more opalescent than follicles seen
in viral disease. Without treatment, the conjunctivitis may
persist for months. Yellowish-white subepithelial infiltrates
may be seen in the corneal periphery and can be confused
with the subepithelial infiltrates of adenovirus. Micropannus
may develop at the superior limbus of the cornea, and a
superficial punctate epithelial keratitis may be noted.
Conjunctival scrapings reveal a preponderance of PMNs
with lymphocytes and plasma cells. Basophilic intracyto-
plasmic inclusions may be seen in epithelial cells, although
this finding is more common in neonatal chlamydial con-
junctivitis than in adult inclusion conjunctivitis. Because
inclusion conjunctivitis is a manifestation of a systemic
disease, therapy should be systemic. Doxycycline, 100 mg
twice a day for 7 to 14 days, is recommended; however, a
single oral dose of 1 g azithromycin has provided adequate
treatment for genital chlamydial disease.19 In chronic cases,
therapy for several weeks to months may be required.
Ocular herpes infections
virus (EBV) may cause an acute follicular conjunctivitis.
Primary herpes simplex infection is frequently associated
with a vesicular lesion on the lid margin, which helps
establish the diagnosis. The disease typically occurs in chil-
dren and may include fever, upper respiratory symptoms,
and a vesicular stomatitis or dermatitis. The conjunctivitis
characteristically has a watery discharge with preauricular
lymphadenopathy. Small ecchymoses may be seen on the
conjunctiva. Within two weeks of onset, 50% of patients
with primary herpes simplex virus (HSV) involving the lid
which may range from fine, corneal vesicles to dendritic
ulceration. Unlike the prominent dendritic figures seen in
recurrent disease, fine microdendrites are more common and
may involve both the cornea and conjunctiva.
In patients with vesicles on the eyelid or dendritic corneal
lesions, the clinical diagnosis is rarely in question. In the
absence of these findings, however, conjunctival scrapings
can be obtained for fluorescent antibody testing or enzyme-
linked immunosorbent assay (ELISA), as well as for cultures.
471
 PART vi The Conjunctiva
Section 2 Conjunctivitis
Children with primary herpes ocular infections may have
such profuse tearing that topical trifluorothymidine may be
washed out rapidly. In such cases, the use of ganciclovir
ophthalmic gel 0.15% five times a day to the conjunctival
sac and eyelids may provide better delivery of antiviral
therapy. Neonates who develop herpes simplex primary con-
junctivitis also should receive intravenous treatment with
acyclovir.
EBV may cause a follicular or membranous conjunctivitis
with or without subconjunctival hemorrhage. The clinical
manifestations of primary EBV may range from silent bilateral has been reported in as many as 58% of infected
seroconversion to the classic syndrome of infectious mono-
nucleosis characterized by fever, sore throat, and lymphade-
nopathy. Serologic testing in patients with symptoms of
acute EBV infection manifests elevated IgM and IgG anti-
body levels against viral capsid antigen, and IgG response to
Epstein−Barr early antigen. Antibodies against Epstein−Barr
nuclear antigen do not develop until several weeks or months
after the onset of clinical disease. Discrete, granular subepi-
thelial infiltrates may be seen with overlying punctate epi-
thelial keratitis. The corneal disease from EBV may closely
mimic that seen in adenoviral keratitis.21
RNA-containing viruses
The Paramyxoviridae include measles, mumps, and Newcastle
disease, all of which are capable of eliciting a follicular con-
junctivitis.22 Measles infection of the eye may result in a
mucopurulent conjunctivitis, mild epithelial keratitis, and
occasionally the development of whitish Koplik’s spots on
the conjunctiva or semilunar fold. Newcastle disease is
unique because it is a unilateral follicular conjunctivitis with
preauricular adenopathy. It is limited almost exclusively to
contact with poultry but is self-limited and does not require
therapy.
The Picornaviridae cause an acute hemorrhagic conjuncti-
vitis associated with a follicular conjunctivitis, which ini-
tially affects one eye and rapidly spreads to the other. All
patients develop a hemorrhagic bulbar conjunctival reaction
that is more pronounced temporally and takes one to two
weeks to resolve. The causative agents include enterovirus
type 70 or coxsackievirus type A24. Preauricular adenopathy
may be seen in 60% of affected individuals.22
The Orthomyxoviridae include the influenza virus, which
may cause severe bronchopneumonia, particularly in elderly
people. A follicular conjunctivitis with a mucopurulent dis-
charge may be noted.22
The Togaviridae include the causative agent of rubella and
the chikungunya virus which is transmitted via the Aedes
mosquito. These viruses cause hyperemia of the conjunctiva,
lid swelling, photophobia, and lacrimation in association
with the development of conjunctival follicles.22,23
Anterior uveitis is the most common presentation of chi-
kungunya virus with pigmented keratic preciitates, photo-
phobia, and retro-orbital pain.23 Chikungunya virus antigens
have been detected in keratocytes and in fibroblasts of the iris
and ciliary body, suggesting direct ocular involvement.24 Chi-
kungunya virus was detected in one-third of corneal donors
not known to be infected in the context of an outbreak in
islands of the Indian Ocean, suggesting that transmission of
the disease could occur through corneal transplantation.24
472
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The Flaviviridae are a family of viruses that include yellow
fever, dengue, sandfly fever, and West Nile virus. The most
common eye finding in West Nile viral infection is chorio-
retinitis. Rarely an acute hemorrhagic conjunctivitis with
bilateral subconjunctival hemorrhages can guide clinicians
toward early diagnosis of West Nile virus while serologic
testing is pending.25
Ebola virus is the most important genus of Filoviridae and
is known to cause hemorrhagic fever and coagulopathy with
a high mortality rate. Conjunctival injection that is usually
patients along with subconjunctival hemorrhage and exces-
sive lacrimation.26 Ocular manifestations may aid in the
diagnosis.
Poxviruses
The Poxviridae include variola (smallpox), vaccinia (cowpox),
monkeypox, and molluscum contagiosum. The poxviruses
are dermatotrophic DNA viruses that cause lesions of the
eyelids, conjunctiva, and rarely the cornea.22 Ocular compli-
cations have been reported in 5–9% of patients with small-
pox.27 Variola has been eradicated because of the efforts of
the World Health Organization; however, concerns have
been raised about the use of smallpox as a biological weapon.
Vaccinia virus, used for mass smallpox inoculation,
may be associated with eyelid and conjunctival infection,
corneal ulceration, disciform keratitis, iritis, optic neuritis,
and blindness.28 About 10 to 20 patients per million small-
pox immunizations develop ocular complications, usually
through accidental autoinoculation with fingers or fomites
from the vaccination site to the eye.28
Monkeypox, like variola and vaccinia, is an orthopox
virus and was first isolated from a colony of sick monkeys.
The virus is acquired through contact with an animal’s
blood or through a bite. Secondary attack rates from person-
to-person are less than 10%, whereas for smallpox they are
70% with a mortality as high as 50%.29 Monkeypox appears
as a pustular rash affecting the head, trunk, and extremities.
The rash of monkeypox is exactly like that of smallpox,
although monkeypox is associated with more lymphade-
nopathy than is smallpox.29 Unlike varicella, where vesicular
lesions are characteristically in different stages of develop-
ment and healing, monkeypox lesions are all essentially at
the same stage.
Molluscum contagiosum may cause a chronic follicular
conjunctival reaction (see Chronic Conjunctivitis below).
Acute membranous conjunctivitis
Acute membranous or pseudomembranous conjunctivitis
develops as fibrin coagulates on the epithelial surface, which
may obscure the underlying morphologic response of the
conjunctiva, making further classification difficult. Acute
membranous conjunctivitis may be caused by both viral
and bacterial organisms. Adenoviral conjunctivitis caused by
EKC is now the most common cause, followed by HSV con-
junctivitis.22 β-hemolytic streptococci and S. aureus are the
most common bacterial causes for membranous conjunctivi-
tis. C. diphtheriae was previously the most common bacterial
cause,6 but is now rarely seen. Nevertheless, because of the
potential for bacteria to cause membranous conjunctivitis,

cultures need to be obtained when there is any question
about the etiology of the infection. Noninfectious causes
of membranous conjunctivitis, such as chemical injury,
Stevens−Johnson syndrome, or vernal conjunctivitis, are
readily distinguished, based on the history or associated
systemic findings.
Chronic Conjunctivitis
In chronic conjunctivitis, the conjunctival morphology and
anatomic localization are the most important variables.5
Unlike most causes of acute conjunctivitis, the diseases
causing chronic conjunctivitis are not usually self-limited.
In contrast to the majority of cases of acute conjunctivitis,
which are infectious in nature, the causes of chronic
conjunctivitis include immunologic, traumatic, toxic, Giant papillae are >1 mm in diameter by definition. Vernal
neoplastic, as well as infectious factors.
Clinical evaluation of a patient with chronic conjunctivi-
tis begins with a detailed history. The onset of chronic con-
junctivitis is usually insidious, and the progression of the
disease may be slow. Symptoms generally include ocular
discomfort, conjunctival injection, and perhaps a discharge.
Symptoms of severe pain or photophobia generally suggest
some corneal involvement. Many patients have used a
variety of medications to treat the disorder; therefore, a
careful medication history is essential. A history of animal
exposure, trauma, surgery, and foreign travel are all impor-
tant considerations.
The clinician should ask the patient to describe ocular
discomfort in some detail. Itching is the most prominent
feature of allergic disease. Irritation that is worse in the
morning may suggest blepharoconjunctivitis, whereas a
gritty sensation that worsens later in the day may suggest
keratoconjunctivitis sicca.
A thorough eye examination is important, but particular
attention should be paid to the skin and eyelids. The skin
should be examined for signs of atopic dermatitis, seborrheic
dermatitis, or rosacea. Preauricular and submandibular
nodes should be palpated for the presence of lymphade-
nopathy. The eyelids should be inspected for the loss of
eyelashes; the presence of tumors, papillomas, and mollus-
cum contagiosum lesions; and for signs of blepharitis. The
lacrimal drainage system should be evaluated for obstructive
disease or for signs of infection. The conjunctiva is examined
carefully for the presence of follicles or foreign bodies, and
the upper lid should be everted to examine the pretarsal
conjunctiva. The corneal examination should include the
use of fluorescein, lissamine green, or rose Bengal dyes, as
well as careful evaluation of any keratitis, vascularization,
peripheral scarring, or stromal inflammation. Morphologic
responses critical to establishing a correct diagnosis include
papillary, giant papillary, follicular, membranous, cicatriz-
ing, and granulomatous responses.
Laboratory investigation may be invaluable in some cases
of chronic conjunctivitis. Conjunctival scrapings can help
identify inflammatory and infectious microorganisms. The
presence of eosinophils is a reliable indicator of an allergic
disorder such as atopic or vernal keratoconjunctivitis. Unlike VKC, atopic keratoconjunctivitis (AKC) shows no
In chronic chlamydial infection, conjunctival scrapings
stained with Giemsa may reveal basophilic intracytoplasmic
inclusion bodies within epithelial cells. Immunofluorescent
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CHAPTER 40
Conjunctivitis: An Overview and Classification
studies may be confirmatory for chlamydial or herpes
simplex disease. Gram stain or culture of a scraping may
identify Moraxella, which is an unusual bacterial cause of
chronic follicular conjunctivitis. Cultures also can be crucial
in establishing a diagnosis of dacryocystitis or canaliculitis.
A conjunctival biopsy may reveal a neoplastic etiology,
identify a noncaseating or foreign body granuloma, or
uncover microorganisms. Immunofluorescence microscopy
of a conjunctival biopsy may confirm suspicion of mucous
membrane pemphigoid (ocular cicatricial pemphigoid) in
which immunoglobulin or complement may be seen bound
to the conjunctival basement membrane.
Giant papillary conjunctivitis
and atopic keratoconjunctivitis compose the two primary
forms of giant papillary conjunctivitis (GPC). Secondary
forms of GPC are related to contact lenses, ocular prostheses,
or exposed sutures. In allergic disorders, such as vernal kera-
toconjunctivitis, giant papillae may measure several milli-
meters in diameter and assume a flat top and polygonal
shape, giving rise to the description of “cobblestone” papil-
lae. Secondary forms of giant papillae assume a rounder
shape with pale centers. Although these secondary giant
papillae may be confused with follicles, the lower fornix is
never involved in secondary GPC.
Vernal keratoconjunctivitis
Vernal keratoconjunctivitis (VKC) is a seasonally recurrent,
bilateral conjunctival inflammation of youth; boys are
affected twice as often as girls. The most prominent symptom
is itching, which can become worse toward evening and is
exacerbated by rubbing. Tearing is characteristic and macer-
ates the skin about the corner of the eye. A characteristic
thick, mucoid, ropy discharge is noted.30
Clinically, VKC may be divided into a palpebral and
limbal form. These two forms may occur together, although
the limbal form is more common in blacks. Palpebral VKC
is characterized by the formation of giant papillae on the
upper pretarsal conjunctiva. The conjunctiva of the lower
eyelid shows a diffuse, fine papillary reaction. In limbal VKC,
both the upper and lower papillary conjunctiva reveal a fine,
diffuse papillary reaction. The limbal form is marked by
thickened, broad, gelatinous opacification of the upper
limbus. Within the thickened areas are whitish chalklike
excrescences called Trantas dots, which are concretions of
eosinophils that may be evanescent. Corneal involvement
may range from a punctate epithelial keratitis to a “vernal
ulcer,” which is a sterile shield-shaped epithelial defect at
the junction of the upper and middle third of the cornea.
The diagnosis of VKC may be made by examination of
conjunctival scrapings of the upper tarsus. Greater than two
eosinophils per high-power field is diagnostic of VKC.
Atopic keratoconjunctivitis
seasonal variation. Onset is generally during the late teens;
in most cases AKC improves or “burns out” by the fourth or
fifth decade.
473
 PART vi The Conjunctiva
Section 2 Conjunctivitis
The lid margins may be indurated and lichenified. Giant
papillary hypertrophy is noted in the upper and lower lids.
Corneal scarring and foreshortening of the conjunctival
fornix may occur secondary to the chronicity of the disorder.
Conjunctival scrapings reveal mast cells, basophils, eosino-
phils, and possible lymphocytes.30
Secondary giant papillary conjunctivitis
Secondary giant papillary conjunctivitis occurs most com-
monly in soft contact lens wearers.30 Patients complain of a
foreign body sensation and ocular discomfort. Mucinous
and proteinaceous deposits are frequently present on the
contact lenses. Similar complaints and findings may be
noted in patients with ocular prostheses or loose or broken
sutures.
Chronic papillary conjunctivitis
Chronic papillary conjunctivitis has several different etiolo-
gies. Anatomic localization and the differentiation of unilat-
eral or bilateral involvement can be helpful in establishing
a correct diagnosis.5
Masquerade syndrome
A chronic, unilateral papillary conjunctivitis should arouse
the suspicion of a masquerade syndrome caused by an
underlying ocular surface malignancy. Chronic conjunctival
inflammation may be associated with intraepithelial neopla-
sia, pigmented or amelanotic melanoma, and sebaceous cell
carcinoma.
Intraepithelial neoplasia
Squamous dysplasia or intraepithelial neoplasia of the con-
junctiva nearly always arises at the limbus and, more com-
monly, in the intrapalpebral area. The lesions appear as
raised, somewhat gelatinous masses, which may be gray or
slightly red.31 The extent of the lesion is best visualized by
application of rose Bengal dye. Treatment involves conjunc-
tival excision and scraping of the epithelial extension onto
the cornea. The limbus, base, and conjunctival margin are
frozen with a retinal cryoprobe in a rapid, double freeze-
thaw manner.32
Malignant melanoma
Malignant melanoma can arise in clear conjunctiva in 10%
of cases, from a pre-existing nevus in 20–30% of cases, or
from primary acquired melanosis in 60–70% of cases.33,34 It
is particularly rare before the third decade of life. Clinically,
lesions can be pigmented or nonpigmented, are elevated,
and can affect any portion of the conjunctiva.34 Treatment
is by wide local excision followed by freeze–thaw–freeze
cryotherapy.34 Topical interferon-alfa has been shown to
cause regression of conjunctival and corneal melanoma.35
Topical mitomycin C may be used as an adjuvant therapy
for conjunctival melanoma.36
Sebaceous cell carcinoma
Sebaceous cell carcinoma arises from meibomian glands
most commonly, although it can also develop in Zeis’ glands
474
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or from sebaceous glands in the caruncle. Patients with an
unexplained unilateral conjunctivitis should undergo biopsy
that includes the tarsus and conjunctiva or skin. Sebaceous
cell carcinoma often spreads in a pagetoid fashion within
the epithelium, requiring multiple conjunctival biopsies.
Clues to the correct diagnosis include eyelid thickening
and deformity, focal loss of eyelashes, unilateral involve-
ment, and an abnormal papillary conjunctival inflamma-
tion. A full-thickness wedge biopsy should be performed to
definitively diagnose this disorder. Sebaceous cell carcinoma
is a life-threatening disorder, and early diagnosis may be
lifesaving.37
Lacrimal drainage system infection
Chronic dacryocystitis
Chronic dacryocystitis or chronic canaliculitis may lead to
a chronic papillary conjunctivitis secondary to infectious
organisms. Chronic dacryocystitis occurs in the presence of
lacrimal outflow obstruction distal to the lacrimal sac.38 This
obstruction causes stasis of tears within the lacrimal sac,
which leads to secondary bacterial colonization and infec-
tion. An acute lacrimal sac abscess may develop; however, if
the common canaliculus remains patent, a chronic conjunc-
tivitis may develop as purulent material drains in a retro-
grade fashion. Patients may initially complain of epiphora
before the onset of chronic conjunctival irritation and a
mucopurulent discharge. Examination typically reveals a
unilateral, diffuse papillary conjunctivitis with a mucopuru-
lent discharge. When pressure is applied over the lacrimal
sac, reflux of purulent material can be observed through the
punctum and is diagnostic of dacryocystitis. The skin overly-
ing the lacrimal sac may be quite tender and swollen. Con-
junctival cultures are necessary to identify the infectious
etiology. Staphylococci and streptococci are the most
common organisms isolated; however, a wide variety of bac-
terial and fungal organisms have been noted. Treatment
involves oral and topical antibiotics. Once the infection
is resolved, obstruction distal to the lacrimal sac needs to
be further investigated and patency established to avoid
recurrence.
Chronic canaliculitis
Chronic canaliculitis is frequently due to a diverticulum of
the canaliculus in which organisms proliferate. Symptoms
are similar to that of chronic dacryocystitis, except that
epiphora is absent.38 Examination reveals a papillary con-
junctivitis with mucopurulent discharge. Frequently, there
is a discharge from the punctal orifice. The punctum is often
enlarged and pouts externally. Mechanical expression of
infected material from the canaliculus is accomplished by
applying pressure using cotton-tipped applicators to both
the inner and outer surfaces of the medial aspect of the
eyelid while rolling the applicators toward the punctum.
Cheesy concretions may be expressed from the punctum.
The expressed material should be cultured for aerobic and
anaerobic bacteria and fungi. Gram stain of the exudate
often reveals a filamentous, branching, Gram-positive bac-
terium, which may be identified as Actinomyces israelii, the
most common cause of canaliculitis.39

The differential diagnosis of chronic papillary conjuncti-
vitis involving both eyes includes keratoconjunctivitis sicca,
blepharoconjunctivitis, and disorders that specifically have
a predilection for the upper palpebral conjunctiva, including
superior limbic keratoconjunctivitis, the floppy eyelid syn-
drome, and a retained foreign body.
Superior limbic keratoconjunctivitis
Superior limbic keratoconjunctivitis is a noninfectious
inflammatory disease characterized by: (1) velvety papillary
hypertrophy of the upper palpebral conjunctiva; (2) hyper-
emia and rose Bengal staining of the upper bulbar conjunc-
tiva; (3) micropannus and punctate rose Bengal staining of
the superior limbus; (4) thickening and keratinization of the
superior limbal, bulbar, and palpebral conjunctiva; and (5)
superior filamentary keratitis in about 50% of patients.40,41
Scrapings of the superior bulbar conjunctiva reveal keratin-
ized epithelial cells.
Floppy eyelid syndrome
The floppy eyelid syndrome is a distinct entity seen more
commonly in obese people and in those who sleep on their
stomachs. It is characterized by a rubbery, redundant upper
tarsus, which everts with minimal pressure. A chronic papil-
lary conjunctivitis is seen over the upper palpebral conjunc-
tiva and may be associated with corneal changes ranging
from mild punctate keratitis to superficial pannus.42 During
sleep, the upper eyelid is thought to evert, resulting in
mechanical contact with the pillow or other bed clothes
accounting for the chronic irritation. Treatment consists conjunctival staining with rose Bengal, most prominent
of a protective metal shield or taping the eyelids while
asleep. Surgical treatment is directed toward eyelid-tightening
procedures.
Blepharoconjunctivitis
Bilateral chronic papillary conjunctivitis is most frequently
caused by blepharoconjunctivitis or keratoconjunctivitis
sicca, which often coexist. Patients with blepharitis com-
plain of chronic burning, irritation, and foreign body sensa-
tion associated with photophobia if the cornea is involved.
Symptoms are frequently worse early in the morning. Bleph-
aritis may be classified as (1) staphylococcal/Demodex,
(2) seborrheic, and (3) meibomian, although patients with
blepharitis frequently exhibit signs from more than one
category.43
Staphylococcal/Demodex and seborrheic
Staphylococcal, Demodex and seborrheic forms are frequently
categorized as “anterior blepharitis,” whereas meibomian
gland dysfunction is characterized as “posterior blepharitis.”
Staphylococcal blepharitis is characterized by ulcerations
surrounding the lash follicle, which become crusted. As the
crusts are exfoliated, they surround the eyelash like a collar
from which the term collarette is derived. Demodex is a
microscopic mite that is the most common permanent ecto-
parasite of humans.44 Demodex infestation has been highly
correlated with cylindrical dandruff on the lashes and is
thought to be a cause of anterior blepharitis and allergic
conjunctivitis.45 Seborrheic blepharitis is probably the most
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CHAPTER 40
Conjunctivitis: An Overview and Classification
common cause of chronic lid inflammation and is part of a
generalized sebaceous gland abnormality in which hard, oily
scales may be seen clinging to the eyelashes.
Meibomian gland dysfunction
Meibomian gland dysfunction is characterized by thickening
of the eyelid margin, inspissated and thickened secretions of
the glands, dilation of the ducts of the glands, a foamy secre-
tion on the lid margins, and recurrent chalazia. Not uncom-
monly, meibomian gland dysfunction is associated with
ocular rosacea. Secondary colonization of meibomian glands
by staphylococcal organisms may further destabilize the tear
film. Treatment of blepharoconjunctivitis includes mechani-
cal cleansing of the eyelids, application of warm compresses,
systemic tetracyclines, oral supplementation of essential
fatty acids, and use of erythromycin or bacitracin antibiotic
ointment.
Keratoconjunctivitis sicca
The other principal cause of chronic, bilateral papillary con-
junctivitis is keratoconjunctivitis sicca. This disorder occurs
when the quantity or quality of the precorneal tear film
is insufficient to ensure the well-being of the ocular epithe-
lial surface.46 Symptoms include ocular discomfort, foreign
body sensation, and burning, all of which are worsened
by wind, smoke, low humidity, and environmental pollut-
ants. Symptoms tend to become worse as the day progresses.
Clinical signs of keratoconjunctivitis sicca include a decreased
tear lake, mucous debris in the tear film, and corneal and
in the interpalpebral fissure. Schirmer testing may be per-
formed with or without topical anesthesia. Wetting <5 mm
when performed without anesthesia is highly specific for
the diagnosis of keratoconjunctivitis sicca.47 Treatment is
directed toward artificial tear substitutes, anti-inflammatory
agents including short-term topical steroids and topical
cyclosporine, damming of the lacrimal outflow system, and
in severe cases, reducing the rate of evaporation through
tarsorrhaphy.
Mucus-fishing syndrome
A mechanically induced, chronic papillary conjunctivitis
has been described in patients with various underlying,
external ocular diseases, including keratoconjunctivitis sicca,
blepharitis, and allergic conjunctivitis. These patients exac-
erbate their conjunctival irritation by the frequent mechani-
cal removal of excess mucus from the surface of the globe
or from the inferior fornix. The entity has been called the
“mucus-fishing” syndrome and exacerbates the findings in
external ocular diseases in which the treatment might
otherwise be appropriate.48
Toxic papillary keratoconjunctivitis
Toxic papillary keratoconjunctivitis is the most common of
all adverse reactions to topical medications.49 The toxic
effects usually take at least two weeks to develop. Punctate
staining, best identified with rose Bengal dye, is more pro-
nounced on the inferonasal conjunctiva and cornea where
medications gravitate on their way to the lacrimal outflow
475
 PART vi The Conjunctiva
Section 2 Conjunctivitis
Box 40.2 Principal causes of toxic papillary reactions
Aminoglycoside antibiotics
  Neomycin
  Gentamicin
  Tobramycin
Nearly all “concentrated” or “fortified” antibiotics and antifungal
agents
Antiviral agents
  Idoxuridine
 Vidarabine
  Trifluorothymidine
Topical anesthetic agents
  Proparacaine
  Tetracaine
Preservatives
  Benzalkonium chloride
system. Hyperemia, nonspecific papillary conjunctivitis, and
scant mucoid discharge are noted clinically. Itching is absent,
and eosinophils are not seen in conjunctival scrapings. The
principal causes of toxic papillary reactions are aminoglyco-
side antibiotics, antiviral agents, and the preservative ben-
zalkonium chloride (Box 40.2). Benzalkonium is a particularly
frequent offender, not only because of its frequent use as a
preservative but also because it is a surfactant with detergent-
like properties.9
Factors predisposing to toxic papillary reactions include
keratoconjunctivitis sicca and other ocular surface dis-
orders, the prolonged use of medications, and the use of
multiple preparations. The mainstay of treatment is with-
drawal of offending medications and preservatives, the
use of preservative-free artificial tears, and substitution
with nonpreserved medications that can be formulated by
pharmacists.
Chronic follicular conjunctivitis
Chlamydia
Chlamydia trachomatis is the etiologic agent most frequently
responsible for chronic follicular conjunctivitis.5,10 Chla-
mydial disease may manifest as trachoma or inclusion
conjunctivitis.
Trachoma
Trachoma is endemic in most developing countries of the
world, and is the most common cause of blindness.17,18 In
endemic areas, children are affected within the first two
years of life and frequent reinfection associated with bacte-
rial superinfection prolongs the course of the disease.9,10,17,18
Active inflammation decreases with age, but the cicatricial
changes result in progressive lid deformity and corneal
changes for many years. Trachoma is a bilateral, chronic,
follicular conjunctivitis that causes conjunctival and corneal
scarring.9 During the infectious stage of the disease, large
follicles are seen most prominently in the upper fornix and
pretarsal conjunctiva. Limbal follicles also may be seen, and
as they eventually necrose and heal, shallow depressions
476
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described as Herbert’s peripheral pits are left. Limbal involve-
ment also results in a superficial vascular pannus, which is
most prominent superiorly.
Inclusion conjunctivitis
Inclusion conjunctivitis, which is often unilateral, is charac-
terized by follicles that are more pronounced in the inferior
conjunctival fornix. Fully developed follicles do not present
until the second or third week of the disease and may persist
for many months when untreated. The disease is generally
regarded as benign and self-limited in adults but can persist
for six months or longer.5,7,10
Moraxella
Moraxella organisms are large, Gram-negative diplobacilli
that can cause either a chronic follicular conjunctivitis or an
angular blepharoconjunctivitis. The latter is characterized by
ulceration of the lateral lid margin associated with conjunc-
tival injection. Proteases, produced by the Moraxella bacte-
rium, are thought to be responsible for the conjunctival
follicular responses.1
Molluscum contagiosum
Molluscum contagiosum is one of the DNA poxviruses that
may cause a chronic, follicular conjunctivitis. It is more
common in children and young adults, but can affect all age
groups. The typical lesions of molluscum contagiosum are
pink, umbilicated, seen on the eyelid margin of periocular
skin, and measure 2–3 mm in diameter. These lesions secrete
large quantities of virus, which spill onto the cornea or the
lower conjunctival fornix. Clinically, this is seen as a chronic
follicular conjunctivitis that may involve both the upper
and lower fornix and is associated with superficial punctate
keratitis and corneal pannus. These responses are most likely
a toxic reaction to the viral particles. The disease is spread
by close personal contact and may be transmitted sexually.
Treatment involves simple excision, curetting, or cryother-
apy of the lesions.
Toxic follicular conjunctivitis
Toxic follicular conjunctivitis may result from chronic
exposure to topical medications, eye make-up, and various
environmental pollutants. Follicles develop slowly, usually
requiring at least several weeks to develop.49 The mechanism
by which toxic follicular conjunctivitis develops is not
thought to be allergic, but most likely results from the ability
of certain drugs to act as nonantigenic mitogens that induce
mitotic and lymphoblastic transformations of lymphocytes
by nonimmunologic means.49 Nevertheless, true lymphoid
follicles with germinal centers containing lymphoblasts are
present. The follicles are most prominent in the lower fornix
and inferior palpebral conjunctiva. Hyperemia and punctate
staining are usually mild, if present. Principal causes of toxic
follicular conjunctivitis are shown in Box 40.3.49–52
Lyme disease
Lyme disease is the most common tick-transmitted illness
in the US. Ocular manifestations include blepharitis,

Box 40.3 Principal causes of drug-induced toxic
 
follicular conjunctivitis
Antiviral agents   Dipivefrin epinephrine
  Idoxuridine   Carbachol
 Vidarabine   Apraclonidine
  Trifluorothymidine   Brimonidine tartrate
Antiglaucoma agents Cycloplegic agents
  Pilocarpine   Atropine
  Echothiophate   Homatropine
  Epinephrine
conjunctivitis, keratitis, iritis, choroiditis, macular and disk
edema, and pseudotumor cerebri syndrome. The conjuncti-
vitis has now been described as follicular in nature and is
bilateral.53,54 Lyme disease is caused by the spirochete Borrelia
burgdorferi. The transient conjunctivitis is seen in early stages
of this disease. However, bilateral follicular conjunctivitis,
eyelid swelling, and regional lymphadenopathy may be the
only manifestation of Lyme disease if the tick bite is located
in the periorbital region.54 Therefore, inclusion of Lyme
disease as a cause of a chronic follicular conjunctivitis may
help establish an early diagnosis.
Chronic membranous conjunctivitis
The only chronic membranous conjunctivitis is ligneous
conjunctivitis.5 This rare, chronic conjunctivitis of unknown
origin occurs predominantly in young girls. Persistent
whitish membranes 1–2 mm thick form on the upper and
less frequently on the lower tarsal conjunctiva. Systemic
illnesses including fever, urinary tract, or upper respiratory
tract infections may precede the onset of ocular involvement.
The disease begins as a subacute inflammation of the tarsal
conjunctiva. An initial, subacute, membranous conjunctivi-
tis is followed by the development of sessile or pedunculated
masses of the tarsal conjunctiva.55,56 Infrequently, the bulbar
conjunctiva and cornea may be involved. These membranes
or masses may recur rapidly when excised.
Cicatrizing and granulomatous conjunctivitis
Cicatrizing and granulomatous conjunctivities are addi-
tional types of chronic inflammation and have been dis-
cussed in detail earlier in this chapter under morphologic
responses. Establishing the correct diagnosis of conjunctivi-
tis requires a deliberate history and a careful ocular and
adnexal examination. Particular attention to chronicity,
conjunctival morphology, anatomic distribution, and uni-
lateral versus bilateral involvement can help establish a
working differential diagnosis. Specific laboratory findings
may further identify the etiologic diagnosis.
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CHAPTER 40
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Section 2 Conjunctivitis

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