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The Conjunctiva
Section 2 Conjunctivitis
Chapter 40
Conjunctivitis: An Overview and Classification
Thomas D. Lindquist, T. Peter Lindquist
466
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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
Bacterial conjunctivitis
Positive bacterial culture
(Strep, Diphtheria)
Membranous
Negative bacterial culture Viral 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
Foreign body
Papillary Variable
Toxic
Lower tarsal
conjunctiva principally Mucus-fishing
syndrome
Keratoconjunctivitis
sicca
Bilateral
Chronic Blepharoconjunctivitis
conjunctivitis Moraxella
Molluscum contagiosum
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.)
468
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CHAPTER 40
Conjunctivitis: An Overview and Classification
469
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PART vi The Conjunctiva
Section 2 Conjunctivitis
Granulomas
Acute Conjunctivitis
Conjunctival granulomas always affect the stroma. A con-
junctival granuloma may be seen in sarcoidosis or from a Acute papillary conjunctivitis
retained foreign body. Parinaud oculoglandular syndrome is
a unilateral granulomatous conjunctivitis (Fig. 40.7) with a The morphologic response and type of exudate are the most
localized follicular response, often associated with a visibly important considerations in acute conjunctivitis. Acute pap-
swollen preauricular or submandibular lymph node. Fever illary conjunctivitis is nearly always bacterial. Hyperacute
and other systemic signs may be present. A variety of infec- conjunctivitis is most likely caused by Neisseria gonorrhoeae
tious agents may cause this syndrome, including cat-scratch or N. meningitidis and is characterized by a rapidly progres-
disease, tularemia, sporotrichosis, tuberculosis, syphilis, lym- sive course with grossly purulent discharge. Corneal ulcer-
phogranuloma venereum, and rickettsiosis.11 A biopsy may ation with resultant scarring is the major cause of visual loss
be required to establish the diagnosis. and can lead to corneal perforation. With the exception of
neonatal conjunctivitis, gonococcal conjunctivitis is nearly
Type of exudate always associated with genital infection where transmission
occurs by autoinoculation from the patient’s dominant
Conjunctival exudates may be classified as: (1) purulent or
hand.6 Gonococcal conjunctivitis is more common than
hyperacute; (2) mucopurulent or catarrhal; and (3) watery.1,4,6
meningococcal conjunctivitis, but the two are clinically
Hyperacute conjunctivitis has a rapidly progressive course,
indistinguishable. Systemic dissemination, including septi-
with grossly purulent discharge. When the discharge is irri-
cemia, can occur with either organism. Gram stain of con-
gated from the eye, it tends to re-form in minutes. A muco-
junctival scrapings should be carefully examined for the
purulent or catarrhal discharge consists of a mixture of
presence of intracellular Gram-negative diplococci. Specific
mucus and pus and is most commonly seen in bacterial
identification of the organism can be established by culture
or chlamydial conjunctivitis. A mucopurulent discharge
and sugar fermentation tests. Antimicrobial susceptibility
adheres firmly to the lashes, causing the eyelids to stick
studies are essential because of the emergence of resistant
together. A copious, watery discharge is more typical of viral
strains of Neisseria to penicillin.
conjunctivitis.
Treatment of hyperacute conjunctivitis includes frequent
saline lavage of the corneas, topical antibiotic, and paren-
Anatomic localization teral antibiotics. Public health screening of sexual contacts
The most severely affected area of the conjunctiva can be is mandatory when N. gonorrhoeae is identified. If N. menin-
helpful in determining a differential diagnosis. Trachoma gitidis is isolated, close contacts must be treated with
affects the upper tarsus more severely than the lower tarsus. prophylactic antibiotics.
Follicles also may be seen at the upper limbus in trachoma. Acute papillary conjunctivitis with a catarrhal or muco-
Other disorders involving the upper palpebral conjunctiva purulent exudate characterizes the majority of cases of bacte-
predominantly include superior limbic keratoconjunctivitis rial conjunctivitis. One or both eyes may be involved, and
and the floppy eyelid syndrome. the onset is acute. Signs include papillary hypertrophy, con-
Vernal keratoconjunctivitis (VKC) is a chronic, allergic junctival injection, a mucopurulent discharge, and crusting
conjunctival inflammation with seasonal exacerbations, par- of the eyelashes. The cornea may be involved by a secondary
ticularly in the spring and early summer. Giant papillae may punctate epitheliopathy that may affect vision. Staphylococ-
be seen on the upper pretarsal conjunctiva. In black patients, cus aureus, Haemophilus influenzae, and streptococci are the
470
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CHAPTER 40
Conjunctivitis: An Overview and Classification
most frequently isolated organisms.2,12,13 Cytologic examina- frequently present. Membrane formation is unusual, and
tion using Giemsa or Wright’s stain reveals a preponderance corneal involvement is distinctly absent. Nonspecific follicu-
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- typically a mild disease without an associated keratitis. It
val cultures. Broad-spectrum topical antibiotic therapy, in may be caused by many serotypes of adenovirus.
general, results in rapid resolution.
Inclusion conjunctivitis
Acute follicular conjunctivitis Inclusion conjunctivitis caused by Chlamydia trachomatis is
an oculogenital disease that most commonly occurs in sexu-
Acute follicular conjunctivitis has a well-defined differential ally active young adults.10,17,18 Unlike trachoma, inclusion
diagnosis that includes viral infections and the early phase conjunctivitis is rarely transmitted through eye-to-eye
of chlamydial inclusion conjunctivitis. Papillae may be seen contact. The incubation period ranges from 2 to 19 days, but
in addition to follicles, since papillae simply represent a an acute follicular conjunctivitis begins approximately five
nonspecific response of conjunctival tissue to any acute or days after exposure.7,17 Onset tends to be more insidious
chronic inflammatory condition. than with viral infections. Inclusion conjunctivitis is gener-
ally a unilateral condition. Fully developed follicles do not
Adenovirus present until the second or third week of disease and become
considerably larger and more opalescent than follicles seen
Adenovirus is responsible for the majority of cases of acute
in viral disease. Without treatment, the conjunctivitis may
viral conjunctivitis. Adenoviral infection may present as epi-
persist for months. Yellowish-white subepithelial infiltrates
demic keratoconjunctivitis (EKC), pharyngeal conjunctival
may be seen in the corneal periphery and can be confused
fever (PCF), or nonspecific follicular conjunctivitis. Epidemic
with the subepithelial infiltrates of adenovirus. Micropannus
keratoconjunctivitis is a highly contagious infection princi-
may develop at the superior limbus of the cornea, and a
pally caused by adenovirus serotypes 8 and 19.14 Transmis-
superficial punctate epithelial keratitis may be noted.
sion commonly occurs by direct contact. Clinical symptoms
Conjunctival scrapings reveal a preponderance of PMNs
are seen approximately eight days after exposure. Symptoms
with lymphocytes and plasma cells. Basophilic intracyto-
of EKC include a sudden onset of an acute, watery discharge
plasmic inclusions may be seen in epithelial cells, although
associated with foreign body sensation, and mild photopho-
this finding is more common in neonatal chlamydial con-
bia. The infection generally involves first one eye and the
junctivitis than in adult inclusion conjunctivitis. Because
second eye a few days later, which typically has a milder
inclusion conjunctivitis is a manifestation of a systemic
course. Preauricular node enlargement and tenderness is
disease, therapy should be systemic. Doxycycline, 100 mg
common and is more prominent on the side initially
twice a day for 7 to 14 days, is recommended; however, a
involved. The distinguishing feature of EKC is the pattern of
single oral dose of 1 g azithromycin has provided adequate
corneal involvement.
treatment for genital chlamydial disease.19 In chronic cases,
A few days after the onset of conjunctivitis, diffuse punc-
therapy for several weeks to months may be required.
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,
Ocular herpes infections
epithelial infiltrates are replaced by focal subepithelial Primary herpes simplex keratoconjunctivitis and Epstein−Barr
infiltrates, which are randomly distributed throughout the virus (EBV) may cause an acute follicular conjunctivitis.
central cornea. The subepithelial infiltrates grow in intensity Primary herpes simplex infection is frequently associated
during the third to fourth week of infection and may number with a vesicular lesion on the lid margin, which helps
from 1 to 50 or more. The subepithelial infiltrates indicate establish the diagnosis. The disease typically occurs in chil-
a delayed hypersensitivity response and may significantly dren and may include fever, upper respiratory symptoms,
decrease vision for months. Because subepithelial infiltrates and a vesicular stomatitis or dermatitis. The conjunctivitis
and EKC are immunologic phenomena, treatment with characteristically has a watery discharge with preauricular
topical corticosteroids is indicated. lymphadenopathy. Small ecchymoses may be seen on the
Transmission of EKC may occur in eye clinics where the conjunctiva. Within two weeks of onset, 50% of patients
virus may be spread by unwashed hands or improperly with primary herpes simplex virus (HSV) involving the lid
cleaned instruments. Adenovirus serotype 8 is resistant margin will develop corneal epithelial manifestations,18,20
to 70% isopropyl alcohol.15 Adequate sterilization can be which may range from fine, corneal vesicles to dendritic
achieved with 500 to 5000 parts per million (PPM) sodium ulceration. Unlike the prominent dendritic figures seen in
hypochlorite. Alternatively, disposable tonometer tips may recurrent disease, fine microdendrites are more common and
be used with any patient who has follicular conjunctivitis. may involve both the cornea and conjunctiva.
The Centers for Disease Control recommends that infected In patients with vesicles on the eyelid or dendritic corneal
healthcare personnel avoid direct patient contact up to 14 lesions, the clinical diagnosis is rarely in question. In the
days after onset of epidemic keratoconjunctivitis.16 absence of these findings, however, conjunctival scrapings
Pharyngoconjunctival fever is an acute illness character- can be obtained for fluorescent antibody testing or enzyme-
ized by follicular conjunctivitis, pharyngitis, and fever. This linked immunosorbent assay (ELISA), as well as for cultures.
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.
471
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PART vi The Conjunctiva
Section 2 Conjunctivitis
Children with primary herpes ocular infections may have The Flaviviridae are a family of viruses that include yellow
such profuse tearing that topical trifluorothymidine may be fever, dengue, sandfly fever, and West Nile virus. The most
washed out rapidly. In such cases, the use of ganciclovir common eye finding in West Nile viral infection is chorio-
ophthalmic gel 0.15% five times a day to the conjunctival retinitis. Rarely an acute hemorrhagic conjunctivitis with
sac and eyelids may provide better delivery of antiviral bilateral subconjunctival hemorrhages can guide clinicians
therapy. Neonates who develop herpes simplex primary con- toward early diagnosis of West Nile virus while serologic
junctivitis also should receive intravenous treatment with testing is pending.25
acyclovir. Ebola virus is the most important genus of Filoviridae and
EBV may cause a follicular or membranous conjunctivitis is known to cause hemorrhagic fever and coagulopathy with
with or without subconjunctival hemorrhage. The clinical a high mortality rate. Conjunctival injection that is usually
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- patients along with subconjunctival hemorrhage and exces-
nucleosis characterized by fever, sore throat, and lymphade- sive lacrimation.26 Ocular manifestations may aid in the
nopathy. Serologic testing in patients with symptoms of diagnosis.
acute EBV infection manifests elevated IgM and IgG anti-
body levels against viral capsid antigen, and IgG response to Poxviruses
Epstein−Barr early antigen. Antibodies against Epstein−Barr The Poxviridae include variola (smallpox), vaccinia (cowpox),
nuclear antigen do not develop until several weeks or months monkeypox, and molluscum contagiosum. The poxviruses
after the onset of clinical disease. Discrete, granular subepi- are dermatotrophic DNA viruses that cause lesions of the
thelial infiltrates may be seen with overlying punctate epi- eyelids, conjunctiva, and rarely the cornea.22 Ocular compli-
thelial keratitis. The corneal disease from EBV may closely cations have been reported in 5–9% of patients with small-
mimic that seen in adenoviral keratitis.21 pox.27 Variola has been eradicated because of the efforts of
the World Health Organization; however, concerns have
RNA-containing viruses been raised about the use of smallpox as a biological weapon.
Vaccinia virus, used for mass smallpox inoculation,
The Paramyxoviridae include measles, mumps, and Newcastle may be associated with eyelid and conjunctival infection,
disease, all of which are capable of eliciting a follicular con- corneal ulceration, disciform keratitis, iritis, optic neuritis,
junctivitis.22 Measles infection of the eye may result in a and blindness.28 About 10 to 20 patients per million small-
mucopurulent conjunctivitis, mild epithelial keratitis, and pox immunizations develop ocular complications, usually
occasionally the development of whitish Koplik’s spots on through accidental autoinoculation with fingers or fomites
the conjunctiva or semilunar fold. Newcastle disease is from the vaccination site to the eye.28
unique because it is a unilateral follicular conjunctivitis with Monkeypox, like variola and vaccinia, is an orthopox
preauricular adenopathy. It is limited almost exclusively to virus and was first isolated from a colony of sick monkeys.
contact with poultry but is self-limited and does not require The virus is acquired through contact with an animal’s
therapy. blood or through a bite. Secondary attack rates from person-
The Picornaviridae cause an acute hemorrhagic conjuncti- to-person are less than 10%, whereas for smallpox they are
vitis associated with a follicular conjunctivitis, which ini- 70% with a mortality as high as 50%.29 Monkeypox appears
tially affects one eye and rapidly spreads to the other. All as a pustular rash affecting the head, trunk, and extremities.
patients develop a hemorrhagic bulbar conjunctival reaction The rash of monkeypox is exactly like that of smallpox,
that is more pronounced temporally and takes one to two although monkeypox is associated with more lymphade-
weeks to resolve. The causative agents include enterovirus nopathy than is smallpox.29 Unlike varicella, where vesicular
type 70 or coxsackievirus type A24. Preauricular adenopathy lesions are characteristically in different stages of develop-
may be seen in 60% of affected individuals.22 ment and healing, monkeypox lesions are all essentially at
The Orthomyxoviridae include the influenza virus, which the same stage.
may cause severe bronchopneumonia, particularly in elderly Molluscum contagiosum may cause a chronic follicular
people. A follicular conjunctivitis with a mucopurulent dis- conjunctival reaction (see Chronic Conjunctivitis below).
charge may be noted.22
The Togaviridae include the causative agent of rubella and Acute membranous conjunctivitis
the chikungunya virus which is transmitted via the Aedes
mosquito. These viruses cause hyperemia of the conjunctiva, Acute membranous or pseudomembranous conjunctivitis
lid swelling, photophobia, and lacrimation in association develops as fibrin coagulates on the epithelial surface, which
with the development of conjunctival follicles.22,23 may obscure the underlying morphologic response of the
Anterior uveitis is the most common presentation of chi- conjunctiva, making further classification difficult. Acute
kungunya virus with pigmented keratic preciitates, photo- membranous conjunctivitis may be caused by both viral
phobia, and retro-orbital pain.23 Chikungunya virus antigens and bacterial organisms. Adenoviral conjunctivitis caused by
have been detected in keratocytes and in fibroblasts of the iris EKC is now the most common cause, followed by HSV con-
and ciliary body, suggesting direct ocular involvement.24 Chi- junctivitis.22 β-hemolytic streptococci and S. aureus are the
kungunya virus was detected in one-third of corneal donors most common bacterial causes for membranous conjunctivi-
not known to be infected in the context of an outbreak in tis. C. diphtheriae was previously the most common bacterial
islands of the Indian Ocean, suggesting that transmission of cause,6 but is now rarely seen. Nevertheless, because of the
the disease could occur through corneal transplantation.24 potential for bacteria to cause membranous conjunctivitis,
472
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CHAPTER 40
Conjunctivitis: An Overview and Classification
cultures need to be obtained when there is any question studies may be confirmatory for chlamydial or herpes
about the etiology of the infection. Noninfectious causes simplex disease. Gram stain or culture of a scraping may
of membranous conjunctivitis, such as chemical injury, identify Moraxella, which is an unusual bacterial cause of
Stevens−Johnson syndrome, or vernal conjunctivitis, are chronic follicular conjunctivitis. Cultures also can be crucial
readily distinguished, based on the history or associated in establishing a diagnosis of dacryocystitis or canaliculitis.
systemic findings. A conjunctival biopsy may reveal a neoplastic etiology,
identify a noncaseating or foreign body granuloma, or
Chronic Conjunctivitis uncover microorganisms. Immunofluorescence microscopy
of a conjunctival biopsy may confirm suspicion of mucous
In chronic conjunctivitis, the conjunctival morphology and membrane pemphigoid (ocular cicatricial pemphigoid) in
anatomic localization are the most important variables.5 which immunoglobulin or complement may be seen bound
Unlike most causes of acute conjunctivitis, the diseases to the conjunctival basement membrane.
causing chronic conjunctivitis are not usually self-limited.
In contrast to the majority of cases of acute conjunctivitis, Giant papillary 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. and atopic keratoconjunctivitis compose the two primary
Clinical evaluation of a patient with chronic conjunctivi- forms of giant papillary conjunctivitis (GPC). Secondary
tis begins with a detailed history. The onset of chronic con- forms of GPC are related to contact lenses, ocular prostheses,
junctivitis is usually insidious, and the progression of the or exposed sutures. In allergic disorders, such as vernal kera-
disease may be slow. Symptoms generally include ocular toconjunctivitis, giant papillae may measure several milli-
discomfort, conjunctival injection, and perhaps a discharge. meters in diameter and assume a flat top and polygonal
Symptoms of severe pain or photophobia generally suggest shape, giving rise to the description of “cobblestone” papil-
some corneal involvement. Many patients have used a lae. Secondary forms of giant papillae assume a rounder
variety of medications to treat the disorder; therefore, a shape with pale centers. Although these secondary giant
careful medication history is essential. A history of animal papillae may be confused with follicles, the lower fornix is
exposure, trauma, surgery, and foreign travel are all impor- never involved in secondary GPC.
tant considerations.
The clinician should ask the patient to describe ocular Vernal keratoconjunctivitis
discomfort in some detail. Itching is the most prominent
Vernal keratoconjunctivitis (VKC) is a seasonally recurrent,
feature of allergic disease. Irritation that is worse in the
bilateral conjunctival inflammation of youth; boys are
morning may suggest blepharoconjunctivitis, whereas a
affected twice as often as girls. The most prominent symptom
gritty sensation that worsens later in the day may suggest
is itching, which can become worse toward evening and is
keratoconjunctivitis sicca.
exacerbated by rubbing. Tearing is characteristic and macer-
A thorough eye examination is important, but particular
ates the skin about the corner of the eye. A characteristic
attention should be paid to the skin and eyelids. The skin
thick, mucoid, ropy discharge is noted.30
should be examined for signs of atopic dermatitis, seborrheic
Clinically, VKC may be divided into a palpebral and
dermatitis, or rosacea. Preauricular and submandibular
limbal form. These two forms may occur together, although
nodes should be palpated for the presence of lymphade-
the limbal form is more common in blacks. Palpebral VKC
nopathy. The eyelids should be inspected for the loss of
is characterized by the formation of giant papillae on the
eyelashes; the presence of tumors, papillomas, and mollus-
upper pretarsal conjunctiva. The conjunctiva of the lower
cum contagiosum lesions; and for signs of blepharitis. The
eyelid shows a diffuse, fine papillary reaction. In limbal VKC,
lacrimal drainage system should be evaluated for obstructive
both the upper and lower papillary conjunctiva reveal a fine,
disease or for signs of infection. The conjunctiva is examined
diffuse papillary reaction. The limbal form is marked by
carefully for the presence of follicles or foreign bodies, and
thickened, broad, gelatinous opacification of the upper
the upper lid should be everted to examine the pretarsal
limbus. Within the thickened areas are whitish chalklike
conjunctiva. The corneal examination should include the
excrescences called Trantas dots, which are concretions of
use of fluorescein, lissamine green, or rose Bengal dyes, as
eosinophils that may be evanescent. Corneal involvement
well as careful evaluation of any keratitis, vascularization,
may range from a punctate epithelial keratitis to a “vernal
peripheral scarring, or stromal inflammation. Morphologic
ulcer,” which is a sterile shield-shaped epithelial defect at
responses critical to establishing a correct diagnosis include
the junction of the upper and middle third of the cornea.
papillary, giant papillary, follicular, membranous, cicatriz-
The diagnosis of VKC may be made by examination of
ing, and granulomatous responses.
conjunctival scrapings of the upper tarsus. Greater than two
Laboratory investigation may be invaluable in some cases
eosinophils per high-power field is diagnostic of VKC.
of chronic conjunctivitis. Conjunctival scrapings can help
identify inflammatory and infectious microorganisms. The
presence of eosinophils is a reliable indicator of an allergic
Atopic keratoconjunctivitis
disorder such as atopic or vernal keratoconjunctivitis. Unlike VKC, atopic keratoconjunctivitis (AKC) shows no
In chronic chlamydial infection, conjunctival scrapings seasonal variation. Onset is generally during the late teens;
stained with Giemsa may reveal basophilic intracytoplasmic in most cases AKC improves or “burns out” by the fourth or
inclusion bodies within epithelial cells. Immunofluorescent fifth decade.
473
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PART vi The Conjunctiva
Section 2 Conjunctivitis
The lid margins may be indurated and lichenified. Giant or from sebaceous glands in the caruncle. Patients with an
papillary hypertrophy is noted in the upper and lower lids. unexplained unilateral conjunctivitis should undergo biopsy
Corneal scarring and foreshortening of the conjunctival that includes the tarsus and conjunctiva or skin. Sebaceous
fornix may occur secondary to the chronicity of the disorder. cell carcinoma often spreads in a pagetoid fashion within
Conjunctival scrapings reveal mast cells, basophils, eosino- the epithelium, requiring multiple conjunctival biopsies.
phils, and possible lymphocytes.30 Clues to the correct diagnosis include eyelid thickening
and deformity, focal loss of eyelashes, unilateral involve-
Secondary giant papillary conjunctivitis ment, and an abnormal papillary conjunctival inflamma-
tion. A full-thickness wedge biopsy should be performed to
Secondary giant papillary conjunctivitis occurs most com-
definitively diagnose this disorder. Sebaceous cell carcinoma
monly in soft contact lens wearers.30 Patients complain of a
is a life-threatening disorder, and early diagnosis may be
foreign body sensation and ocular discomfort. Mucinous
lifesaving.37
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 Lacrimal drainage system infection
sutures.
Chronic dacryocystitis
Chronic papillary conjunctivitis Chronic dacryocystitis or chronic canaliculitis may lead to
a chronic papillary conjunctivitis secondary to infectious
Chronic papillary conjunctivitis has several different etiolo- organisms. Chronic dacryocystitis occurs in the presence of
gies. Anatomic localization and the differentiation of unilat- lacrimal outflow obstruction distal to the lacrimal sac.38 This
eral or bilateral involvement can be helpful in establishing obstruction causes stasis of tears within the lacrimal sac,
a correct diagnosis.5 which leads to secondary bacterial colonization and infec-
tion. An acute lacrimal sac abscess may develop; however, if
Masquerade syndrome the common canaliculus remains patent, a chronic conjunc-
A chronic, unilateral papillary conjunctivitis should arouse tivitis may develop as purulent material drains in a retro-
the suspicion of a masquerade syndrome caused by an grade fashion. Patients may initially complain of epiphora
underlying ocular surface malignancy. Chronic conjunctival before the onset of chronic conjunctival irritation and a
inflammation may be associated with intraepithelial neopla- mucopurulent discharge. Examination typically reveals a
sia, pigmented or amelanotic melanoma, and sebaceous cell unilateral, diffuse papillary conjunctivitis with a mucopuru-
carcinoma. lent discharge. When pressure is applied over the lacrimal
sac, reflux of purulent material can be observed through the
Intraepithelial neoplasia punctum and is diagnostic of dacryocystitis. The skin overly-
ing the lacrimal sac may be quite tender and swollen. Con-
Squamous dysplasia or intraepithelial neoplasia of the con- junctival cultures are necessary to identify the infectious
junctiva nearly always arises at the limbus and, more com- etiology. Staphylococci and streptococci are the most
monly, in the intrapalpebral area. The lesions appear as common organisms isolated; however, a wide variety of bac-
raised, somewhat gelatinous masses, which may be gray or terial and fungal organisms have been noted. Treatment
slightly red.31 The extent of the lesion is best visualized by involves oral and topical antibiotics. Once the infection
application of rose Bengal dye. Treatment involves conjunc- is resolved, obstruction distal to the lacrimal sac needs to
tival excision and scraping of the epithelial extension onto be further investigated and patency established to avoid
the cornea. The limbus, base, and conjunctival margin are recurrence.
frozen with a retinal cryoprobe in a rapid, double freeze-
thaw manner.32 Chronic canaliculitis
Malignant melanoma Chronic canaliculitis is frequently due to a diverticulum of
the canaliculus in which organisms proliferate. Symptoms
Malignant melanoma can arise in clear conjunctiva in 10% are similar to that of chronic dacryocystitis, except that
of cases, from a pre-existing nevus in 20–30% of cases, or epiphora is absent.38 Examination reveals a papillary con-
from primary acquired melanosis in 60–70% of cases.33,34 It junctivitis with mucopurulent discharge. Frequently, there
is particularly rare before the third decade of life. Clinically, is a discharge from the punctal orifice. The punctum is often
lesions can be pigmented or nonpigmented, are elevated, enlarged and pouts externally. Mechanical expression of
and can affect any portion of the conjunctiva.34 Treatment infected material from the canaliculus is accomplished by
is by wide local excision followed by freeze–thaw–freeze applying pressure using cotton-tipped applicators to both
cryotherapy.34 Topical interferon-alfa has been shown to the inner and outer surfaces of the medial aspect of the
cause regression of conjunctival and corneal melanoma.35 eyelid while rolling the applicators toward the punctum.
Topical mitomycin C may be used as an adjuvant therapy Cheesy concretions may be expressed from the punctum.
for conjunctival melanoma.36 The expressed material should be cultured for aerobic and
anaerobic bacteria and fungi. Gram stain of the exudate
Sebaceous cell carcinoma
often reveals a filamentous, branching, Gram-positive bac-
Sebaceous cell carcinoma arises from meibomian glands terium, which may be identified as Actinomyces israelii, the
most commonly, although it can also develop in Zeis’ glands most common cause of canaliculitis.39
474
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CHAPTER 40
Conjunctivitis: An Overview and Classification
The differential diagnosis of chronic papillary conjuncti- common cause of chronic lid inflammation and is part of a
vitis involving both eyes includes keratoconjunctivitis sicca, generalized sebaceous gland abnormality in which hard, oily
blepharoconjunctivitis, and disorders that specifically have scales may be seen clinging to the eyelashes.
a predilection for the upper palpebral conjunctiva, including
superior limbic keratoconjunctivitis, the floppy eyelid syn- Meibomian gland dysfunction
drome, and a retained foreign body. Meibomian gland dysfunction is characterized by thickening
of the eyelid margin, inspissated and thickened secretions of
Superior limbic keratoconjunctivitis the glands, dilation of the ducts of the glands, a foamy secre-
Superior limbic keratoconjunctivitis is a noninfectious tion on the lid margins, and recurrent chalazia. Not uncom-
inflammatory disease characterized by: (1) velvety papillary monly, meibomian gland dysfunction is associated with
hypertrophy of the upper palpebral conjunctiva; (2) hyper- ocular rosacea. Secondary colonization of meibomian glands
emia and rose Bengal staining of the upper bulbar conjunc- by staphylococcal organisms may further destabilize the tear
tiva; (3) micropannus and punctate rose Bengal staining of film. Treatment of blepharoconjunctivitis includes mechani-
the superior limbus; (4) thickening and keratinization of the cal cleansing of the eyelids, application of warm compresses,
superior limbal, bulbar, and palpebral conjunctiva; and (5) systemic tetracyclines, oral supplementation of essential
superior filamentary keratitis in about 50% of patients.40,41 fatty acids, and use of erythromycin or bacitracin antibiotic
Scrapings of the superior bulbar conjunctiva reveal keratin- ointment.
ized epithelial cells.
Keratoconjunctivitis sicca
Floppy eyelid syndrome The other principal cause of chronic, bilateral papillary con-
The floppy eyelid syndrome is a distinct entity seen more junctivitis is keratoconjunctivitis sicca. This disorder occurs
commonly in obese people and in those who sleep on their when the quantity or quality of the precorneal tear film
stomachs. It is characterized by a rubbery, redundant upper is insufficient to ensure the well-being of the ocular epithe-
tarsus, which everts with minimal pressure. A chronic papil- lial surface.46 Symptoms include ocular discomfort, foreign
lary conjunctivitis is seen over the upper palpebral conjunc- body sensation, and burning, all of which are worsened
tiva and may be associated with corneal changes ranging by wind, smoke, low humidity, and environmental pollut-
from mild punctate keratitis to superficial pannus.42 During ants. Symptoms tend to become worse as the day progresses.
sleep, the upper eyelid is thought to evert, resulting in Clinical signs of keratoconjunctivitis sicca include a decreased
mechanical contact with the pillow or other bed clothes tear lake, mucous debris in the tear film, and corneal and
accounting for the chronic irritation. Treatment consists conjunctival staining with rose Bengal, most prominent
of a protective metal shield or taping the eyelids while in the interpalpebral fissure. Schirmer testing may be per-
asleep. Surgical treatment is directed toward eyelid-tightening formed with or without topical anesthesia. Wetting <5 mm
procedures. when performed without anesthesia is highly specific for
the diagnosis of keratoconjunctivitis sicca.47 Treatment is
Blepharoconjunctivitis directed toward artificial tear substitutes, anti-inflammatory
agents including short-term topical steroids and topical
Bilateral chronic papillary conjunctivitis is most frequently cyclosporine, damming of the lacrimal outflow system, and
caused by blepharoconjunctivitis or keratoconjunctivitis in severe cases, reducing the rate of evaporation through
sicca, which often coexist. Patients with blepharitis com- tarsorrhaphy.
plain of chronic burning, irritation, and foreign body sensa-
tion associated with photophobia if the cornea is involved. Mucus-fishing syndrome
Symptoms are frequently worse early in the morning. Bleph-
aritis may be classified as (1) staphylococcal/Demodex, A mechanically induced, chronic papillary conjunctivitis
(2) seborrheic, and (3) meibomian, although patients with has been described in patients with various underlying,
blepharitis frequently exhibit signs from more than one external ocular diseases, including keratoconjunctivitis sicca,
category.43 blepharitis, and allergic conjunctivitis. These patients exac-
erbate their conjunctival irritation by the frequent mechani-
Staphylococcal/Demodex and seborrheic cal removal of excess mucus from the surface of the globe
or from the inferior fornix. The entity has been called the
Staphylococcal, Demodex and seborrheic forms are frequently
“mucus-fishing” syndrome and exacerbates the findings in
categorized as “anterior blepharitis,” whereas meibomian
external ocular diseases in which the treatment might
gland dysfunction is characterized as “posterior blepharitis.”
otherwise be appropriate.48
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
Toxic papillary keratoconjunctivitis
from which the term collarette is derived. Demodex is a Toxic papillary keratoconjunctivitis is the most common of
microscopic mite that is the most common permanent ecto- all adverse reactions to topical medications.49 The toxic
parasite of humans.44 Demodex infestation has been highly effects usually take at least two weeks to develop. Punctate
correlated with cylindrical dandruff on the lashes and is staining, best identified with rose Bengal dye, is more pro-
thought to be a cause of anterior blepharitis and allergic nounced on the inferonasal conjunctiva and cornea where
conjunctivitis.45 Seborrheic blepharitis is probably the most medications gravitate on their way to the lacrimal outflow
475
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PART vi The Conjunctiva
Section 2 Conjunctivitis
476
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CHAPTER 40
Conjunctivitis: An Overview and Classification
477
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PART vi The Conjunctiva
Section 2 Conjunctivitis
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