Key Features
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Infectious causes may be bacterial, fungal parasitis, or viral.
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Infectious conjunctivitis can be classified by duration of symptoms.
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The diagnosis is usually made clinically. If the diagnosis is not readily apparent, laboratory studies may be helpful in determining etiology.
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May be noninfectious causes of conjunctivitis.
Infectious Conjunctivitis
Bacterial Infections
Bacterial conjunctivitis is characterized by a rapid onset of unilateral conjunctival hyperemia, lid edema, and mucopurulent discharge. The second eye typically becomes involved 1–2 days later.
The pathogenesis of bacterial conjunctivitis usually involves a disruption of the host defense mechanisms, for example, abnormalities of the ocular surface secondary to eyelid abnormalities, tear film abnormalities, or systemic immunosuppression. Bacterial conjunctivitis can be classified into three clinical types: acute, hyperacute, and chronic (see Table 4.6.1 for a list of common pathogens).
| Acute | Hyperacute | Chronic |
|---|---|---|
| Staphylococcus aureus | Neisseria gonorrhoeae | Staphylococcus aureus |
| Streptococcus pneumoniae | Neisseria meningitidis | Moraxella lacunata |
| Haemophilus influenzae | Enteric bacteria |
Conjunctival membranes and pseudo-membranes may occur in bacterial conjunctivitis in association with Neisseria gonorrhoeae , β -hemolytic streptococci , and Corynebacterium diphtheria . Pseudo-membranes, which include inflammatory cells and an exudate containing mucus and proteins, are loosely adherent to the underlying conjunctival epithelium and can be peeled away with no bleeding or damage to the epithelium. True membranes occur with more intense inflammation. The conjunctival epithelium becomes necrotic, and firmer adhesions are formed between the necrotic cells and the overlying coagulum. When the membrane is peeled, the epithelium tears to leave a raw, bleeding surface.
Acute Bacterial Conjunctivitis
Acute bacterial conjunctivitis usually begins unilaterally with hyperemia, irritation, tearing, mucopurulent discharge, and mattering of the lids ( Fig. 4.6.1 ). Punctate epithelial keratitis also may occur. The most common pathogens include Staphylococcus aureus , Streptococcus pneumoniae , and Haemophilus influenzae. Other common ocular manifestations include blepharitis, keratitis, marginal ulcers, and phlyctenulosis. The pathogens H. influenzae , S. pneumoniae , and Moraxella catarrhalis occur more commonly in young children and may occur in institutional epidemics. H. influenzae is often associated with systemic infection, including upper respiratory infections, and acute otitis media.
The treatment of acute bacterial conjunctivitis consists of topical antibiotic drops or ointments. Although these infections normally are self-limiting, lasting 7–10 days, antibiotic therapy usually speeds the resolution and lessens the severity of the disease. A broad-spectrum antibiotic with good Gram-positive coverage, such as a third- or fourth-generation fluoroquinolone, 10% sodium sulfacetamide, or trimethoprim-polymyxin, may be used for 7–10 days.
Hyperacute Bacterial Conjunctivitis
The most common cause of hyperacute bacterial conjunctivitis is N. gonorrhoeae. This oculogenital disease is seen primarily in neonates and sexually active young adults. Transmission is by contact with infected urine or genital secretions. Symptoms develop within 24 hours, and signs include profuse, thick, yellow-green purulent discharge, painful hyperemia, chemosis of the conjunctiva, and tender preauricular nodes. Untreated cases may lead to peripheral corneal ulceration and eventual perforation with possible endophthalmitis. A similar, but milder form of conjunctival and corneal disease is caused by primary or secondary infection with Neisseria meningitides . Primary meningococcal conjunctivitis is extremely rare in adults and can be invasive (followed by systemic meningococcal disease) or noninvasive (isolated conjunctival infection). If invasive disease is present, close contacts should receive prophylaxis with a single dose of ciprofloxacin 500 mg or rifampin 600 mg twice daily for 2 days.
Treatment is directed at the specific pathogen. Conjunctival scraping for Gram staining and culture on blood and chocolate agar are strongly recommended. Gram-negative diplococci are suggestive of Gonococcus . An effective regimen for gonococcal conjunctivitis is a single dose of 1 g of intramuscular ceftriaxone. If a corneal ulcer is present, hospitalization with 1 g intravenous ceftriaxone for 3 days is recommended. Topical medications may include bacitracin, ciprofloxacin, or erythromycin ointment every 1–2 hours. Frequent irrigation, every 30–60 minutes, with normal saline or balanced salt solution, also is recommended. Adults are often treated empirically for concurrent chlamydial infection with azithromycin 1 g once or doxycycline 100 mg twice a day for 7 days. In meningococcal conjunctivitis, systemic treatment includes intravenous penicillin, or for penicillin-resistant infections, intravenous cefotaxime or ceftriaxone. Patients need to be seen daily to rule out corneal involvement.
Chronic Bacterial Conjunctivitis
Chronic bacterial conjunctivitis, lasting longer than 3 weeks, may result from a number of organisms and is often associated with blepharitis. The most common organisms are S. aureus and Moraxella lacunata ; other causative organisms include the enteric bacteria Proteus mirabilis , Escherichia coli , Klebsiella pneumoniae , Serratia marcescens , and Branhamella catarrhalis from the upper respiratory tract. The most common causative agent is S. aureus , which colonizes the eyelid margin and then causes direct infection of the conjunctiva or conjunctival inflammation through its elaboration of exotoxins. Chronic angular blepharoconjunctivitis of the inner and outer canthal angles most commonly results from M. lacunata . A chronic follicular conjunctivitis may accompany both types.
The clinical signs of chronic staphylococcal conjunctivitis include diffuse conjunctival hyperemia with papillae or follicles, minimal mucopurulent discharge, and conjunctival thickening. Erythema of the eyelid, telangiectasis, lash loss, collarettes, recurrent hordeolae, and ulcerations at the base of the cilia can be seen. The cornea may demonstrate marginal corneal ulcers ( Fig. 4.6.2 ).
Treatment combines proper antimicrobial therapy and good lid hygiene, which includes warm compresses and eyelid scrubs. Azithromycin drops and erythromycin or bacitracin ointments are effective adjunctive topical antibiotics. When severe inflammation exists, antibiotic and corticosteroid combination drops or ointments can be rubbed into the lid margins after the lid scrubs. Oral therapy with tetracycline 250 mg four times a day, doxycycline 100 mg one to two times a day, or minocycline 50 mg one to two times a day may be needed for more severe infections.
Adenoviral Conjunctivitis
Viral conjunctivitis is extremely common. The diagnosis usually can be made clinically. Many different viruses cause conjunctivitis, and each produces a slightly different disease.
Adenoviruses produce the most common viral conjunctivitides with varying degrees of severity. The spectrum consists of follicular conjunctivitis, pharyngoconjunctival fever, and epidemic keratoconjunctivitis. These infections are spread via respiratory droplets or direct contact from fingers to the lids and conjunctival surface. The incubation period is usually 5–12 days and the clinical illness is present for 5–15 days.
Follicular Conjunctivitis
Follicular conjunctivitis is the mildest form and is associated with adenovirus serotypes 1 through 11 and 19. It has an acute onset and is initially unilateral with possible involvement of the second eye within 1 week. It is manifested by a watery discharge and conjunctival hyperemia and usually is accompanied by follicular and papillary conjunctival changes with preauricular lymphadenopathy on the affected side. Most cases resolve spontaneously, without sequelae, within days to weeks.
Pharyngoconjunctival Fever
Pharyngoconjunctival fever is the most common ocular adenoviral infection and is produced by adenovirus serotypes 3, 4, and 7. It is characterized by a combination of pharyngitis, fever, and conjunctivitis ( Fig. 4.6.3 ). The conjunctivitis is predominantly follicular with a scant watery discharge, hyperemia, and mild chemosis. The cornea may be involved with a fine punctate epitheliopathy. Preauricular lymph nodes are enlarged in about 90% of cases. The disease resolves spontaneously within 2 weeks, so treatment is usually supportive with cold compresses, artificial tears, and judicious use of vasoconstrictor eyedrops.
Epidemic Keratoconjunctivitis
Epidemic keratoconjunctivitis (EKC) is produced by adenovirus serotypes 8, 19, and 37. It is a more severe type of conjunctivitis and typically lasts for 7–21 days. EKC produces a mixed papillary and follicular response of the conjunctival stroma with a watery discharge, hyperemia, chemosis, and ipsilateral preauricular lymphadenopathy ( Fig. 4.6.4 ). Subconjunctival hemorrhages, conjunctival membrane formation, and lid edema are common (see Fig. 4.6.4 ; Fig. 4.6.5 ). Histologically, these conjunctival membranes consist of fibrin and leukocytes with occasional fibroblast infiltration. Both true membranes and pseudo-membranes may occur, and conjunctival scarring and symblepharon formation may follow their resolution.
Corneal involvement is variable. Most patients have a diffuse, fine, superficial keratitis within the first week of the disease. Focal, elevated, punctate epithelial lesions that stain with fluorescein develop by days 6–13 ( Fig. 4.6.6 ), producing a foreign body sensation. By day 14, subepithelial opacities develop under the focal epithelial lesions in 20%–50% of cases ( Fig. 4.6.7 ). These opacities often are visually disabling and may persist for months to years, but eventually they resolve with no scarring or vascularization. The diagnosis of EKC is made clinically, but a rapid immunodetection assay (RPS Adeno Detector; Rapid Pathogen Screening; South Williamsport, PA) is now available and is capable of detecting all 53 adenoviral serotypes with a reported sensitivity of 89% and specificity of 94%.
Treatment aims at alleviation of symptoms and minimization of transmission of this highly contagious disease. Patients may be infectious for up to 14 days after onset, and outbreaks are especially common in ophthalmology offices and clinics. Transmission usually occurs from eye to fingers to eye; tonometers, contact lenses, and eyedrops are other routes of transmission. Preventive measures include frequent hand washing, relative isolation of infected individuals in an office setting, and disinfection of ophthalmic instruments. During the stage of acute conjunctivitis, treatment usually is supportive and includes cold compresses and decongestant eyedrops. When patients have decreased visual acuity or disabling photophobia from subepithelial opacities, topical corticosteroid therapy may be beneficial. High-dose topical corticosteroids, such as 1% prednisolone acetate three to four times a day, or difluprednate twice a day, can help eliminate subepithelial infitrates. However, some believe that use of topical corticosteroids prolongs viral shedding and worsen symptoms if the infectious virus is herpes simplex. Cidofovir, an antiviral agent, has been investigated in the treatment of EKC. Although the application of cidofovir drops may prevent the formation of corneal opacities, use has been limited by local toxicity and commercial unavailability. Others have advocated the use of topical gancyclovir. Currently, the utility of a povidone-iodine 0.4%/dexamethasone 0.1% combination ophthalmic suspension is being investigated.
Acute Hemorrhagic Conjunctivitis
Acute hemorrhagic conjunctivitis, also known as Apollo disease , was first described in Ghana in 1969. Two picornaviruses, enterovirus 70 and coxsackievirus A24, are the usual causative agents. Less commonly, it is caused by adenovirus type 11. A rapid onset of severe, painful follicular conjunctivitis occurs, with chemosis, tearing, lid edema, and tiny subconjunctival hemorrhages. The hemorrhages are petechial at first and then coalesce, appearing posttraumatic. The cornea may demonstrate a fine punctate keratopathy and, rarely, subepithelial opacities. The conjunctivitis resolves within 4–6 days, but the hemorrhages clear more slowly. The disease occurs in epidemics, especially in developing countries, with more than 50% of the local population affected in some cases. Very rarely, cases caused by enterovirus type 70 can result in a polio-like paralysis, which remains permanent in up to one third of affected individuals.
Herpes Simplex Conjunctivitis
Primary herpes simplex conjunctivitis usually occurs in children under 5 years of age. Most cases are undocumented because of their nonspecific nature. Typical signs include ocular irritation, watery discharge, mixed papillary and follicular conjunctivitis, hemorrhagic conjunctivitis, and preauricular lymphadenopathy. Most cases are unilateral but may become bilateral. Epidermal vesicular eruptions of the eyelids and lid margins may accompany the conjunctivitis ( Fig. 4.6.8 ), and the cornea may be involved. Corneal involvement may include a coarse, punctate epithelial keratitis, marginal infiltrates, or a dendritic ulcer. Although herpetic blepharoconjunctivitis is associated mainly with the primary disease, it may occur as a manifestation of recurrent disease with or without typical herpetic keratitis. Most ocular herpetic infections result from herpes simplex virus type 1. Infections that result from the type 2 serotype may be seen in newborns or adults who have a history of oral–genital contact.
The conjunctivitis usually resolves spontaneously in 7–14 days without treatment, although some physicians administer topical antiviral drops to patients with corneal involvement or to patients with lid vesicles, with the goal of preventing corneal involvement. Care should be taken to avoid the cavalier use of corticosteroids in the treatment of patients who have an acute follicular conjunctivitis because some of these patients may have herpetic disease and corticosteroids may enhance the severity of herpetic epithelial keratitis.
Other Causes of Viral Conjunctivitis
Other causes of viral conjunctivitis include the rubella, rubeola, varicella-zoster, Epstein–Barr virus infection, Newcastle disease, and Zika virus infections. Rubella virus produces a nondescript, catarrhal follicular conjunctivitis associated with the systemic disease. Rubeola produces a catarrhal, papillary conjunctivitis with tearing, pain, and photophobia. Pale, discrete, avascular spots, which resemble Koplik’s spots seen in the mouth, may appear on the conjunctiva. Varicella-zoster virus produces pustules and phlyctenule-like lesions on the conjunctiva, and a follicular conjunctivitis may occur with recurrent skin disease. Follicular conjunctivitis associated with the Epstein–Barr virus occurs in association with infectious mononucleosis. Newcastle disease viral conjunctivitis occurs in poultry workers and veterinarians in whom direct conjunctival inoculation of the virus has occurred while handling infected birds. The disease is self-limiting, lasts 7–10 days, and leaves no ocular sequelae. Zika virus is a mosquito-borne infection that has led to many outbreaks in Africa and Asia, and most recently, in 2015, it has reached the Americas. The virus may present with fever, rash, arthralgia, and conjunctivitis in approximately 20% of cases. Symptoms are generally self-limiting, although fetal transmission may lead to brain defects.
Chronic Follicular Conjunctivitis
Chronic follicular conjunctivitis lasts more than 16 days ( Box 4.6.1 ). Chlamydia trachomatis , an obligate intracellular bacterium, is the most common cause; it causes three clinical syndromes—trachoma, adult inclusion conjunctivitis, and neonatal conjunctivitis.
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Chlamydiasis
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Trachoma
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Adult inclusion conjunctivitis
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Molluscum contagiosum
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Drug-induced or toxic conjunctivitis
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Bacterial conjunctivitis
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Axenfeld’s chronic follicular conjunctivitis
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Merrill–Thygeson-type follicular conjunctivitis
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Parinaud’s oculoglandular syndrome
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Folliculosis of childhood
Trachoma
Trachoma, which results from C. trachomatis serotypes A to C, is endemic in many parts of the world, including Africa, the Middle East, Latin America, Central Asia, and South-East Asia. Current reports indicate that active trachoma affects approximately 150 million people worldwide, with about 10 million people developing secondary trichiasis and approximately 6 million blinded from sequelae of the disease. After an incubation period of 5–10 days, trachoma manifests as a mild, mucopurulent conjunctivitis that is typically self-limiting and heals without permanent sequelae. Repeated infections, however, result in chronic inflammation, including follicular conjunctivitis and papillary hypertrophy of the upper palpebral conjunctiva, a superior superficial corneal pannus, and fine epithelial keratitis. Eventually, multiple reinfections lead to scarring and cicatrization of the cornea, conjunctiva, and eyelids.
The trachoma complications that cause blindness occur as a result of corneal ulceration, severe conjunctival scarring, and eyelid deformities with their concomitant effects on the ocular surface. Arlt’s line (a horizontal line that results from conjunctival scarring at the junction of the anterior one third and posterior two thirds of the conjunctiva) is a characteristic finding on the superior pretarsal conjunctiva. Herbert’s pits are a unique sequelae of trachoma ; these sharply delineated depressions occur after necrosis and cicatrization of limbal follicles, and the resultant clear space is filled with epithelium. A diffuse haze of the superior cornea may result after regression of the superior pannus. Eyelid deformities, such as trichiasis, distichiasis, entropion, and ectropion, all may occur. Corneal complications, including scarring, vascularization, ulceration, and perforation, lead to decreased visual acuity and possible blindness.
Treatment of trachoma usually consists of a 3- to 4-week course of oral tetracycline (tetracycline 1 g/day or doxycycline 100 mg/day) or oral erythromycin. The clinical response may be slow and take 9–18 weeks to be seen. More recently, a single 20 mg/kg dose of oral azithromycin has been shown in several randomized controlled trials to be as effective as 6 weeks of topical tetracycline. Topical azithromycin 1.5% twice daily for 2–3 days has also been found to be as effective as the single oral dose with a low recurrence rate. Widespread repeated use of systemic antibiotics in endemic areas has been tried in an attempt to eradicate the disease with slow resolution of active trachoma.
Adult Inclusion Conjunctivitis
Adult inclusion conjunctivitis results from C. trachomatis serotypes D to K. It presents as a unilateral red eye with mucopurulent discharge, marked hyperemia, papillary hypertrophy, and a predominant follicular conjunctivitis. A tender, enlarged preauricular lymph node is common. Women often have a concomitant vaginal discharge secondary to a chronic cervicitis, and men may have symptomatic or asymptomatic urethritis. The conjunctivitis is often chronic, lasting many months. Keratitis may develop 1 week after onset. Corneal involvement includes a superficial punctate keratitis, small marginal or central infiltrates, EKC-like subepithelial infiltrates, limbal swelling, and a superior limbal pannus. The untreated disease has a chronic course, and keratitis or iritis can occur in the later stages of the disease.
Diagnosis is based on the clinical appearance plus laboratory test results. Basophilic intracytoplasmic epithelial inclusions are seen with Giemsa staining of conjunctival scrapings ( Fig. 4.6.9 ). Immunofluorescent staining of the conjunctival scrapings is also useful. Serum immunoglobulin G titers to Chlamydia may be obtained.
The modes of transmission include orogenital activities and hand-to-eye spread of infective genital secretions. The incubation period is 4–12 days. One in 300 patients who have genital chlamydial disease develops adult inclusion conjunctivitis. It is important to treat all sexual partners simultaneously to prevent reinfection and also to rule out other venereal diseases, such as gonorrhea and syphilis. Treatment consists of systemic antibiotics, as topical antibiotics are relatively ineffective in the treatment of the eye disease. A single 1-g dose of azithromycin or doxycycline 100 mg twice a day for 7 days is the recommended treatment. Tetracyclines should be avoided in children younger than 7 years of age and in pregnant or lactating women.
Neonatal Conjunctivitis (Ophthalmia Neonatorum)
Conjunctivitis of the newborn is defined as any conjunctivitis that occurs within the first month of life ( Table 4.6.2 ). It may be a bacterial, viral, or chlamydial infection or a toxic response to topically applied chemicals. Because the infectious agent may produce a severe localized infection of the eye plus a potentially serious systemic infection, precise identification of the cause is essential.
| Causes | Time of Onset (Postpartum) |
|---|---|
| Chemical (povidone-iodine) | 1–36 hours |
| Chlamydia | 5–14 days |
| Neisseria gonorrhoeae | 24–48 hours |
| Bacteria ( Staphylococcus , Streptococcus , Haemophilus , Moraxella , Escherichia coli, Pseudomonas ) | 2–5 days |
| Virus (herpes simplex virus types 1 and 2) | 3–15 days |
Not all infants exposed to infectious agents in the birth canal develop conjunctivitis; the duration of the exposure is an important factor in the development of disease. Prevention with good prenatal care and treatment of chlamydial, gonococcal, or herpetic infections during pregnancy significantly lower the incidence of neonatal conjunctivitis. Proper eye cleaning using sterile cotton followed by the instillation of erythromycin or tetracycline antibiotic ointments immediately after birth helps prevent neonatal ocular infection. Previous studies suggested that instillation of 2.5% povidone-iodine as prophylaxis has superior bactericidal effects and also is active against viruses, most notably herpes simplex. However, recent studies suggest topical tetracycline and erythromycin ointment may be more effective in prevention of ophthalmia neonatorum given that 5%–10% of patients treated with povidone-iodine developed a chemical conjunctivitis.
Chlamydial Infections
The most frequent cause of neonatal conjunctivitis in the United States is C. trachomatis . Infants whose mothers have untreated chlamydial infections have a 30% –40% chance of developing conjunctivitis and a 10%–20% chance of developing pneumonia. Symptoms typically develop 5–14 days after delivery and may be unilateral or bilateral. Initially, infants have a watery discharge that may progressively turn mucopurulent. Signs include lid edema, a papillary conjunctival response, and pseudo-membrane formation ( Fig. 4.6.10 ). Usually, the infection is mild and self-limiting; severe cases, however, may occur and result in conjunctival scarring and a peripheral corneal pannus with corneal scarring. If either erythromycin or tetracycline ointment is applied within 1 hour of delivery, the chance of developing chlamydial conjunctivitis is markedly decreased.
Laboratory data are very helpful in the diagnosis. Enzyme-linked immunosorbent assay is nearly 90% sensitive and over 95% specific and provides results within several hours. A direct immunofluorescent monoclonal antibody stain of conjunctival smears is the most useful serological test because it has over 95% sensitivity and 77%–90% specificity for Chlamydia , depending on the prevalence of the disease. It may show infections missed by other assays and can be read immediately. Polymerase chain reaction (PCR) and ligase chain reaction also are available and are approximately 90% sensitive and 100% specific.
Topical therapy alone is not sufficient to treat chlamydial conjunctivitis. The recommended treatment is oral erythromycin syrup 50 mg/kg/day in four divided doses for 14 days ( Table 4.6.3 ). If complete response does not occur, a second course of the same therapy may be given. The mother and her sexual partners should be treated with oral azithromycin 1 g in a single dose or oral amoxicillin 500 mg three times daily for 7 days.
| Infection | Treatment |
|---|---|
| Chlamydia | Oral erythromycin 50 mg/kg/day in four divided doses for 14 days |
| Bacteria | |
| Gram-positive | Erythromycin 0.5% ointment four times a day |
| Gram-negative, gonococcal | Intravenous or intramuscular ceftriaxone 25–50 mg/kg single dose |
| Gram-negative, others | Gentamicin or tobramycin ointments |
| Viral | Trifluorothymidine drops every 2 hours for 7 days |
Neisserial Infections
Neonatal conjunctivitis caused by N. gonorrhoeae , a Gram-negative diplococcus that can penetrate an intact epithelium, has decreased significantly since the advent of prophylactic agents. The clinical picture of gonococcal conjunctivitis consists of the development of a hyperacute conjunctivitis 24–48 hours after birth characterized by marked eyelid edema, profound chemosis, and excessive purulent discharge. The discharge often is so copious that it reaccumulates immediately after the eye has been wiped clean. Conjunctival membrane formation may occur. Because the organism may penetrate an intact epithelium, corneal ulceration with possible perforation can occur if the conjunctivitis is not treated adequately.
Diagnosis is made by identification of Gram-negative intracellular diplococci on conjunctival smears. The organism is best cultured on chocolate agar or Thayer–Martin agar incubated at 37 °C in 10% carbon dioxide, and sensitivities should be obtained. Prompt diagnosis by examination of immediate Gram staining is essential to timely and effective therapy.
Local treatment consists of aqueous penicillin G drops 10 000–20 000 units. Drops are given every hour with a loading dose of one drop every 5 minutes for 30 minutes. Systemic therapy also should be instituted with intravenous or intramuscular ceftriaxone 25–50 mg/kg in a single dose (see Table 4.6.3 ). For disseminated disease, consultation with an infectious disease specialist is recommended. The mother and her sexual partners should be treated with intramuscular ceftriaxone 250 mg in a single dose.
Other Bacterial Infections
Many different organisms can cause bacterial neonatal conjunctivitis. Bacteria are probably transmitted through the air to the infant shortly after birth and may be associated with nasolacrimal duct obstruction. These infections are usually caused by Gram-positive bacteria ( S. aureus , S. epidermidis , S. pneumoniae , and S. viridans ). Gram-negative organisms that have been implicated include Haemophilus species, E. coli , Proteus species, K. pneumoniae , Enterobacter species, and Serratia marcescens. Rarely, pseudomonas sp. causes corneal ulceration and perforation.
Typically, these infections arise 2–5 days after birth. Signs include lid edema, chemosis, and conjunctival injection with discharge. The work-up includes conjunctival scrapings for Gram staining and cultures, the results of which direct the choice of therapy. For Gram-positive organisms, erythromycin 0.5% ointment four times a day is administered. Gentamicin, tobramycin, or fluoroquinolone drops or ointment four times a day can be used for Gram-negative organisms (see Table 4.6.3 ).
Viral Infections
Viral conjunctivitis of the newborn is rare but can be associated with significant morbidity and mortality. Both herpes simplex virus type 1 and herpes simplex type 2 can be associated with conjunctivitis, but type 2 infection is more common. Type 1 may be transmitted by a kiss from an adult who has an active “cold sore,” and type 2 is more commonly transmitted through the birth canal. Onset is usually within the first 2 weeks of life and may be associated with vesicular skin lesions of the lid or lid margin (see Fig. 4.6.8 ). The conjunctivitis may be followed by herpetic keratitis or keratouveitis. Vitritis, retinitis, retinal detachment, optic neuritis, and cataract all have been reported in association with neonatal ocular herpes. The diagnosis may be confirmed by the presence of eosinophilic intranuclear inclusions on smears, positive viral culture results, or positive results from monoclonal antibody immunoassays.
Treatment consists of trifluoridine 1% drops every 2 hours for 7 days, acyclovir ointment five times a day, or ganciclovir drops five times a day (see Table 4.6.3 ). Herpes simplex type 2 may be more resistant to treatment. In cases of systemic disease associated with pneumonitis, septicemia, and meningitis, systemic acyclovir or valcyclovir should be used. Good prenatal care and frequent culture and treatment of mothers who have known herpes genital infections decrease the incidence of herpetic neonatal conjunctivitis.
Fungal and Parasitic Conjunctivitis
Focal eyelid or conjunctival granulomas can be caused by rare infections, including blastomycosis, sporotrichosis, rhinosporidiosis, cryptococcosis, leishmaniasis, and ophthalmomyiasis.
Microsporidial Keratoconjunctivitis
Microsporidae are obligate, intracellular, spore-forming protozoan parasites that can cause disseminated disease or localized keratoconjunctivitis. It is more commonly seen in immunocompromised patients but has been reported in immunocompetent patients with contact lens use, trauma, prior refractive surgery, or exposure to contaminated water or soil. Clinical symptoms include pain, redness, and, occasionally, visual blurring. Superficial, multifocal, coarse, punctate epithelial keratitis, and a diffuse papillary conjunctivitis are typical. Diagnosis is made with ocular surface scraping and the visualization of acid-fast spores in conjunctival epithelial cells upon staining with modified trichrome, potassium hydroxide plus calcofluor white, or Gram stain. Confocal microscopy demonstrates spores that are hyperreflective dots. Electron microscopy is the gold standard for diagnosis. Treatment includes topical fumagillin and oral albendazole or itraconazole. Topical fluoroquinolones are effective as monotherapy.
Loiasis
Loa loa is a filarial nematode that is transmitted from human to human by the bite of an infected female deer fly (genus Chrysops ) that is indigenous to West and Central Africa. The adult worm can migrate subcutaneously from the bite area to the eye. Skin manifestations and conjunctivitis can be present. Extraction of the filarial worm is curative. Treatment consists of diethylcarbamazine 2 mg/kg three times daily for 3 weeks. Ivermectin 150 mg/kg can be used, but significant side effects include subconjunctival and retinal hemorrhages and retinal “cottonwool” spots. Concurrent corticosteroids and/or antihistamines can be used to decrease the side effects of treatment.
Parinaud’s Oculoglandular Syndrome
Parinaud’s oculoglandular syndrome is an uncommon granulomatous conjunctivitis seen in approximately 5%–10% of patients with systemic infection caused by Bartonella henselae (cat scratch disease). B. henselae are small, fastidious Gram-negative rods that affect approximately 22 000 patients in the United States per year. Ocular symptoms include unilateral redness, epiphora, foreign body sensation, and mild lid swelling. Serous discharge may be present; if an abscess forms and ruptures, purulent discharge may be noted. Granulomatous nodules develop on the palpebral and bulbar conjunctiva approximately 3 days after inoculation ( Fig. 4.6.11 ). Necrosis and ulceration of the overlying epithelium is common. Firm and tender regional lymphadenopathy of the preauricular, submandibular, and, occasionally, cervical nodes are a hallmark of the disease ( Fig. 4.6.12 ). Optic neuroretinitis and multifocal chorioretinitis may develop. Diagnosis can be made by indirect immunofluorescence antibody testing or by enzyme immunoassay. Serological testing includes cultures and PCR.
The course of the disease in immunocompetent patients is usually self-limiting, and the disease resolves without antibiotic therapy. Therapy is recommended for immunocompromised patients. Currently recommended therapies include oral erythromycin, doxycycline, or azithromycin. In adults, doxycycline 100 mg twice daily is thought to be more effective because of its superior intraocular and central nervous system penetration. In more severe infections, these medications can be given intravenously, and rifampin can be used as an adjuvant.
Bacterial Infections
Bacterial conjunctivitis is characterized by a rapid onset of unilateral conjunctival hyperemia, lid edema, and mucopurulent discharge. The second eye typically becomes involved 1–2 days later.
The pathogenesis of bacterial conjunctivitis usually involves a disruption of the host defense mechanisms, for example, abnormalities of the ocular surface secondary to eyelid abnormalities, tear film abnormalities, or systemic immunosuppression. Bacterial conjunctivitis can be classified into three clinical types: acute, hyperacute, and chronic (see Table 4.6.1 for a list of common pathogens).
| Acute | Hyperacute | Chronic |
|---|---|---|
| Staphylococcus aureus | Neisseria gonorrhoeae | Staphylococcus aureus |
| Streptococcus pneumoniae | Neisseria meningitidis | Moraxella lacunata |
| Haemophilus influenzae | Enteric bacteria |
Conjunctival membranes and pseudo-membranes may occur in bacterial conjunctivitis in association with Neisseria gonorrhoeae , β -hemolytic streptococci , and Corynebacterium diphtheria . Pseudo-membranes, which include inflammatory cells and an exudate containing mucus and proteins, are loosely adherent to the underlying conjunctival epithelium and can be peeled away with no bleeding or damage to the epithelium. True membranes occur with more intense inflammation. The conjunctival epithelium becomes necrotic, and firmer adhesions are formed between the necrotic cells and the overlying coagulum. When the membrane is peeled, the epithelium tears to leave a raw, bleeding surface.
Acute Bacterial Conjunctivitis
Acute bacterial conjunctivitis usually begins unilaterally with hyperemia, irritation, tearing, mucopurulent discharge, and mattering of the lids ( Fig. 4.6.1 ). Punctate epithelial keratitis also may occur. The most common pathogens include Staphylococcus aureus , Streptococcus pneumoniae , and Haemophilus influenzae. Other common ocular manifestations include blepharitis, keratitis, marginal ulcers, and phlyctenulosis. The pathogens H. influenzae , S. pneumoniae , and Moraxella catarrhalis occur more commonly in young children and may occur in institutional epidemics. H. influenzae is often associated with systemic infection, including upper respiratory infections, and acute otitis media.
The treatment of acute bacterial conjunctivitis consists of topical antibiotic drops or ointments. Although these infections normally are self-limiting, lasting 7–10 days, antibiotic therapy usually speeds the resolution and lessens the severity of the disease. A broad-spectrum antibiotic with good Gram-positive coverage, such as a third- or fourth-generation fluoroquinolone, 10% sodium sulfacetamide, or trimethoprim-polymyxin, may be used for 7–10 days.
Hyperacute Bacterial Conjunctivitis
The most common cause of hyperacute bacterial conjunctivitis is N. gonorrhoeae. This oculogenital disease is seen primarily in neonates and sexually active young adults. Transmission is by contact with infected urine or genital secretions. Symptoms develop within 24 hours, and signs include profuse, thick, yellow-green purulent discharge, painful hyperemia, chemosis of the conjunctiva, and tender preauricular nodes. Untreated cases may lead to peripheral corneal ulceration and eventual perforation with possible endophthalmitis. A similar, but milder form of conjunctival and corneal disease is caused by primary or secondary infection with Neisseria meningitides . Primary meningococcal conjunctivitis is extremely rare in adults and can be invasive (followed by systemic meningococcal disease) or noninvasive (isolated conjunctival infection). If invasive disease is present, close contacts should receive prophylaxis with a single dose of ciprofloxacin 500 mg or rifampin 600 mg twice daily for 2 days.
Treatment is directed at the specific pathogen. Conjunctival scraping for Gram staining and culture on blood and chocolate agar are strongly recommended. Gram-negative diplococci are suggestive of Gonococcus . An effective regimen for gonococcal conjunctivitis is a single dose of 1 g of intramuscular ceftriaxone. If a corneal ulcer is present, hospitalization with 1 g intravenous ceftriaxone for 3 days is recommended. Topical medications may include bacitracin, ciprofloxacin, or erythromycin ointment every 1–2 hours. Frequent irrigation, every 30–60 minutes, with normal saline or balanced salt solution, also is recommended. Adults are often treated empirically for concurrent chlamydial infection with azithromycin 1 g once or doxycycline 100 mg twice a day for 7 days. In meningococcal conjunctivitis, systemic treatment includes intravenous penicillin, or for penicillin-resistant infections, intravenous cefotaxime or ceftriaxone. Patients need to be seen daily to rule out corneal involvement.
Chronic Bacterial Conjunctivitis
Chronic bacterial conjunctivitis, lasting longer than 3 weeks, may result from a number of organisms and is often associated with blepharitis. The most common organisms are S. aureus and Moraxella lacunata ; other causative organisms include the enteric bacteria Proteus mirabilis , Escherichia coli , Klebsiella pneumoniae , Serratia marcescens , and Branhamella catarrhalis from the upper respiratory tract. The most common causative agent is S. aureus , which colonizes the eyelid margin and then causes direct infection of the conjunctiva or conjunctival inflammation through its elaboration of exotoxins. Chronic angular blepharoconjunctivitis of the inner and outer canthal angles most commonly results from M. lacunata . A chronic follicular conjunctivitis may accompany both types.
The clinical signs of chronic staphylococcal conjunctivitis include diffuse conjunctival hyperemia with papillae or follicles, minimal mucopurulent discharge, and conjunctival thickening. Erythema of the eyelid, telangiectasis, lash loss, collarettes, recurrent hordeolae, and ulcerations at the base of the cilia can be seen. The cornea may demonstrate marginal corneal ulcers ( Fig. 4.6.2 ).
Treatment combines proper antimicrobial therapy and good lid hygiene, which includes warm compresses and eyelid scrubs. Azithromycin drops and erythromycin or bacitracin ointments are effective adjunctive topical antibiotics. When severe inflammation exists, antibiotic and corticosteroid combination drops or ointments can be rubbed into the lid margins after the lid scrubs. Oral therapy with tetracycline 250 mg four times a day, doxycycline 100 mg one to two times a day, or minocycline 50 mg one to two times a day may be needed for more severe infections.
Acute Bacterial Conjunctivitis
Acute bacterial conjunctivitis usually begins unilaterally with hyperemia, irritation, tearing, mucopurulent discharge, and mattering of the lids ( Fig. 4.6.1 ). Punctate epithelial keratitis also may occur. The most common pathogens include Staphylococcus aureus , Streptococcus pneumoniae , and Haemophilus influenzae. Other common ocular manifestations include blepharitis, keratitis, marginal ulcers, and phlyctenulosis. The pathogens H. influenzae , S. pneumoniae , and Moraxella catarrhalis occur more commonly in young children and may occur in institutional epidemics. H. influenzae is often associated with systemic infection, including upper respiratory infections, and acute otitis media.
The treatment of acute bacterial conjunctivitis consists of topical antibiotic drops or ointments. Although these infections normally are self-limiting, lasting 7–10 days, antibiotic therapy usually speeds the resolution and lessens the severity of the disease. A broad-spectrum antibiotic with good Gram-positive coverage, such as a third- or fourth-generation fluoroquinolone, 10% sodium sulfacetamide, or trimethoprim-polymyxin, may be used for 7–10 days.
Hyperacute Bacterial Conjunctivitis
The most common cause of hyperacute bacterial conjunctivitis is N. gonorrhoeae. This oculogenital disease is seen primarily in neonates and sexually active young adults. Transmission is by contact with infected urine or genital secretions. Symptoms develop within 24 hours, and signs include profuse, thick, yellow-green purulent discharge, painful hyperemia, chemosis of the conjunctiva, and tender preauricular nodes. Untreated cases may lead to peripheral corneal ulceration and eventual perforation with possible endophthalmitis. A similar, but milder form of conjunctival and corneal disease is caused by primary or secondary infection with Neisseria meningitides . Primary meningococcal conjunctivitis is extremely rare in adults and can be invasive (followed by systemic meningococcal disease) or noninvasive (isolated conjunctival infection). If invasive disease is present, close contacts should receive prophylaxis with a single dose of ciprofloxacin 500 mg or rifampin 600 mg twice daily for 2 days.
Treatment is directed at the specific pathogen. Conjunctival scraping for Gram staining and culture on blood and chocolate agar are strongly recommended. Gram-negative diplococci are suggestive of Gonococcus . An effective regimen for gonococcal conjunctivitis is a single dose of 1 g of intramuscular ceftriaxone. If a corneal ulcer is present, hospitalization with 1 g intravenous ceftriaxone for 3 days is recommended. Topical medications may include bacitracin, ciprofloxacin, or erythromycin ointment every 1–2 hours. Frequent irrigation, every 30–60 minutes, with normal saline or balanced salt solution, also is recommended. Adults are often treated empirically for concurrent chlamydial infection with azithromycin 1 g once or doxycycline 100 mg twice a day for 7 days. In meningococcal conjunctivitis, systemic treatment includes intravenous penicillin, or for penicillin-resistant infections, intravenous cefotaxime or ceftriaxone. Patients need to be seen daily to rule out corneal involvement.
Chronic Bacterial Conjunctivitis
Chronic bacterial conjunctivitis, lasting longer than 3 weeks, may result from a number of organisms and is often associated with blepharitis. The most common organisms are S. aureus and Moraxella lacunata ; other causative organisms include the enteric bacteria Proteus mirabilis , Escherichia coli , Klebsiella pneumoniae , Serratia marcescens , and Branhamella catarrhalis from the upper respiratory tract. The most common causative agent is S. aureus , which colonizes the eyelid margin and then causes direct infection of the conjunctiva or conjunctival inflammation through its elaboration of exotoxins. Chronic angular blepharoconjunctivitis of the inner and outer canthal angles most commonly results from M. lacunata . A chronic follicular conjunctivitis may accompany both types.
The clinical signs of chronic staphylococcal conjunctivitis include diffuse conjunctival hyperemia with papillae or follicles, minimal mucopurulent discharge, and conjunctival thickening. Erythema of the eyelid, telangiectasis, lash loss, collarettes, recurrent hordeolae, and ulcerations at the base of the cilia can be seen. The cornea may demonstrate marginal corneal ulcers ( Fig. 4.6.2 ).
Treatment combines proper antimicrobial therapy and good lid hygiene, which includes warm compresses and eyelid scrubs. Azithromycin drops and erythromycin or bacitracin ointments are effective adjunctive topical antibiotics. When severe inflammation exists, antibiotic and corticosteroid combination drops or ointments can be rubbed into the lid margins after the lid scrubs. Oral therapy with tetracycline 250 mg four times a day, doxycycline 100 mg one to two times a day, or minocycline 50 mg one to two times a day may be needed for more severe infections.
Adenoviral Conjunctivitis
Viral conjunctivitis is extremely common. The diagnosis usually can be made clinically. Many different viruses cause conjunctivitis, and each produces a slightly different disease.
Adenoviruses produce the most common viral conjunctivitides with varying degrees of severity. The spectrum consists of follicular conjunctivitis, pharyngoconjunctival fever, and epidemic keratoconjunctivitis. These infections are spread via respiratory droplets or direct contact from fingers to the lids and conjunctival surface. The incubation period is usually 5–12 days and the clinical illness is present for 5–15 days.
Follicular Conjunctivitis
Follicular conjunctivitis is the mildest form and is associated with adenovirus serotypes 1 through 11 and 19. It has an acute onset and is initially unilateral with possible involvement of the second eye within 1 week. It is manifested by a watery discharge and conjunctival hyperemia and usually is accompanied by follicular and papillary conjunctival changes with preauricular lymphadenopathy on the affected side. Most cases resolve spontaneously, without sequelae, within days to weeks.
Pharyngoconjunctival Fever
Pharyngoconjunctival fever is the most common ocular adenoviral infection and is produced by adenovirus serotypes 3, 4, and 7. It is characterized by a combination of pharyngitis, fever, and conjunctivitis ( Fig. 4.6.3 ). The conjunctivitis is predominantly follicular with a scant watery discharge, hyperemia, and mild chemosis. The cornea may be involved with a fine punctate epitheliopathy. Preauricular lymph nodes are enlarged in about 90% of cases. The disease resolves spontaneously within 2 weeks, so treatment is usually supportive with cold compresses, artificial tears, and judicious use of vasoconstrictor eyedrops.
