PATHOGENESIS

Overall, 80% of cases of infectious conjunctivitis in adults are viral in origin. While, in children, the number of bacterial conjunctivitis cases is similar to that of viral conjunctivitis cases, bacterial conjunctivitis is much less common than viral conjunctivitis in adults.

Bacterial conjunctivitis is characterized by bacterial overgrowth and infiltration of the conjunctival epithelial layer and sometimes the substantia propria. The source of infection is either direct contact with an infected individual’s secretions (usually through eye–hand contact) or the spread of infection from the organisms colonizing the patient’s own nasal and sinus mucosa. In an adult with unilateral bacterial conjunctivitis, the nasolacrimal system should be examined, as nasolacrimal duct obstruction, dacryocystitis, or canaliculitis may be the underlying cause.

Though usually self-limited, bacterial conjunctivitis can occasionally be severe and sight-threatening when caused by virulent bacterial species such as N gonorrhoeae or Streptococcus pyogenes. In rare cases, it may presage life-threatening systemic disease, as with conjunctivitis caused by N meningitidis.

CLINICAL PRESENTATION

Bacterial conjunctivitis should be suspected in patients with conjunctival inflammation and a purulent discharge. The rapidity of onset and severity of conjunctival inflammation and discharge are suggestive of the possible causative organism. Table 10-3 outlines the clinical classification of bacterial conjunctivitis based on these parameters.

PATHOGENESIS

Acute purulent conjunctivitis is a self-limited infection of the conjunctiva characterized by an acute inflammatory response with purulent discharge of less than 3 weeks’ duration (definition of acute). Cases may occur spontaneously or in epidemics. The most common etiologic pathogens are S pneumoniae, Streptococcus viridans, H influenzae, and S aureus, with the relative frequency of each varying depending on patient age and geographic location.

CLINICAL PRESENTATION

Streptococcus pneumoniae conjunctivitis is characterized by a moderate purulent discharge, eyelid edema, chemosis, conjunctival hemorrhages, and occasional inflammatory membranes on the tarsal conjunctiva. Corneal ulceration occurs in rare instances.

Haemophilus influenzae conjunctivitis occurs in young children, sometimes in association with otitis media, and in adults, particularly those chronically colonized with H influenzae (eg, smokers or patients with chronic bronchopulmonary disease). Acute purulent conjunctivitis caused by H influenzae biotype III (formerly Haemophilus aegyptius) resembles that caused by S pneumoniae; however, conjunctival membranes do not develop, and peripheral corneal epithelial ulcers and stromal infiltrates occur more commonly. H influenzae preseptal cellulitis may be associated with fulminant Haemophilus meningitis, in which up to 20% of patients who recover have long-term neurologic sequelae. The incidence of infection has been reduced by a vigorous program of vaccination against Hib.

Staphylococcus aureus may produce an acute blepharoconjunctivitis. The discharge tends to be somewhat less purulent than that seen in pneumococcal conjunctivitis, and the associated signs are generally less severe.

Table 10-3 Clinical Classification of Bacterial Conjunctivitis

LABORATORY EVALUATION

Gram-stained smears and culture of the conjunctiva are usually not necessary in uncomplicated, largely self-limited cases of suspected bacterial conjunctivitis but should be used for the following:

• certain compromised hosts, such as neonates or debilitated or immunocompromised individuals, to assess the risk of local and systemic complications

• severe cases of purulent conjunctivitis, to differentiate it from hyperpurulent conjunctivitis, which generally requires systemic therapy

• cases unresponsive to initial therapy

MANAGEMENT

Most cases of acute bacterial conjunctivitis resolve in 2–7 days without treatment. Some prospective studies suggest that delaying treatment until day 3 or 4 would significantly reduce the unnecessary use of antibiotics without affecting outcomes. Initiating treatment at this time only for persistent or worsening signs would generally shorten the course and improve symptoms. If the conjunctivitis is improving on day 4, antibiotics may not be necessary at all, as these studies also indicate that initiation of antibiotics after day 4 provides limited benefit. Cases likely to represent a viral conjunctivitis should not be routinely treated with empiric antibiotics.

When the physician believes that further intervention is indicated, the initial treatment should be weighted toward the results of the Gram-stained morphology of the bacteria identified on the conjunctival smear. Definitive treatment should be based on the culture results, if available, as smear results may sometimes be inconclusive as to the predominant category of organism responsible for the infection. Cultures of the nose or throat may be obtained if an associated sinusitis or pharyngitis is present. Even if no overt sinusitis, rhinitis, or pharyngitis is present, nasal or throat swabs should be considered in cases of relapsing conjunctivitis, because organisms persisting in and colonizing the respiratory tract mucosa may be the source of infection.

Empiric therapy with polymyxin B-trimethoprim, aminoglycoside or fluoroquinolone drops, or bacitracin or ciprofloxacin ointment can be initiated before results of the Gram stain or culture have been received. The dosing schedule is 4–6 times daily for approximately 5–7 days unless otherwise indicated. Cases with gram-negative coccobacilli on Gram-stained smears are probably caused by Haemophilus species and should be treated with polymyxin B-trimethoprim. Supplemental oral antibiotics are recommended for patients with acute purulent conjunctivitis associated with pharyngitis, for those with conjunctivitis-otitis syndrome, and for children with Haemophilus conjunctivitis.

PATHOGENESIS

Gonococcal conjunctivitis presents with explosive onset and very rapid progression of severe purulent conjunctivitis: massive exudation; severe chemosis; eyelid edema; marked conjunctival hyperemia; and, in untreated cases, corneal infiltrates, melting, and perforation. The organism most commonly responsible for hyperpurulent conjunctivitis is N gonorrhoeae (Fig 10-11). Gonococcal conjunctivitis is a sexually transmitted disease resulting from direct transmission of the organism, for example, from the genitalia to the hands and then to the eyes or from the mother to the neonate during vaginal delivery.

CLINICAL PRESENTATION

Gonococcal conjunctivitis is one of the few bacterial diseases associated with preauricular lymphadenopathy and the formation of conjunctival membranes. Keratitis, the principal cause of sight-threatening complications, has been reported to occur in 15%–40% of cases. Corneal involvement may consist of diffuse epithelial haze, epithelial defects, marginal infiltrates, and ulcerative keratitis that can rapidly progress to perforation.

LABORATORY EVALUATION

Neisseria gonorrhoeae grows well on chocolate agar and Thayer-Martin media.

Figure 10-11 Peripheral corneal ulceration and perforation occurring several days after onset of hyperacute conjunctivitis caused by N gonorrhoeae.

MANAGEMENT

Gonococcal conjunctivitis requires systemic antibiotic therapy, with topical ophthalmic antibiotics used as adjunctive therapy only. Current treatment regimens for gonococcal conjunctivitis reflect the increasing prevalence of penicillin-resistant N gonorrhoeae (PRNG) in the United States. Ceftriaxone, a third-generation cephalosporin, is highly effective against PRNG. Patients with gonococcal conjunctivitis without corneal ulceration may be treated on an outpatient basis with 1 intramuscular (IM) ceftriaxone (1 g) injection; patients with corneal ulceration should be admitted to the hospital and treated with intravenous (IV) ceftriaxone (1 g IV every 12 hours) for 3 consecutive days. Patients with penicillin allergy can be given spectinomycin (2 g IM) or oral fluoroquinolones (ciprofloxacin 500 mg or ofloxacin 400 mg orally twice daily for 5 days). When possible, fluoroquinolones should be avoided in children because of potential adverse effects on joint cartilage.

Erythromycin ointment, bacitracin ointment, gentamicin ointment, and ciprofloxacin solution have been recommended for topical therapy. Treatment of severe cases should include copious, frequent (every 30–60 minutes) irrigation of the conjunctival sac with normal saline to remove inflammatory cells, proteases, and debris that may be toxic to the ocular surface and contribute to corneal melting.

Up to one-third of patients with gonococcal conjunctivitis have been reported to have concurrent chlamydial venereal disease. Because of this frequent association, it is advisable to give patients supplemental oral antibiotics for treatment of chlamydial infection. Treatment regimens for chlamydia are discussed later in this chapter. Patients should be instructed to refer their sex partners for evaluation and treatment. Other sexually transmitted pathogens causing conjunctivitis include Chlamydia trachomatis, Treponema pallidum, human immunodeficiency virus, and herpes simplex virus (Table 10-4). For further discussion of syphilis, see BCSC Section 1, Update on General Medicine, and Section 9, Uveitis and Ocular Inflammation.

American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. Conjunctivitis. San Francisco: American Academy of Ophthalmology; 2013. Available at www.aao.org/ppp.

Table 10-4 Sexually Transmitted Pathogens Associated With Conjunctivitis

Cortina MS, Tu EY. Antibiotic use in corneal and external eye infections. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2011, module 6.

PATHOGENESIS

The bacterium C trachomatis causes several different conjunctivitis syndromes; each is associated with different serotypes of C trachomatis:

• trachoma: serotypes A–C

• adult and neonatal inclusion conjunctivitis: serotypes D–K

• lymphogranuloma venereum: serotypes L1, L2, and L3

There have been reports of rare cases of keratoconjunctivitis in humans caused by Chlamydia species that typically infect animals, such as Chlamydophila psittaci (formerly Chlamydia psittaci), an agent generally associated with disease in parrots, and the feline pneumonitis agent.

LABORATORY EVALUATION

As an obligate intracellular pathogen, C trachomatis cannot be easily isolated using standard ophthalmic culture techniques, requiring either direct observation of the intracellular bacterium or cell culture. Direct visualization is possible with a Giemsa stain or direct fluorescent antibody staining. PCR probes are available and increasingly being used in place of other diagnostic methods.

CLINICAL PRESENTATION AND MANAGEMENT

Trachoma and adult inclusion conjunctivitis are discussed individually in the following sections.

CLINICAL PRESENTATION

The initial symptoms of trachoma include foreign-body sensation, redness, tearing, and mucopurulent discharge. A severe follicular reaction develops, most prominently in the superior tarsal conjunctiva, but sometimes in the superior and inferior fornices, inferior tarsal conjunctiva, semilunar fold, and limbus. In acute trachoma, follicles on the superior tarsus may be obscured by diffuse papillary hypertrophy and inflammatory cell infiltration. Large tarsal follicles in trachoma may become necrotic and eventually heal with significant scarring. Linear or stellate scarring of the superior tarsus (Arlt line) typically occurs (Fig 10-12). Involution and necrosis of follicles may result in limbal depressions known as Herbert pits (Fig 10-13). Corneal findings in trachoma include epithelial keratitis, focal and multifocal peripheral and central stromal infiltrates, and a superficial fibrovascular pannus, which is most prominent in the superior third of the cornea but may extend centrally into the visual axis (Fig 10-14).

Figure 10-12 Linear scarring of the superior tarsal conjunctiva (Arlt line, white arrows) in a patient with old trachoma with subconjunctival fibrosis (black arrow).

(Courtesy of Vincent P. deLuise, MD.)

Figure 10-13 Trachoma exhibiting Herbert pits (arrows) of the superior limbus (round to oval, pigmented areas within pannus).

(Courtesy of Tom Lietman, MD.)

Clinical diagnosis of trachoma requires at least 2 of the following clinical features:

• follicles on the upper tarsal conjunctiva

• limbal follicles and their sequelae (Herbert pits)

• typical tarsal conjunctival scarring

• vascular pannus most marked on the superior limbus

Severe conjunctival and lacrimal gland duct scarring from chronic trachoma can result in aqueous tear deficiency, tear drainage obstruction, trichiasis, and entropion.

The World Health Organization (WHO) devised a simple severity-grading system for trachoma based on the presence or absence of 5 key signs:

1. follicular conjunctival inflammation

2. diffuse conjunctival inflammation

3. tarsal conjunctival scarring

4. aberrant lashes

5. corneal opacification

The WHO grading system was developed for use by trained personnel other than ophthalmologists to assess the prevalence and severity of trachoma in population-based surveys in endemic areas.

Thylefors B, Dawson CR, Jones BR, West SK, Taylor HR. A simple system for the assessment of trachoma and its complications. Bull World Health Organ. 1987;65(4):477–483.

MANAGEMENT

Current recommendations for treatment of active trachoma are tetracycline 1% ophthalmic ointment, applied twice daily for 2 months, and oral azithromycin 1000 mg, given as a single dose. Although azithromycin is more effective and easier for patient adherence, cost and availability dictate the best therapy. Topical erythromycin, given at the same frequency as topical tetracycline, and oral tetracycline 1.5–2.0 g daily in divided doses for 3 weeks are also effective. Oral erythromycin is recommended for treatment of rare tetracycline-resistant cases. Management of the vision-threatening complications of trachoma may include tear substitutes for dry eye and eyelid surgery for entropion or trichiasis.

Figure 10-14 Superior micropannus in a patient with adult chlamydial conjunctivitis (trachoma).

CLINICAL PRESENTATION

External signs of adult inclusion conjunctivitis include a follicular conjunctival response that is most prominent in the lower palpebral conjunctiva and fornix, scant mucopurulent discharge, and palpable preauricular adenopathy. Follicles in the bulbar conjunctiva and semilunar fold are frequently present, and these are a helpful and specific sign in patients not using topical medications associated with the finding. Unlike with neonatal forms, inflammatory conjunctival membranes do not develop in adult chlamydial keratoconjunctivitis.

Corneal involvement may consist of fine or coarse epithelial infiltrates, occasionally associated with subepithelial infiltrates. The keratitis is more likely to be found in the superior cornea but may also occur centrally and resemble adenoviral keratitis. A micropannus, usually extending less than 3 mm from the superior cornea, may develop.

MANAGEMENT

Left untreated, adult chlamydial conjunctivitis often resolves spontaneously in 6–18 months. Currently, one of the following oral antibiotic regimens is recommended:

• azithromycin 1000 mg single dose

• doxycycline 100 mg twice daily for 7 days

• tetracycline 250 mg 4 times daily for 7 days

• erythromycin 500 mg 4 times daily for 7 days

Patients with laboratory-confirmed chlamydial conjunctivitis and their sexual contacts should be evaluated for coinfection with other sexually transmitted diseases, such as syphilis or gonorrhea, before antibiotic treatment is started. Sexual partners should be concomitantly treated to avoid reinfection.

Centers for Disease Control and Prevention; Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines 2006. MMWR Recomm Rep. 2006;55(RR-11):1–94.

MANAGEMENT

Because of the developing resistance of N gonorrhoeae to various antibiotics— including penicillin (PRNG), fluoroquinolones (QRNG), and tetracycline—the currently recommended first-line treatment for neonatal gonococcal conjunctivitis is ceftriaxone. For nondisseminated infections, a single IM or IV ceftriaxone injection (up to 125 mg or a dose of 25–50 mg/kg) or cefotaxime at a single dose of 100 mg/kg IV or IM is recommended. For disseminated infection, treatment should be augmented according to consultation with a specialist in infectious diseases. Either of these regimens should be combined with hourly saline irrigation of the conjunctiva until discharge is eliminated. If corneal involvement is suspected, application of topical erythromycin or gentamicin ointment or frequent application of a topical fluoroquinolone should be considered. Topical cycloplegia may also prove beneficial. Systemic treatment is advised for infants born to mothers with active gonorrhea, even in the absence of conjunctivitis.

American Academy of Pediatrics. Gonococcal infections. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. 2009 Red Book: Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:305–313.

Centers for Disease Control and Prevention; Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines 2006. MMWR Recomm Rep. 2006;55(RR-11): 1–94.

Cortina MS, Tu EY. Antibiotic use in corneal and external eye infections. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2011, module 6.