Adenoviruses are transmitted by close contact with ocular or respiratory secretions, contaminated fomites, or contaminated swimming pools. Transmission occurs more readily in populations living in close quarters, such as schools, nursing homes, military housing, and summer camps. Transmission of adenoviruses by contaminated instruments or eyedrops in physicians’ offices may also occur. For this reason, IOP measurements should be taken with an instrument that has a disposable cover.
Each subgroup (A–F) of adenoviruses and, to a lesser degree, each serotype possess unique tissue tropisms that reveal the association of specific adenoviruses with distinct clinical syndromes. Most adenoviral eye disease presents clinically as 1 of 3 classic syndromes:
simple follicular conjunctivitis (multiple serotypes)
pharyngoconjunctival fever (most commonly serotype 3 or 7)
EKC (usually serotype 8, 19, or 37, subgroup D)
The different adenoviral syndromes are indistinguishable early in infection and may be unilateral or bilateral.
Adenoviral follicular conjunctivitis is self-limited, not associated with systemic disease, and often so transient that patients do not seek care. Epithelial keratitis, if present, is mild and fleeting. Pharyngoconjunctival fever is characterized by fever, headache, pharyngitis, follicular conjunctivitis, and preauricular adenopathy. The systemic signs and symptoms may mimic those of influenza. Any associated epithelial keratitis is mild.
Epidemic keratoconjunctivitis is the only adenoviral syndrome with significant corneal involvement and may be preceded by an upper respiratory tract infection. EKC is bilateral in most patients. One week to 10 days after inoculation, severe follicular conjunctivitis develops, associated with a punctate epithelial keratitis. The conjunctival morphology is follicular but may be obscured by chemosis. Petechial conjunctival hemorrhages and, occasionally, larger subconjunctival hemorrhages can occur. Preauricular adenopathy is prominent. Pseudomembranes or true membranes (Fig 9-18) occur predominantly on the tarsal conjunctiva and may be missed on cursory examination. Patients report tearing, light sensitivity, and foreign-body sensation. Large central geographic corneal erosions can develop and may persist for several days despite patching and lubrication. Within 7–14 days after onset of ocular symptoms, multifocal subepithelial (stromal) corneal infiltrates become apparent on slit-lamp examination (Fig 9-19). Photophobia and reduced vision from adenoviral subepithelial infiltrates may persist for months to years.
Figure 9-18 Conjunctival membranes in a patient with epidemic keratoconjunctivitis (EKC).
(Courtesy of James Chodosh, MD.)
Figure 9-19 Subepithelial corneal infiltrates in a patient with EKC.
(Courtesy of Vincent P. deLuise, MD.)
Epithelial keratitis occurs because of adenovirus replication within the corneal epithelium. Subepithelial infiltrates are likely caused by an immunopathologic response to viral infection of keratocytes in the superficial corneal stroma. The evolution of keratitis in EKC is summarized in Figure 9-20. Chronic complications of conjunctival membranes include subepithelial conjunctival scarring, symblepharon formation, and dry eye due to alterations within the lacrimal glands or lacrimal ducts.
The diagnosis of EKC is suggested in the setting of bilateral follicular conjunctivitis associated with petechial conjunctival hemorrhages, conjunctival pseudomembrane or frank membrane formation, or, later in the clinical course, the presence of bilateral subepithelial infiltrates. Other adenoviral ocular syndromes have less specific signs, but laboratory diagnosis is only rarely indicated. Although viral cultures readily differentiate adenovirus from HSV infection, the clinical disease typically subsides or resolves before results become available. A rapid immunodetection assay to detect adenovirus antigens in the conjunctiva is available.
Figure 9-20 Schematic drawing illustrating the natural progression of specific corneal epithelial and stromal pathology in EKC. Stage 0, Poorly staining, minute punctate opacities within the corneal epithelium. Stage I, Fine punctate epithelial keratitis (PEK). Stage II, Fine and coarse PEK. Stains brightly with rose bengal. Stage III, Coarse granular infiltrates within deep epithelium, early subepithelial infiltrates, diminished PEK. Stage IV, Classic subepithelial infiltrates without PEK. Stage V, Punctate epithelial granularity adjacent to and distinct from the subepithelial infiltrates.
(Adapted from Jones DB, Matoba AY, Wilhelmus KR. Problem solving in corneal and external diseases. Course 626, presented at the American Academy of Ophthalmology. Atlanta, GA; 1995.)
Therapy for adenoviral ocular infection is primarily supportive. Cool compresses and artificial tears may provide symptomatic relief. Topical combination antibioticcorticosteroid drops may be indicated only when the clinical signs, such as mucopurulent discharge, suggest an associated bacterial infection or when a viral cause is less certain.
Topical corticosteroids also reduce photophobia and improve vision impaired by adenoviral subepithelial infiltrates. Because corticosteroids may prolong viral shedding from adenovirus-infected patients and can lead to worsening of HSV infections, their use should be reserved for patients with clinical signs of adenovirus infection who present with specific indications for treatment, including conjunctival membranes and reduced vision due to bilateral subepithelial infiltrates. Topical corticosteroids will produce rapid resolution of the infiltrates, but it may be difficult to wean patients from them, prolonging the course of the disease. Nonsteroidal anti-inflammatory drugs are ineffective therapy for adenoviral subepithelial infiltrates, but they may be helpful in preventing recurrence following tapering of the corticosteroids. Topical cyclosporine 1% or other immunomodulatory agents may be considered when other therapies fail.
Actively infected persons readily transmit adenoviruses. Viral shedding may persist for 10–14 days after the onset of clinical signs and symptoms. Transmission can be prevented by personal hygiene measures, including frequent hand washing; cleaning of towels, pillowcases, and handkerchiefs; and disposal of contaminated facial tissues. Individuals who work with the public, in schools, or in health care facilities in particular should consider a temporary leave of absence from work to prevent infecting others, especially those who are already ill. Patients should be considered infectious if they are still hyperemic and tearing. It is more difficult to assess transmissibility in patients treated with topical corticosteroids, who may still shed the virus even though the disease appears to be in a quiet period.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.