Although innumerable viral entities can infect the human host, adenoviruses are the most common culprit of acute viral infection of the external eye and cornea, so it's crucial for optometrists to keep up-to-date on the latest in diagnostic and management techniques. The members of the taxonomic family Adenoviridae are medium-sized (90-100 nm) viruses containing double-stranded DNA. There have been about 50 immunologically different serotypes identified, of which half can spontaneously cause a clinical infection of the body's raucous membranes. Transmission of the disease usually occurs via hand-to-eye contact with infected secretions or by inhalation of airborne respiratory droplets.

Adenoviruses are unusually stable to adverse conditions both chemical and physical. Unfortunately, this means that they can survive for long periods outside of the body and consequently cause further spread of disease. To make matters worse, adenoviral particles are shed for two weeks after the initial appearance of symptoms, so infected patients remain contagious for this time. Clinically, adenoviral ocular infections have three basic modes of presentation: acute nonspecific follicular conjunctivitis, pharyngoconjunctival fever (PCF) and epidemic keratoconjunctivitis (EKC).

* Acute nonspecific follicular conjunctivitis. The typical clinical manifestation is a diffuse bulbar conjunctivitis along with chemosis and vascular injection. This gives the eye a very swollen appearance and a light reddish color. Thus patients often refer to this condition as "pinkeye." They report mild photophobia, incessant tearing and blurred vision in the affected eye.

When taking histories, ask the patient about a recent cold or flu. Other clinical signs of acute nonspecific viral conjunctivitis include mild lid edema, a variable follicular reaction, and palpable non-tender lymph nodes. The cornea is rarely involved. The duration can vary from several days to several weeks.

* Pharyngoconjunctival fever. PCF is an acute and highly infectious illness characterized by fever, pharyngitis, acute follicular conjunctivitis and tender, enlarged preauricular adenopathy. Usually it's seen in children and people in close quarters such as families and schools.

The incubation period after exposure to the virus is five to 12 days, at which time the patient experiences a fever lasting up to 10 days. Other associated symptoms are myalgia, malaise, and gastrointestinal disturbances. The pharyngitis is typically a reddened posterior oropharynx covered with glassy follicles with nontender cervical lymphadenopathy. Communicability is virtually 100% during the first few days and tapers to almost zero by 10 to 15 days after the onset of symptoms.

Initial patient complaints range from slight itching and burning to severe irritation and tearing but little photophobia. The lids are usually edematous within 48 hours. The conjunctivitis presents initially as a diffuse hyperemia starting in the lower fornix and extending throughout the palpebral mucosa and onto the bulbar conjunctiva. This often gives the conjunctiva a slightly gelatinous appearance. The serous discharge may result in crusting of the eyelids; in the absence of a pseudomembrane, mucopurulence is absent. Scrapings reveal a predominantly mononuclear exudate without characteristic features. The lower lid is often tender to palpation and occasionally ecchymotic. PCF is usually bilateral, with an asymmetric presentation.

A few days to one week after the onset of symptoms, the cornea will often demonstrate punctate keratitis. This begins as small epithelial dots that stain with fluorescein and progresses to combined epithelial and subepithelial focal whitish lesions, and finally to nonstaining subepithelial infiltrates. If cultures are taken, they should be taken during the acute epithelial stage because the stromal infiltrates are most likely immune complexes against residual viral antigen. The entire illness generally is acute and transient, although the subepithelial infiltrates (SEI) may last for several months. If the SEI are located near the visual axis, they may cause glare or decreased vision.

* Epidemic keratoconjunctivitis. EKC is the most severe presentation of the adenoviral conjunctivitis. The name epidemic keratoconjunctivitis refers to the extreme level of contagiosity that this virus displays. EKC presents with bilateral, inferior follicular conjunctivitis, significant hyperemia, eyelid edema and lymphadenopathy. Patients complain of tearing, photophobia and foreign body sensation.

One distinguishing feature of EKC from other adenoviral conjunctivitides is that corneal involvement is commonplace. Subepithelial infiltrates are present in most cases within the first three weeks of the disease and may persist for months. Some patients manifest a hemorrhagic conjunctivitis with papillary hypertrophy, anterior uveitis and inflammatory pseudomembrane.

EKC is more common among young adults and in the fall and winter seasons; it's unilateral in two-thirds of patients. EKC produces few to no systemic symptoms. The incubation period after exposure is about eight days, at which time there is a sudden onset of acute tearing, foreign body sensation, marked conjunctival diffuse hyperemia, follicular and papillary conjunctival response, photophobia and tender preauricular nodes.

The conjunctival involvement may become so severe that the eye develops marks of subconjunctival hemorrhaging, pseudomembranes or true membranes, or symblepharon formation that may scar the lid to the globe. In four out of five patients, the pain and discomfort worsens, usually coinciding with the development of keratitis around the eighth day. This is heralded by marked discomfort, photophobia, lacrimation and blepharospasm.

The keratitic disease commonly is divided into four stages:

* Stage 1 involves diffuse, fine, superficial epithelial punctate keratitis due to the live virus.

* Stage 2 occurs quickly thereafter, and features a coalescence of these lesions to focal white punctate epithelial lesions that stain with fluorescein.

* Stage 3 occurs within 24 to 48 hours, when these areas become combined epithelial and subepithelial areas.

* Stage 4 occurs days later when the subepithelial white macular lesions no longer stain with fluorescein. Occasionally, lesions coalesce to form scallopedged nummular opacities that may mimic herpes simplex viral keratitis.

These symptoms persist until the acute epithelial phase subsides, usually within two or three weeks. By this time, the conjunctivitis also resolves. The subepithelial corneal infiltrates may persist for months in some patients, causing a decrease in vision as well as photophobia.

Pinpoint the problem

Diagnostic techniques for adenovirus include cytologie scrapings that reveal a mixed lymphocytic and polymorphonuclear leukocyte infiltrate and degenerated epithelial cells without inclusion bodies. Viral cultures are positive 82% of the time if taken in the early course of the disease. Alternative diagnostic techniques include paired blood specimens, with the first drawn within seven days of the onset of symptoms and the second drawn two to three weeks later. A four-fold increase in humoral antibody to adenovirus indicates a recent infection.

Clinically, the diagnosis is usually made on the basis of slit lamp examination and patient symptoms.

What are your options?

Because EKC and PCF are contagious and self-limiting, the primary treatment is educating patients about transmission to others. Even so, something must be done for severe presentations which often result in significant patient discomfort and ocular compromise. Unfortunately, the human adenoviruses do not respond to antiviral agents such as vidarabine and trifluridine. Cold compresses, ocular lubricants, and topical non-steroidal anti-inflammatory agents are helpful during the acute phase of the disease. Steroid use is controversial.

In EKC, topical corticosteroids help reduce lymphocytic infiltration and hasten the recovery of vision and comfort secondary to corneal SEI. However, steroids have no beneficial therapeutic effect on the ultimate clinical outcome. Studies show that the subepithelial infiltrates recur when steroids are discontinued and that only time ultimately resolves their presence.

Additionally, more recent studies show that topical steroids reduce conjunctivitis and subepithelial infiltrates and increase viral replication and duration of viral shedding in the adenovirus type 5 rabbit ocular model. If this is true, it means that steroids actually prolong the time a patient is contagious.

You should remove pseudomembranes, which consist of coagulated exudate that's loosely adherent to the inflamed conjunctiva. Do this at the slit lamp using a moistened cotton-tipped applicator or forceps.

Waiting in the wings

Two new forms of therapy have received attention recently. Cidofovir (Vistide, Gilead Sciences), an antiviral drug used intravenously to treat cytomegalovirus retinitis, appears effective against some types of adenoviral keratoconjunctivitis. Used twice a day, this topical anti-viral is currently awaiting Food and Drug Administration approval in the United States.

Another therapeutic consideration that's been investigated recently is the application of povidone-iodine, a well-known antiseptic agent, directly to the conjunctiva. This treatment modality has also yet to be approved by the FDA.

Parting pearls

With any suspected case of viral conjunctivitis, keep your equipment, instruments and chair area meticulously clean to avoid contaminating your patients and staff. Doctors and technicians should take care to properly wash hands between patient visits. Additionally:

* Advise infected patients to avoid close personal contact for at least two weeks and to use their own towels, wash cloths, and pillows. They should also wash bed linens regularly during the course of the disease

* Reserve steroid use for severe cases. Even then, try a course of topical NSAIDs first because EKC infiltrates usually resolve spontaneously without scarring the cornea. If you do prescribe steroids, slowly taper them as the condition resolves and monitor IOP.

* Educate your patients that the symptoms will get worse for the first week before getting better, and that it may take a month or longer for total resolution. Doing so will save you phone calls from alarmed patients.

DEEPAK GUPTA, O.D., F.A.A.O.

Stamford, Conn.

Dr. Gupta practices full-scope primary care optometry at Stamford Ophthalmology. You can reach him at deegup4919@hotmail.com.

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