Getting to grips with ocular herpes

By Dermot McGrath In Bordeaux

A new arsenal of oral antiviral therapies provides ophthalmologists with enhanced options for the treatment of herpes simplex virus (HSV) keratitis as well as effective prophylaxis for patients that have already experienced the more serious stromal form of the disease, according to a French ophthalmologist.

Speaking at the Corneal 2003 meeting here, Joseph Colin MD, said that recent studies had demonstrated that long-term suppressive oral acyclovir therapy reduces the recurrence rates of both HSV epithelial keratitis and stromal keratitis.
"The severity of HSV keratitis generally increases with recurrence. In addition, the rate of recurrences after the first episode increases progressively, reaching 40% after five years. However, there is now firm evidence that antiviral treatment not only reduces the duration and severity of HSV-keratitis but also helps prevent recurrences," he said.
Dr Colin cited valacyclovir (Zelitrex,GSK) as the current anti-viral medicine of choice by virtue of its superior penetration into intraocular structures.

"If a patient takes one 500 mg tablet of valacyclovir it's the equivalent of about three tablets of acyclovir (Zovirax, GSK), which used to be the standard treatment for recurrent HSV keratitis," he said.

Dr Colin said that negotiations with the French Ministry of Health had succeeded in widening the clinical indications for valacyclovir. It can now be used in preventing recurrent HSV in cases where HSV epithelial keratitis has recurred more than three times in the space of a year from a known trigger factor.

"Before the threshold used to be six relapses in a year, so we are able to intervene much quicker now with more effective treatments than ever before," said Dr Colin.
Reviewing some of the more common pitfalls in diagnosing ocular HSV, Dr Colin said that the herpes virus was sometimes mistaken for other bacterial or parasitical infections.

"HSV is not difficult to diagnose but it is vital to distinguish it from non-viral superficial keratitis. Such a misdiagnosis poses a risk for the patient because in such cases treatment with antiviral agents will not only fail to tackle the infection but can actually make matters worse," he said.

When the eye is afflicted by herpes simplex, it usually affects only one eye and most often occurs on the cornea, said Dr Colin. In cases where the infection is superficial and limited to the epithelium, diagnosis is usually straightforward.
"Epithelial keratitis, the most common form of the virus, results in the classic lesion of a branching dendritic ulcer after staining with fluorescein. The infection lifts the edges of the epithelium, so once the fluorescein is applied to the eye, it penetrates the edges of the ulcer extremely quickly and is a very strong indicator of a viral infection," he said.

Typical symptoms include redness of the eye, soreness, photophobia, aching sensation and blurred vision depending on the site of the ulceration. Treatment using topical or oral antiviral treatment is usually straightforward and the infection normally heals in a matter of weeks without scarring.
Dr Colin said that fluorescein staining was also useful in distinguishing nonviral trophic ulcers.

"In a trophic ulcer, the epithelial cells are layered on top of one another in a distinctive structure and the cells are no longer able to attach themselves to the basal area of the ulcer. When we apply fluorescein to the eye, the ulcer is stained, but the effect is limited to the edges of the lesion and will not quickly seep under the ulceration as you would expect in cases of viral epithelial keratitis."

However, Dr Colin said that in cases where HSV has penetrated the deeper layers of the cornea, more serious complications can occur and treatment is more difficult.
"If the infection involves the deeper stromal layers, it may lead to scars of the cornea, loss of vision, and sometimes even blindness. Stromal keratitis causes the body's immune system to attack and destroy the stromal cells. Most commonly this induces a disciform oedema but a more severe inflammatory response can cause necrotising stromal keratitis."

Dr Colin noted that HSV-1 is the most common infectious cause of corneal blindness in the industrialised nations, with over 500,000 cases of ocular herpes per year in the United States alone. He said that while stromal keratitis represented only two percent of initial incidences of ocular HSV it accounted for between 20% and 48% of the more serious recurrent form of the disease.

Fungal infections, especially in patients wearing contact lenses, were another potential source of HSV misdiagnosis, according to Dr Colin.
"If your patient wears contact lenses and complains of intense pain, is suffering from redness and exhibits corneal lesions, probably unilaterally, the chances are that he is suffering from Acanthamoeba keratitis, not HSV-1. Acanthamoeba keratitis is quite common and in many instances it clears up spontaneously without the need for sustained treatment," he added.

He noted that while Acanthamoeba is slow to progress and typically takes several weeks before the infection reached the stroma, a quick diagnosis was essential to pre-empt more serious complications.

Other potential obstacles to a clear diagnosis of HSV-1 include conditions such as dystrophy of the basal membrane of the epithelium leading to recurrent keratitis, in situ epithelioma, metaplasia of epithelial cells and also bacterial infection such as streptococcus. Antiviral therapy is not indicated in such cases, he said.

Dr Joseph Colin MD
Hôpital Pellegrin-Tripode - Service d'ophtalmologie, France
joseph.colin@chu-bordeaux.fr

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