Oral antivirals offer convenience, efficacy to those with acute infections

January 1, 2007

Las Vegas-Herpes simplex virus (HSV) keratitis is the leading infectious cause of corneal blindness in the developed world, said Deborah Pavan-Langston, MD, FACS, at the American Academy of Ophthalmology annual meeting. HSV infection also is one of the most complicated illnesses, because it encompasses mechanical and immune as well as infectious components, continued Dr. Pavan-Langston, associate professor of ophthalmology, Harvard Medical School, Boston.

But oral antiviral medications offer effective new ways to treat acute herpetic infections and provide long-term prophylaxis against recurrent stromal immune disease and infection in postherpetic keratoplasty, she said.

The dosing schedules for oral antiviral medications used to treat acute epithelial infectious ulcers are much more convenient than those for topical antiviral therapy, she said, increasing the likelihood of therapy adherence.

At 14 days, about 95% of the ulcers will be healed, she said, but in addition to compliance issues associated with the fact that the medication must be taken frequently, "there's also a notable chance of toxicity in the form of conjunctivitis, punctate keratitis, punctal occlusion, or contact dermatitis."

Alternatively, she said, oral antiviral medications can treat acute infections with fewer doses in 14 to 21 days. The options include acyclovir (Zovirax, GlaxoSmith-Kline Inc.), famciclovir (Famvir, Novartis Pharmaceuticals Corp.), and valacyclovir (Valtrex, GlaxoSmithKline Inc.).

"Acyclovir is given in doses of 400 mg three to five times a day, with the five-times-a-day dose generally used in patients who are atopic or otherwise immuno-altered," explained Dr. Pavan-Langston, also a surgeon and director, clinical virology, Massachusetts Eye and Ear Infirmary. The pediatric suspension of the drug is given in doses of 200 mg per teaspoon, or 5 ml, four times a day, she said.

Famciclovir is prescribed in doses of 125 to 250 mg twice daily, and valacyclovir dosing is 500 mg twice daily, Dr. Pavan-Langston said.

Long-term prophylaxis

A secondary use for antiviral medications is long-term prophylaxis against recurrent stromal immune disease and infection in postherpetic keratoplasty, Dr. Pavan-Langston said, and the doses are lower than those used to treat acute infections. Dosing for acyclovir, for instance, is 400 mg twice a day for 1 to 6 years or more.

"We have patients who have been [taking] it 9 years or more with no problem," she said. Famcicolvir can be given 125 to 250 mg once or twice daily for a year or somewhat longer, she added, and valacyclovir is prescribed at 500 mg once or twice daily for a year.

In periocular dermal infection with no ocular involvement, skin vesicles are infectious for 3 to 6 days, and prophylactic therapy lasts 7 to 10 days to protect the eye.

"You use full-dose antiviral pills or suspension or trifluridine drops, and within a matter of days you'll get scabbing over and, ultimately, healing without scarring," Dr. Pavan-Langston said.

Infectious corneal epithelial HSV pre-sents with dendrite, dendrogeographic, or geographic ulcers caused by mature virus, she said. Therapy with oral antiviral medication or trifluridine drops lasts 14 to 21 days. Poor healing, however, may be evidence of herpetic neurotrophic keratopathy, Dr. Pavan-Langston said.

"This is from neural damage to the cornea, which results in neuropeptide and neurotransmitter loss, hypesthesia or anesthesia, and dry eye," she said. "That, in turn, will lead to poor ocular surface health and healing ability, and that may go on to cause a sterile neurotrophic ulcer."

Consider progression