Q: I recently sent a patient with a central herpes simplex dendrite to an ophthalmologist for a second opinion. I had started the patient on Viroptic, but the report that I got back said “topical drops are no longer used for this,” and that the patient needs oral acyclovir. Am I missing something?

A “The answer is still up in the air,” says Jimmy Lee, M.D., director of the cornea and refractive surgery sections and assistant professor of ophthalmology and visual science at Yale Eye Center, New Haven, Conn. “Part of the reason is that we don’t have a consensus.”

The type of treatment depends upon whether it is the first presentation (i.e., acute) or a recurrent epithelial dendritic keratitis, says Dr. Lee. “If it’s a first acute episode, then one could argue that you don’t need oral antivirals, and that treating them with topical medication is OK,” he says.

The mainstay of topical antiviral treatment has been Viroptic (trifluridine, Monarch Pharmaceuticals). “But topical Viroptic can be very toxic to the epithelium. Patients find it very irritating, so compliance has always been an issue,” Dr. Lee says. Also, it’s dosed every two hours up to nine times a day. Add this onerous regimen to its toxic effect, “and compliance at that full dosing is questionable.”

That’s why some clinicians have instead adopted an “orals only” approach, in which patients with acute herpes simplex are given oral antivirals instead of topical therapy.1

Is oral acyclovir the answer for an acute herpes simplex dendrite?
While the “orals only” approach is still a matter of debate, “there’s lot of good data on oral acyclovir now,” Dr. Lee says. He points to a newly published study that investigated the effect of oral antiviral prophylaxis for herpes simplex eye disease in a single community over the course of 30 years.2

“For patients who had acute herpetic keratitis, about half of them were placed on oral antivirals and half were told to just go home,” he says. “The ones given oral antivirals were more than nine times—not double or triple, but nine times—less likely to get recurrent epithelial keratitis. That’s a very strong argument for the prophylactic use of oral acyclovir.”

Another argument for the “orals only” approach (even in acute cases): it’s inexpensive. If the patient can’t afford a topical antiviral, then prescribe generic acyclovir 400mg five times a day to treat any dendrite, whether it’s the first presentation or a recurrence.

Some clinicians adopted the “orals only” approach in response to the toxic effects of Viroptic. Now, with the recent approval of the topical antiviral Zirgan (ganciclovir, Bausch + Lomb) patients have a therapy that is more comfortable, Dr. Lee says.

Also, “it comes in a gel form so it lingers around a little longer on the corneal surface,” he says. “And, the dosing is five times a day, so it’s less frequent [than Viroptic].” Also, Zirgan doesn’t have the systemic side effects of oral ganciclovir. “So, for me personally, it’s my first-line choice when the patient has acute herpes simplex epithelial keratitis.”

For patients with this presentation, that’s usually all he’ll prescribe. “I don’t necessarily put everyone on oral acyclovir for the first episode. I’ll put them on Zirgan and if they do well, fine. If they have a recurrence, that buys them an oral antiviral,” Dr. Lee says. “If the patient has multiple episodes—two or three times a year—I’ll strongly insist that we put them on oral prophylaxis.”

If your patient has a more involved presentation, such as stromal disease or a large dendrite on the visual axis, be sure to get a second opinion from a corneal specialist. Some surgeons (including Dr. Lee) opt to debride a large, centrally located dendrite before beginning medical therapy.

1. Collum LM, McGettrick P, Akhtar J, et al. Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration. Br J Ophthalmol. 1986 Jun;70(6):435-8.
2. Young RC, Hodge DO, Liesegang TJ, Baratz KH. Incidence, recurrence, and outcomes of herpes simplex virus eye disease in Olmsted County, Minnesota, 1976-2007: the effect of oral antiviral prophylaxis. Arch Ophthalmol. 2010 Sep;128(9):1178-83.