Oral antivirals: A prominent role in many ocular manifestations of herpes

Issue: September 2006

ByJennifer Byrne

Oral antivirals play an important role in the treatment of ocular herpetic infections, both in terms of decreasing recurrence rates and reducing the duration of post-herpetic neuralgia.

Christopher Quinn, OD, FAAO [photo]
Christopher Quinn

The current lineup of oral antivirals, such as acyclovir, famciclovir and valacyclovir, continue to effectively fight the herpes virus, said Christopher Quinn, OD, FAAO, a Primary Care Optometry News Editorial Board member who practices at Omni Eye Services, Iselin, N.J. However, a need for emerging treatments continues to exist, he said.

“Everyone appreciates something newer and better,” he told PCON in an interview. “Resistance to oral antivirals is unusual, but it certainly does occur. Obviously, anything in the pipeline would be good, not just for herpetic infections, but also for adenoviral infections.”

Prompt therapy imperative with zoster

In cases of herpes zoster, Dr. Quinn said one of the primary roles of oral antivirals is to decrease the duration of post-herpetic neuralgia.

“Prompt initiation of oral therapy within 3 days of the outbreak of the skin lesions in herpes zoster can result in a significant reduction in the duration of post-herpetic neuralgia, which is probably the most debilitating complication associated with the herpes zoster infection,” he said. “So it is very important, obviously, that patients who are diagnosed with zoster ophthalmicus be started on antiviral agents.”

Gary E. Oliver, OD, FAAO [photo]
Gary E. Oliver

According to Gary E. Oliver, OD, FAAO, associate clinical professor for SUNY State College of Optometry and a private practitioner, oral antivirals are absolutely necessary for the treatment of herpes zoster infections, because of the reactivation of the latent varicella virus along the affected nerve.

“Herpes zoster ophthalmicus is an immune reaction in conjunction with the active dermatological infection,” he said in an interview. “For best results, treatment of herpes zoster reactions should begin within 72 hours of symptoms.”

However, Dr. Oliver said, therapy should not be withheld if the patient comes in with a longer time of onset. “Acyclovir 800 mg five times a day or famciclovir 500 mg three times daily for 7 to 10 days would be the treatment of choice,” he said.

Dr. Oliver said the most common ocular reactions in herpes zoster ophthalmicus are conjunctivitis and anterior uveitis. “The conjunctivitis can be treated with topical steroids such as 1% prednisolone acetate or 0.5% loteprednol,” he said. “The uveitis is best treated with 1% prednisolone acetate.”

Herpes simplex treatment, stromal keratitis

For herpes simplex, the situation is slightly more complicated, Dr. Quinn said. “The oral antiviral agents have been proven to reduce recurrence rates of stromal herpes keratitis,” he said. “So patients with stromal keratitis should be treated with oral antivirals for 1 year. This cuts the rate of recurrence almost in half.”

In cases of herpes epithelial keratitis, oral antiviral agents do not prevent patients from developing stromal keratitis, Dr. Quinn said. However, he added that oral agents may effectively treat epithelial disease if patients have experienced toxicity related to topical antivirals.

“There certainly was hope that the prompt use of oral antivirals would prevent those with epithelial herpes keratitis from going on to develop stromal herpes keratitis,” Dr. Quinn said. “But that has not turned out to be the case. So there is more of a limited role for oral agents in epithelial disease than for stromal disease.”

Dr. Quinn said it could be argued that there has never been a carefully conducted clinical trial to examine the efficacy of oral antivirals in reducing recurrence rates of epithelial disease.

“With herpes simplex, you really see the benefit of oral antivirals in terms of reduced recurrence rates,” he said.

Dr. Oliver added that clinical trials have shown that the recurrence rate of herpes simplex infections in some patients may be lowered with a maintenance dose of oral acyclovir 400 mg, twice a day for 1 to 2 years following a recurrent episode. Some practitioners also prescribe valacyclovir 500 mg once a day, he added. “Patient compliance is obviously an issue with this type of long-term therapy,” he said.

Topical antivirals for herpes simplex

HSV dendritic keratitis: Both topical and oral antivirals are important elements of ocular herpes treatment.

Most ocular herpes simplex infections typically respond well to treatment with the topical Viroptic (1% trifluridine solution, Monarch) because of its ability to achieve high therapeutic titers on the surface of the eye and within the cornea, according to Dr. Oliver.

“This is due to its ability to completely penetrate the cornea,” he said. “Oral antiviral agents are useful in cases of herpetic dermatitis, keratouveitis, uveitis, posterior stromal keratitis and in cases where patients are intolerant to eye drops or trifluridine solution.”

Dr. Oliver said patients with long histories of recurrent disease or presentations of multisite disease, such as dermatitis and conjunctivitis, may also do better with oral antiviral therapy.

“Herpes simplex responds well to any of the three oral antiviral agents — acyclovir, valacyclovir or famciclovir,” he said. “The typical dosages for these agents for herpes simplex infections are acyclovir 400 mg five times a day, valacyclovir 500 mg three times daily or famciclovir 500 mg twice daily for 1 week.” This is a lower dosing frequency and duration than is recommended for herpes zoster treatment.

He said the use of concurrent 1% trifluridine solution with an oral antiviral agent is typically not necessary, due to the fact that the therapeutic titers of the oral agents are achieved in the tear film and external eye within 72 hours of starting therapy.

Dr. Oliver said it is common for practitioners to reach for valacyclovir for herpes simplex and famciclovir for herpes zoster.

“When prescribing oral antiviral agents, many practitioners prefer valacyclovir for herpes simplex and famciclovir for herpes zoster, primarily due to the lower frequency of dosing, which increases patient compliance,” he said. “In cases of herpes zoster, clinical studies have shown that famciclovir may be slightly more effective.”

For more information:

Christopher Quinn, OD, FAAO, is a member of the Primary Care Optometry News Editorial Board. He can be reached at Omni Eye Services, 485 Route 1, Iselin, NJ 08830-3009; (732) 750-0400; fax: (732) 750-1507; e-mail: cqod@comcast.net.

Gary E. Oliver, OD, FAAO, is an associate clinical professor for the SUNY State College of Optometry and a private practitioner. He can be reached at 946 Hunt Drive, Yardley, PA 19067; (215) 796-0455; e-mail: geoliver.od@att.net.