Year-Long Valacyclovir Can Alleviate Herpes Zoster Ophthalmicus

In roughly 8 percent of the more than 1 million new shingles cases in the United States every year, the reactivated varicella-zoster virus can cause herpes zoster ophthalmicus (HZO). Multiple flare-ups of the disease, in turn, can lead to scarring and vision loss. New information now shows that a readily available antiviral may offer significant relief, according to a phase 4 trial international trial led by Elisabeth J. Cohen, MD, a professor in the Department of Ophthalmology at NYU Grossman School of Medicine, where she is also vice chair for academic affairs.

Doctors commonly prescribe a 7- to 10-day course of valacyclovir to treat acute shingles symptoms, but the limited course is often insufficient to address chronic complications, particularly those affecting the eye. The new double-blind, randomized Zoster Eye Disease Study (ZEDS) showed that patients with shingles of the eye who were treated for a year with low-dose valacyclovir were 30 percent and 28 percent less likely than those receiving a placebo to have multiple disease flare-ups at 12 and 18 months, respectively. “It’s these multiple episodes that lead you to chronic disease, to chronic use of steroids, and to greater likelihood of scarring and loss of vision,” Dr. Cohen says.

The results, published in JAMA Ophthalmology, further showed that the valacyclovir-treated participants were 27 percent less likely to have new or worsening eye disease at 18 months. A second paper published the same day in JAMA Ophthalmology found that those patients on valacyclovir had less pain at 18 months and needed significantly less neuropathic pain medication.

“Our results support changes in clinical practice, with suppressive valacyclovir recommended to reduce new, worsening, and repeated episodes of eye disease,” Dr. Cohen says. “We propose adding a year of low-dose valacyclovir treatment to the standard approach for HZO patients with keratitis, iritis, or pain.” Given the effectiveness of the recombinant zoster vaccine but its low uptake, she also emphasizes the importance of increasing vaccination rates in immunocompromised adults and in everyone 50 or older.

A Potential Tool for Relieving Chronic Pain

Results of the eight-year ZEDS trial point to another “huge benefit,” Dr. Cohen says. Data from the second paper suggest that the antiviral could reduce the need for neuropathic pain medications such as pregabalin and gabapentin, which can cause significant side effects.

“The chronic pain problem, defined as lasting over three months, is especially common in people who are 65 years or older at disease onset,” Dr. Cohen explains. “You really don’t want to put older patients on medicines that make them very tired and drowsy; that’s not good for quality of life.”

Based on the ZEDS results, in fact, she suggests that low-dose valacyclovir should be further evaluated for its potential to lessen herpes zoster-associated pain in other locations around the body, given that the chronic pain syndrome after shingles is not limited to the eye.

“It’s really exciting to me because for the herpes simplex virus, ophthalmologists followed the medical doctors who are treating it,” Dr. Cohen says. “But for herpes zoster, my hope is that ophthalmologists lead the way in finding better treatment for the chronic debilitating pain and that it will be evaluated for pain due to zoster in general.”

A Productive Shift in Focus

Dr. Cohen, who served as the ZEDS study chair and principal investigator, shifted her focus from cornea surgery, keratoconus, and other infections to researching better HZO treatments after she contracted the disease herself in 2008. The condition caused her to lose much of her depth perception and central vision in her right eye.

“My first reaction was that I was a little young for this because we all think it’s something that affects older people, and I was in my fifties,” she says. But in a study conducted with colleagues at Wills Eye Hospital in Philadelphia, she reported that half of the patients with HZO were under the age of 60. 

Research in the 1990s had suggested complications of HZO weren’t only immune-mediated, as initially thought, but rather triggered by recurrent episodes of varicella zoster virus infection. Meanwhile, the Herpetic Eye Disease Study (HEDS) on eye disease related to the herpes simplex virus showed that a year of low-dose acyclovir had the unexpected benefit of reducing recurrent bouts of stromal keratitis, also thought to be immune-mediated.

“Obviously if an antiviral reduces it, a virus is triggering that inflammatory manifestation,” Dr. Cohen says. The evidence gave her the idea to test whether a similar low-dose course of valacyclovir might improve outcomes for HZO and she eventually secured funding from the National Eye Institute to set up a multicenter trial. The effort received buy-in from cornea doctors; in all, 95 medical centers in the U.S., Canada, and New Zealand participated and helped enroll 527 patients with a recent history of active keratitis or iritis.

Successfully shifting from a cornea surgeon to a clinical researcher and overcoming multiple obstacles to bring the complex study to fruition wouldn’t have been possible without the “tremendous” backing of NYU Langone, Dr. Cohen says. “An individual like me with a good idea can get great things done here because of the institutional support,” she says.