Long-term low-dose antiviral treatment reduces eye disease risk from shingles

Long-term, low-dose antiviral treatment reduces the risk for potentially vision-damaging bouts of inflammation and infection, as well as pain, which occur when shingles affects the eye, according to new research presented October 19 at the annual meeting of the American Academy of Ophthalmology (AAO) in Chicago.

Shingles occurs when the varicella-zoster virus, which causes chickenpox in children, lies dormant for decades in nerve cells and then starts multiplying again for reasons unknown. It commonly affects people 50 and older, and adults with impaired immune systems due to disease or treatment. The virus spreads down a nerve pathway to cause a painful blistering rash in the skin area that the nerve wires.

In about 8 percent of the more than 1 million new shingles cases in the United States each year, the virus awakens in the nerve that supplies the forehead and eye, a condition called herpes zoster ophthalmicus, or HZO. Shingles causes keratitis when it affects the cornea, and iritis when inside the eye, with both causing pain, redness, decreased vision, and sometimes glaucoma. Repeated flare-ups are associated with chronic eye disease, scarring, and vision loss.

The new research, part of the eight-year Zoster Eye Disease Study (ZEDS) and presented at the AAO meeting's Cornea Subspecialty Day, shows that study participants treated for a year with a low dose of the inexpensive and safe antiviral drug valacyclovir (Valtrex) saw a 26 percent reduction in their risk of having new or worsening eye disease (keratitis or iritis) at 18 months. Those treated were significantly less likely than those who got a placebo to have multiple disease flare-ups, with a 30 percent reduction at 12 months and a 28 percent reduction at 18 months.

In addition, participants on valacyclovir were found to have a shorter duration of pain at 18 months and needed significantly less neuropathic pain medication. Reducing the use of such medications (e.g., pregabalin and gabapentin) was a goal of the work because they have limited effectiveness and often cause dizziness, a poor fit for older patients, who are at the greatest risk for debilitating chronic pain after shingles. 

"Our results support changes in clinical practice, with suppressive valacyclovir recommended to reduce new, worsening, and repeated episodes of eye disease, as well as need for neuropathic pain medication in HZO patients and in those with shingles-related pain," said study chair and principal investigator Elisabeth J. Cohen, MD, professor of ophthalmology at NYU Grossman School of Medicine and NYU Langone Health, and vice chair for academic affairs in the department. Dr. Cohen has focused her research on HZO over the 16 years since suffering from it herself in 2008, which damaged her vision and ended her career as a cornea surgeon.

Current standard treatment is a 7- to 10-day course of an antiviral, including the study drug valacyclovir. We explored longer-term treatment because, while the standard approach has been shown to reduce the chances for chronic eye disease, it still leaves many suffering from it. We propose adding to the standard approach a year of low dose valacyclovir treatment."

Dr. Elisabeth J. Cohen, MD, professor of ophthalmology at NYU Grossman School of Medicine and NYU Langone Health

The ZEDS study was funded the National Eye Institute (NEI), part of the National Institutes of Health, and led by NYU Langone. The presentation examined whether long-term antiviral treatment could reduce eye disease and whether the same treatment lessened post-herpetic neuralgia, or PHN, the chronic nerve pain syndrome that often accompanies shingles, especially in patients over age 65.

"Up until now, there has been no proven long-term treatment for new, worsening, or repeated episodes of zoster eye disease," said ZEDS study co-chair Bennie Hau Jeng, MD, chair of the Department of Ophthalmology at the University of Pennsylvania, who also presented at the Cornea and Eye Banking Forum in Chicago. "The results of this study provide convincing evidence for using long-term, low-dose antiviral treatment to reduce eye disease in HZO and decrease pain from shingles." 

Conducted in 95 medical centers in the USA, Canada, and New Zealand, ZEDS enrolled 527 participants from November 2017 to January 2023 who were randomized to receive, double-masked, either 1,000 mg of valacyclovir daily or a placebo. Patients were required to have functioning immune systems and kidneys, be older than 18, and have had a history of typical HZO rash, and active keratitis or iritis within a year before enrollment.

"While our evidence in support of a new treatment regimen is vital, prevention is even more effective than any treatment," Dr. Cohen said. "The incidence of shingles is going up in persons in their 50s, and just 12 percent of them have received the highly effective Shingrix vaccine. This vaccine has been recommended since 2018 for all adults 50 and older and, since 2022, for immunocompromised adults 19 and older."

Other principal study investigators from NYU Langone were Andrea B. Troxel, ScD, director of the Division of Biostatistics within the Department of Population Health, and clinical trialist Judith S. Hochman, MD, the senior associate dean for clinical sciences. ZEDS was funded by NEI grant U10 EY026869 and made possible by the ZEDS network of principal investigators and study participants who volunteered. The research was also made possible through funding from the National Shingles Foundation, and a grant to the NYU Langone Department of Ophthalmology from Research to Prevent Blindness.