Mitigating HZO

In the US, around one in three people will contract shingles (herpes zoster) during their lifetime, with this likelihood increasing as they get older and their immune systems grow weaker. Shingles in the eye – or herpes zoster ophthalmicus (HZO) – is a variation of herpes zoster that, if left untreated, can cause potentially sight-threatening damage through ocular manifestations including uveitis, keratitis, and conjunctivitis.

New findings from the Zoster Eye Disease Study (ZEDS), presented at the American Academy of Ophthalmology (AAO) 2024 meeting in Chicago, have revealed that a long-term, low-dose antiviral treatment could reduce the risk of inflammation, infection, and ocular pain caused when shingles affects the eye.

Study chair and Professor of Ophthalmology at NYU Grossman School of Medicine, Elisabeth Cohen, explains, “ZEDS showed 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.”

Cohen has personal experience with the disease, having contracted HZO in 2008, which damaged her vision and put an untimely end to her career as a successful cornea surgeon. “Well before I suffered from HZO, I was always interested in infectious diseases,” says Cohen. “In the ‘90s, I was a regional principal investigator for the Herpetic Eye Disease Study (HEDS), which showed that a year of low-dose antiviral medication reduced episodes of herpes simplex virus disease in the eye. So when HZO damaged my vision, I had the idea to try treating herpes zoster the same way.”

Conducted in 95 medical centers across the US, Canada, and New Zealand, the study enrolled 527 participants from November 2017 to January 2023. The participants were randomized to receive either a placebo or 1000 mg of valacyclovir. “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,” says Cohen. “In addition, participants on valacyclovir were found to have a shorter duration of pain at 18 months and needed significantly less neuropathic pain medication.”

The study results support changes in clinical practice, with the researchers recommending suppressive valacyclovir be used to reduce new, worsening, and repeated episodes of eye disease. “Current standard treatment is a seven- to 10-day course of an antiviral, including the study drug valacyclovir,” Cohen explains. “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.” Cohen adds, “I would recommend ophthalmologists put HZO patients with keratitis or iritis on one year of low dose suppressive valacyclovir, as soon as possible.”

In terms of next steps, the team is currently “analyzing the data with regard to participants who were vaccinated with recombinant zoster vaccine to prevent shingles, to see if this triggered endpoints or not, and whether it was mitigated by the use of suppressive valacyclovir.” The team is also evaluating patient compliance in taking the treatment, to gain further insight into the optimal duration and dose for the patient.

While Cohen believes ZEDS conclusively supports this long-term treatment regimen, she also says that, as with many other ocular diseases, prevention is more effective than treatment. “The incidence of shingles is going up in persons in their 50s, and only 12 percent of them have received the highly effective Shingrix vaccine,” she adds. “This vaccine has been recommended since 2018 for all adults 50 and older and, since 2022, for immunocompromised adults 19 and older.”

Information about the study:
 

The ZEDS study co-chair was Bennie Hau Jeng, chair of the Department of Ophthalmology at the University of Pennsylvania. Other principal study investigators from NYU Langone were Andrea B. Troxel, director of the Division of Biostatistics within the Department of Population Health, and clinical trialist Judith S. Hochman, the senior associate dean for clinical sciences. The ZEDS study was funded by a grant from the National Eye Institute (NEI), part of the National Institutes of Health, and was 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.