Eyeworld

54 | EYEWORLD | SUMMER 2025 C ORNEA CHANGING MINDSETS by Ellen Stodola Editorial Co-Director About the physicians Elisabeth Cohen, MD Professor and Vice Chair for Education, Faculty, and Academic Affairs Department of Ophthalmology NYU Grossman School of Medicine NYU Langone Health New York, New York Bennie H. Jeng, MD William F. Norris and George E. de Schweinitz Professor Chair, Department of Ophthalmology Director, Scheie Eye Institute University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania R esults from the Zoster Eye Disease Study (ZEDS) were first presented last year. This randomized clinical trial was conducted in 95 sites from November 2017 to June 2024, looking at the use of low dose valacyclovir for reducing complications with herpes zoster ophthalmicus (HZO). Elisabeth Cohen, MD, and Bennie H. Jeng, MD, spoke to EyeWorld about the results, highlighting recently published papers on find- ings from the study. Since the 90s, we've learned that com- plications of zoster are associated with active varicella zoster virus infection, Dr. Cohen said. She noted the Herpetic Eye Disease Study, which looked at herpes simplex virus eye dis- ease, showed that low-dose, prolonged acyclovir was effective in reducing recurrent episodes of disease during the 12 months that patients were on it but not during the 6 months after they stopped taking the low-dose acyclovir. "In about 2010, I had the idea to try treating zoster the way we treat herpes simplex eye disease," she said. "I had zoster in my eye in 2008 and had a bumpy course, and after a year, I had lost vision to the point that I had to give up being a regular cornea doctor, seeing patients, because I didn't have the depth per- ception to do microsurgery anymore. I was very well taken care of, and every time I got worse, they gave me another week of high-dose antivi- ral treatment. Then I had this light bulb go off and thought, 'Why don't we do prolonged low- dose treatment for HZO like we do for HSV?'" Zoster Eye Disease Study (ZEDS) Dr. Cohen began the undertaking of writing the grant for what would become the Zoster Eye Disease Study (ZEDS), which was submitted in September 2013 with 60 U.S. centers agreeing to participate. It took three tries before it was finally funded by the National Eye Institute of the National Institutes of Health in 2016, Dr. Cohen said, adding that a lot of cornea doctors who were going to be involved with the study started using the treatment, despite a lack of good evidence to support its use. The concept was to enroll HZO patients who had involvement in their eye within the year prior to enrollment. They could have a history of a typical rash any time in the past, but they needed to have active keratitis or iritis within 1 year of entering the study. Dr. Jeng noted that the study was conduct- ed in 95 centers across the world, mostly in the U.S. but also in Canada and New Zealand. There were 527 patients enrolled, and they were randomized to 1,000 milligrams per day of valacyclovir double masked versus placebo for 1 year of treatment and 18 months of follow-up. "It is important to note, even at the outset of the study in the statistical analysis plan, we identified four different strata that patients would be randomized into," Dr. Jeng said. These strata were by age—with cutoffs of younger than 60 years or 60 years and older— and time since onset of disease at enrollment— less than 6 months or greater than 6 months— to define recent onset versus chronic disease. The purpose of that was that it was expected for disease manifestations to vary by age. "We also expected a greater benefit of treatment in the recent onset group," he said. He noted that 460 completed the 18-month study, which included 1 year of treatment of either drug or placebo and 6 months of follow-up when patients were off the treatment. "We did it by age because we thought half of the people would be under 60 years and Highlighting results from the Zoster Eye Disease Study (ZEDS) Herpes zoster dendriform epithelial keratitis Source: Christopher J. Rapuano, MD

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