Eyeworld

SUMMER 2025 | EYEWORLD | 55 C References 1. Cohen EJ, et al. Low-dose valacyclovir in herpes zoster ophthalmicus: The zoster eye disease randomized clinical trial. JAMA Ophthalmol. 2025;143:269– 276. 2. Warner DB, et al. Low-dose valacyclovir for postherpetic neuralgia in the Zoster Eye Disease Study: A randomized clinical trial. JAMA Ophthalmol. 2025;143:277–285. Looking at post hoc analyses, Dr. Jeng said it was found that if you lumped all the recent onset patients in both age groups compared to chronic, there was a statistically significant reduction in endpoints at 1 year in the recent onset group that were treated with a P value of 0.03 and at 18 months with a P value of 0.02. "The other important secondary analysis that we found was that there was a statistically significant benefit with treatment in reducing subsequent endpoints," he said. "Just because someone had an endpoint, we didn't pull them out of the study; we kept them in their study group and continued to follow. We know that every endpoint can lead to more damage that can lead to vision loss, so we wanted to see if this treatment reduced subsequent endpoints." There was a statistically significant P value of 0.02 both at 12 and 18 months if they were treated with valacyclovir in terms of reducing subsequent endpoints. "We think the evidence supports suppres- sive valacyclovir treatment of 1,000 mg daily for 1 year to reduce these endpoints," he said. "It was statistically significant at 18 months, and the recent onset patients were more likely to benefit than chronic disease patients. The evi- dence also showed that this treatment reduces multiple endpoints." Post-herpetic neuralgia The secondary aim of the study was to look at post-herpetic neuralgia, and Dr. Jeng said this half 60 years or older, and disease manifesta- tions, especially the chronic pain syndrome of post-herpetic neuralgia, differ by the age of onset," Dr. Cohen said. "We did it by disease duration because we hypothesized that it would be more effective in people with recent onset disease, but because there are a lot of people out there with chronic disease, we didn't want to exclude them from the study." Results The primary endpoint was looking at whether there was a treatment benefit in reducing new or worsening corneal complications of stromal keratitis, endothelial keratitis, iritis, or dendri- form epithelial keratitis at 12 months, while the secondary endpoint was looking at 18 months. 1 With the first endpoint, the P value was 0.09, but the hazard ratio was 0.77, indicating a 23% reduction. At 18 months, the hazard ratio was 0.73, a 27% reduction, with a P value of 0.03. "We hit it at 18 months but missed on the primary endpoint," Dr. Jeng said. When looking at the different strata, they didn't find anything statistically significant. "We did find in one of the four strata, the less than 60-year-old recent onset disease group, the P value was 0.06, so very close. The hazard ratio was 0.63, a 37% re- duction," he said, which is clinically meaningful. The hazard ratio was only a 4% difference at 12 and 18 months, Dr. Cohen said, but that 4% was the difference between statistically significant and not. "The good news is that we showed persistent benefit after the treatment was completed," she said, adding that this is different than with herpes simplex. "That doesn't surprise me in that with herpes zoster, there is a rocky course, then it quiets down, and one figures out the lowest dose of steroid to keep a person on so that they don't flare up. But with herpes simplex, there are separate bouts of disease, separated often by years. So I think that the benefit at 18 months should determine treatment, and the data showed that the recent onset benefited more than the chronic disease." Dr. Cohen's opinion is that if there is herpes zoster affecting the eye, after the patient fin- ishes the 7–10 days of high-dose oral antiviral, they should be put on a year of low-dose valacy- clovir as soon as possible. continued on page 56 Herpes zoster stromal keratitis Source: Christopher J. Rapuano, MD

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