TOPLINE:
Low-dose suppressive valacyclovir treatment of herpes zoster ophthalmicus (HZO) did not show significant benefits at 12 months but showed treatment superiority at 18 months and a reduction in the number of multiple episodes of keratitis or iritis at 12 and 18 months.
METHODOLOGY:
- Researchers conducted a placebo-controlled randomized clinical trial across 95 sites in the United States, Canada, and New Zealand to evaluate the efficacy and safety of suppressive valacyclovir treatment in delaying the onset of specific types of new or worsening eye diseases.
- Between September 2017 and January 2023, they enrolled 527 participants (median age, 60 years; 50.5% women) having a history of a typical HZO rash and active keratitis or iritis within the past year.
- The participants were randomly assigned to receive either 1000 mg of valacyclovir or a placebo daily for 12 months in addition to standard care, with quarterly follow-up for 18 months.
- The primary outcome was the first occurrence of new or worsening stromal keratitis, endothelial keratitis, iritis, or dendriform epithelial keratitis within 12 months.
- The secondary endpoint, evaluated at 18 months, was the persistence of treatment effects for 6 months after the treatment ended.
TAKEAWAY:
- At 12 months, new or worsening stromal keratitis, endothelial keratitis, iritis, or dendriform epithelial keratitis occurred in 33% in the placebo group compared with 28% participants in the valacyclovir group. At 18 months, they occurred in 40% vs 32% participants in the respective groups.
- At 12 months, patients receiving valacyclovir had a 23% lower risk for occurrence of new or worsening stromal keratitis, endothelial keratitis, iritis, or dendriform epithelial keratitis (adjusted 95% CI, 0.56-1.05; P = .09), although the effect was not clinically significant.
- At 18 months, patients receiving valacyclovir had a significant 27% lower risk for occurrence of any of the above-mentioned eye conditions (adjusted 95% CI, 0.55-0.97; P = .03).
- No episodes of acute kidney failure or unexpected serious adverse reactions were observed, and the percentage of participants developing serious adverse events was similar in both groups.
IN PRACTICE:
“Although significant treatment benefit of suppressive valacyclovir for HZO overall was not observed at the 12-month primary endpoint, there were secondary endpoints that supported clinically relevant benefits at 12 and 18 months,” the authors wrote.
“Given the failure of the ZEDS [Zoster Eye Disease Study] trial to demonstrate a significant benefit in the primary outcome of new or recurrent disease, it appears difficult to give a blanket recommendation for the widespread use of chronic suppressive valacyclovir therapy,” the author of an invited commentary wrote.
SOURCE:
The study was led by Elisabeth J. Cohen, MD, NYU Grossman School of Medicine, New York City. It was published online on March 6, 2025, in JAMA Ophthalmology.
LIMITATIONS:
The study had lower-than-expected enrollment, which reduced its statistical power. The study faced challenges in randomly assigning patients with HZO who were already on chronic antivirals, with the COVID-19 pandemic further affecting enrollment. Black patients, who are at a lower risk for HZO, were underrepresented. Moreover, immunocompromised patients with HZO and individuals with a low estimated glomerular filtration rate were excluded.
DISCLOSURES:
This study was supported by the National Eye Institute (NEI), the National Shingles Foundation, and Research to Prevent Blindness. Some authors reported receiving grants from the NEI and other research institutions during the conduct of the study. One author reported receiving consulting fees from an eye hospital, and another reported receiving personal fees and stock options, outside the submitted work.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.