The potential benefit of suppressive valacyclovir varied across the 18-month ZEDS follow-up, with protective effects concentrated during early treatment and the observation period after therapy ended. Photo: Harriette Canellos, OD. Click image to enlarge.
A year of suppressive valacyclovir may help reduce subsequent episodes of keratitis and iritis in patients with herpes zoster ophthalmicus (HZO), although the magnitude of benefit may vary over time. A post hoc analysis of the Zoster Eye Disease Study (ZEDS), published recently in JAMA Ophthalmology, found potential protective effects during the first six months of treatment and again during the six months after therapy ended.
The original multicenter ZEDS trial randomized 527 immunocompetent, nonpregnant adults with a history of HZO and active keratitis or iritis within the previous year to daily valacyclovir 1,000mg or placebo for 12 months, followed by six months of observation. The primary outcome included new or worsening stromal keratitis, endothelial keratitis, iritis or dendriform epithelial keratitis.
In the new exploratory analysis, researchers examined whether the effects of prophylaxis varied across the 18-month study period. Valacyclovir was associated with a lower likelihood of new or worsening ocular disease during the first six months of therapy, while little difference between treatment groups was observed from six to 12 months. A potential protective effect emerged again during the six-month observation period after treatment ended.
None of the time-specific comparisons reached statistical significance. The researchers also emphasized that the original ZEDS primary outcome did not demonstrate a significant benefit of suppressive valacyclovir. However, previously reported secondary outcomes favored treatment at 18 months and showed fewer multiple episodes of keratitis or iritis at both 12 and 18 months.
This research provides additional support for considering a one-year course of prophylaxis following HZO-associated keratitis or iritis. The authors cautioned that the analysis was exploratory and suggested treatment decisions should account for an individual patient’s risk of disease relapse, medication tolerability and kidney function.
“The findings of this post hoc exploratory analysis of the ZEDS randomized clinical trial suggest prophylactic valacyclovir treatment for a period of 12 months might be considered after the diagnosis of HZO with keratitis or iritis to reduce disease morbidity,” the study authors concluded. They added that, in the absence of another prospective trial evaluating a different duration of prophylaxis, ZEDS can help guide management in patients who meet the study criteria.
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