ZEDS (herpes zoster ophthalmicus)
Trial question
What is the role of suppressive valacyclovir treatment in patients with herpes zoster ophthalmicus?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
50.0% female
50.0% male
N = 527
527 patients (266 female, 261 male).
Inclusion criteria: adult immunocompetent, nonpregnant patients with a history of herpes zoster ophthalmicus rash, documented keratitis or iritis within 1 year.
Key exclusion criteria: immunocompromised status; renal insufficiency; allergy or adverse reaction to valacyclovir or acyclovir; history of vaccination against zoster within 1 month prior to enrolment; keratorefractive surgery; pregnancy or lactation; incarceration.
Interventions
N=266 valacyclovir (oral dose of 1,000 mg daily for 12 months).
N=261 placebo (matching placebo for 12 months).
Primary outcome
New or worsening stromal keratitis, endothelial keratitis, iritis, or dendriform epithelial keratitis at 12 months
28%
33%
33.0 %
24.8 %
16.5 %
8.3 %
0.0 %
Valacyclovir
Placebo
No significant
difference ↔
No significant difference in new or worsening stromal keratitis, endothelial keratitis, iritis, or dendriform epithelial keratitis at 12 months (28% vs. 33%; HR 0.77, 95% CI 0.56 to 1.05).
Secondary outcomes
Significant decrease in new or worsening stromal keratitis, endothelial keratitis, iritis, or dendriform epithelial keratitis at 18 months (32% vs. 40%; HR 0.73, 95% CI 0.55 to 0.97).
No significant difference in recent-onset stratum at 12 months in patients aged < 60 years (36% vs. 50%; HR 0.63, 95% CI 0.39 to 1.02).
No significant difference in recent-onset stratum at 18 months in patients aged < 60 years (41% vs. 53%; HR 0.67, 95% CI 0.42 to 1.05).
Safety outcomes
No significant difference in serious adverse events.
Conclusion
In adult immunocompetent, nonpregnant patients with a history of herpes zoster ophthalmicus rash, documented keratitis or iritis within 1 year, valacyclovir was not superior to placebo with respect to new or worsening stromal keratitis, endothelial keratitis, iritis, or dendriform epithelial keratitis at 12 months.
Reference
Elisabeth J Cohen, Andrea B Troxel, Mengling Liu et al. Low-Dose Valacyclovir in Herpes Zoster Ophthalmicus: The Zoster Eye Disease Randomized Clinical Trial. JAMA Ophthalmol. 2025 Mar 6:e246114. Online ahead of print.
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