Stromal Keratitis in the Zoster Eye Disease Study: Lessons Learned

To report on the presentation, treatment, and visual outcome of stromal keratitis (SK) in the Zoster Eye Disease Study (ZEDS).

Secondary analysis of SK end point of randomized clinical trial.

Patients with herpes zoster ophthalmicus (HZO) were randomized in a double-masked clinical trial of oral valacyclovir 1 g daily or placebo for 1 year. They were followed prospectively every 3 months for 18 months for end points of SK, iritis (IR), endothelial keratitis (EK), or dendritiform epithelial keratitis (DEK).

Presentation of recurrent, new, or worsening SK was evaluated retrospectively by treatment assignment, randomization strata, and use of topical steroids. Investigators had been allowed discretionary treatment of end points including open-label valacyclovir and topical steroids. Visual outcome and treatment with open-label oral valacyclovir and topical steroids were evaluated.

Use of open-label valacyclovir and topical steroid treatment of recurrent, new, or worsening SK, and visual acuity at 12 months.

Recurrent, new, or worsening SK occurred in 105 of 527 participants (20%). The randomization group was not associated with this complication. Mean best-corrected visual acuity at enrollment was logMAR 0.10 ± 0.14 with no difference at 1 year, logMAR 0.13 ± 0.2, and no difference between valacyclovir and placebo groups at enrollment or at 1 year. Among the 105 instances of SK, 79 (75%) were recognized at scheduled study visits rather than at episodic visits. In only 11 of 105 (10%) of recurrent, new, or worsening SK did masked investigators opt to treat with open-label oral antiviral. At the time of SK complication, 52 of 105 participants (50%) were receiving topical steroids, but 47 of 52 participants (90%) receiving topical steroids were using 1× daily or less, 21 of 47 participants (45%) were using high potency, and 26 of 47 participants (55%) were using low potency (P = .47). Of 48 of 105 participants (47%) receiving no topical steroids at recurrent, new, or worsening SK, 18 of 48 (38%) had discontinued steroids in the prior 3 months. A total of 38 of 48 participants (75%) receiving no topical steroids at complication SK were subsequently treated with high-potency steroids 2× daily or more. Of 26 of 52 participants (50%) receiving low-potency steroids at SK complication, 23 of 26 (88%) were treated with increase in frequency only.

Individuals with ocular complications of HZO who develop SK generally maintain very good vision without the use of oral antiviral therapy when monitored closely and SK is recognized and treated. Low-potency topical steroids should be considered for treatment and ongoing suppression of SK in HZO.