Clinical Trials in Cornea

Article initiated by:

Francesc March de Ribot, MD, PhD

All authors and contributors:

Vatinee Y. Bunya, MD, MSCE, Francesc March de Ribot, MD, PhD

Assigned editor:

Neha Shaik, MD

Review:

Assigned status Update Pending

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Contributing Editors:	add

Herpetic Eye Disease Study - 1 (HEDS - 1)

Ophthalmology 1994;1871-1882 | Ophthalmology 1994;1883-1896 | Arch Ophthalmol 1996;1065-1072.

Objectives

The goal was to determine the role of 1) topical steroids in stromal keratitis associated with HSV; and 2) oral aciclovir in HSV stromal keratitis and HSV iridocyclitis (receiving treatment with topical trifluridine -antiviral- and topical steroids treatment).

Design

3 separate controlled clinical trials, randomized, double-masked, placebo-controlled to evaluate HSV 1) Stromal keratitis with steroids, 2) without steroids, and 3) Iridocyclitis. Groups:

1. SKN – Stromal keratitis, not on steroids: 106 patients who had not used a topical steroid in the preceding ten days were randomised to receive topical prednisolone or placebo. The drops over a ten-week period, commencing with 1% prednisolone phosphate 8 times a day, tapering to ⅛ once a day.
2. SKS – Stromal keratitis, on steroids: 104 patients who were already using topical steroids were randomised to receive aciclovir 400 mg five times daily for ten weeks, or placebo. Topical steroid therapy was standardised for both groups as per the SKN trial.
3. IRT – Iridocyclitis, receiving topical steroids: 50 patients who were already using topical steroids were randomised to receive aciclovir 400 mg five times daily for ten-weeks or placebo. Topical steroid and antiviral therapy were standardised for both groups.

Patients were evaluated weekly for ten weeks, fortnightly for six more weeks, and at six months.

Main outcome measures

VA, resolution of active disease, treatment failure.

Results

1. SKN – Stromal keratitis, not on steroids: 106 patients who had not used topical steroid in the preceding ten days were randomised to receive topical prednisolone or placebo. Corticosteroid therapy had a longer time to treatment failure, reduced the risk of persistent or progressive stromal keratouveitis by 68%, and had a shorter resolution time. At 6 months, there were no differences in VA or herpetic recurrence between the groups.
2. SKS – Stromal keratitis, on steroids: 104 patients who were already using topical steroids were randomised to receive aciclovir 400 mg five times daily for ten weeks, or placebo. The median time to treatment failure was longer in the acyclovir group 84 days, vs. to placebo 62 days. There were no differences in treatment failure (75% in acyclovir and 74% in placebo) or worsening (18% in acyclovir and 19% in placebo). However, VA improved over 6 months in more patients in the acyclovir group.
3. IRT – Iridocyclitis, receiving topical steroids: 50 patients using topical steroids were randomised to receive aciclovir or placebo. Oral aciclovir added to topical trifluridine and prednisolone appeared to improve the recovery in HSV iridocyclitis, after the first 3 weeks of follow-up. Treatment failure in the first ten weeks was 68% in the placebo compared to 50% in the oral aciclovir group. Relapse rates were similar between the two groups. Overall, the numbers of patients in this trial were too small to have conclusions.

Limitations

Many patients got lost in the follow-up. Modern treatment involves topical aciclovir or ganciclovir.

Conclusions

Topical corticosteroid reduced persistence or progression of stromal inflammation and HSV stromal keratitis. Postponing steroids delayed resolution of stromal keratitis but had no detrimental effect in VA at 6 months. Oral aciclovir was not useful for HSV stromal keratitis already receiving topical trifluridine and topical steroids, and it was not clear the benefits in HSV iridocyclitis.

Pearls for clinical practice

Topical steroids may speed the resolution of HSV stromal keratitis.