Interventions for herpes simplex virus epithelial keratitis

  • Review
  • Intervention


  • KR Wilhelmus

Kirk Wilhelmus, Professor of Ophthalmology, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, 6565 Fannin Street, NC-205, Suite NC-304, Houston, TX, 77030, USA.



Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus eye disease have evaluated different interventions, but a systematic review of all comparative clinical studies has not previously been undertaken.


The objective of this review is to compare the effects of various treatments for dendritic or geographic herpes simplex virus epithelial keratitis.

Search strategy

Sources searched for relevant studies were the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group trials register), (Issue 3 2002) , MEDLINE (1966 to August 2002), EMBASE (1980 to August 2002), LILACS (up to 2002), Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960 to 1973), reference lists of primary reports and review articles, and conference proceedings pertaining to ocular virology.

Selection criteria

This review includes comparative clinical trials that assessed one-week and/or two-week healing rates of topical ophthalmic or oral antiviral agents and/or physical or chemical debridement in people with active epithelial keratitis.

Data collection and analysis

The reviewer extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrolment.

Main results

This review includes data from 97 trials that randomised a total of 5102 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir generally resulted in a significantly greater proportion of participants healing within one week of treatment. Among these three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical or physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis, but not better than other antiviral agents, although interferon was very useful combined with debridement or with another antiviral agent such as trifluridine.

Authors' conclusions

Currently available antiviral agents are effective and nearly equivalent. The combination of a nucleoside antiviral with either debridement or with interferon seems to speed healing. Future trials of the acute treatment of herpes simplex virus epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome of epithelial healing and should consider the effect of lesion size and other characteristics on treatment response.

Plain language summary

Plain language summary

Most antiviral agents are effective in healing ulcers on the eye caused by herpes simplex keratitis

Herpes simplex virus epithelial keratitis is a condition in which infectious ulceration forms on the surface of the eye. Several different types of treatment are available for herpetic keratitis including many antiviral drugs. This review found that currently available drugs are generally similar in their effectiveness in helping the corneal surface to heal and are better than older methods of wiping the ulcer off the eye.