Therapeutic interventions for herpes simplex virus epithelial keratitis

Abstract

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

Objectives: The objective of this review was to compare the effects of various therapeutic interventions for dendritic or geographic HSV epithelial keratitis.

Search strategy: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library (Issue 3, 2007), MEDLINE (1966 to September 2007), EMBASE (1980 to September 2007), LILACS (up to September 2007), SIGLE (1980 to September 2007), ZETOC (21 September 2007), BIOSIS (up to 2005), JICT-EPlus (up to 2005), 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 included comparative clinical trials that assessed one-week 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 review author 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 included data from 99 trials that randomised a total of 5363 participants. The topical application of vidarabine, trifluridine, acyclovir or ganciclovir resulted in a high proportion of participants healing within one week of treatment. Among these 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 was not better than other antiviral agents. Interferon was very effective when combined 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 HSV 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.