This is not the most recent version of the article. View current version (9 JAN 2015)
Therapeutic interventions for herpes simplex virus epithelial keratitis
Editorial Group: Cochrane Eyes and Vision Group
Published Online: 23 JAN 2008
Assessed as up-to-date: 20 SEP 2007
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Wilhelmus K. Therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD002898. DOI: 10.1002/14651858.CD002898.pub3.
- Publication Status: Edited (no change to conclusions)
- Published Online: 23 JAN 2008
This is not the most recent version of the article. View current version (09 JAN 2015)
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.
The objective of this review was to compare the effects of various therapeutic interventions for dendritic or geographic HSV epithelial keratitis.
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.
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.
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.
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.
Plain language summary
Antiviral, interferon, and debridement treatments for herpes simplex eye disease
Herpes simplex is the most common virus acquired by humans, and ocular herpes is a prevalent and recurrent infection. Several treatments, ranging from eye medications to wiping or scraping, aim to shorten the course of herpetic eye disease when infection of the corneal surface, known as a dendrite, occurs. To examine the effectiveness of treatment options, the review author included 99 clinical trials from Europe, North America, Asia, Australia, and Africa that involved 5,363 participants who had a corneal dendrite. Healing rates at one week and two weeks were compared using different treatments, including placebo, antivirals, interferon, and ocular surface removal known as debridement. Placebo was not very effective since only 25% of corneal dendrites healed spontaneously within one week and slightly less than half by two weeks. During the 1960s, the first nucleoside antiviral drug idoxuridine (IDU) was discovered and was shown to lead to faster healing of herpetic corneal infection compared to placebo. Randomized trials subsequently found that antiviral drugs such as trifluridine and acyclovir were better than IDU; about 5 times as many patients healed within one week with trifluridine or acyclovir as with IDU. Further trials showed that trifluridine and acyclovir were equivalently effective and led to healing in two thirds of treated patients by one week and in approximately 90% by two weeks. Ganciclovir gel appeared equivalent to acyclovir ointment. Small trials with bromovinyldeoxyuridine (BVDU) or foscarnet suggested similar effectiveness as trifluridine or acyclovir. In one trial, acyclovir taken by mouth was as good as acyclovir applied to the eye. Interferon was better than placebo and as effective as other antiviral drugs. The combination of interferon-alfa eye drops and either trifluridine or acyclovir resulted in faster healing of dendritic keratitis than treatment with trifluridine or acyclovir alone; 90% of eyes healed within one week with combined interferon-antiviral therapy. Debridement by heat, chemicals, swabbing, or abrasion was commonly used before the development of antiviral drugs; the joint use of debridement and antiviral therapy seemed to speed healing and reduced recrudescent infection. Unfortunately, undue inconsistency among too few studies precluded knowing whether patients who had their infected corneal surface wiped off and then received antiviral treatment healed faster than those treated only with an antiviral medication. This review was limited by the many different therapies that have been studied and could not include 63 other trials that used inadequate methods or reported insufficient information