Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis
Abstract
Background
Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis.
Objectives
To compare the relative effectiveness of antiviral agents, interferon, and corneal débridement in the treatment of acute HSV epithelial keratitis.
Search methods
We searched CENTRAL (The Cochrane Library 2010, Issue 4), MEDLINE (January 1950 to October 2010), EMBASE (January 1980 to October 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2010), Zetoc (British Library's Electronic Table of Contents), System for Information on Grey Literature in Europe (openSIGLE), Biosciences Information Service (BIOSIS), the metaRegister of Controlled Trials (mRCT) (www.controlled‐trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), Japan Information Center of Science and Technology (JICST‐EPlus), and China Academic Journals database (CAJ) via China National Knowledge Infrastructure (CNKI) with citations confirmed using China/Asia On Demand (COAD). There were no language or date restrictions in the search for trials. All databases except CNKI and COAD were last searched on 27 October 2010, CNKI and COAD were searched on 1 April 2010. We also searched literature digests, conference proceedings and reference lists.
Selection criteria
Of 152 eligible studies,106 comparative treatment trials involving 5872 eyes with dendritic or geographic epithelial keratitis were analysed for corneal healing over two weeks.
Data collection and analysis
Interventions were compared at 14 days after trial enrolment by calculating a risk ratio (RR) that was adjusted with indirect RR, assessed by an inconsistency index (I2 ) and supplemented by a seven‐day RR and a hazard ratio (HR).
Main results
Idoxuridine, though uncertainly better in healing outcome than control because of few trials with 14‐day follow up, allowed earlier corneal re‐epithelialisation. Vidarabine resulted in a significantly better outcome than placebo in one trial (RR 1.96; 95% CI 1.10 to 3.49). Compared to idoxuridine, in combined direct and indirect analyses, vidarabine (RR 1.11; 95% CI 1.03 to 1.19), trifluridine (RR 1.31; 95% CI 1.20 to 1.42), acyclovir (RR 1.23; 95% CI 1.16 to 1.31), brivudine (RR 1.38; 95% CI 1.18 to 1.61), and ganciclovir (RR 1.40; 95% CI 1.25 to 1.57) were significantly more effective. Trifluridine (RR 1.12; 95% CI 1.04 to 1.21) and acyclovir (RR 1.11; 95% CI 1.05 to 1.19) appeared more effective than vidarabine. No significant differences in healing were found in comparisons between acyclovir, trifluridine and brivudine. The comparison of ganciclovir to acyclovir was limited by heterogeneity and possible publication bias. The joint use of two topical antivirals (RR 1.00; 95% CI 0.89 to 1.12) and the use of oral acyclovir alone (RR 0.92; 95% CI 0.79 to 1.07) or combined with a topical antiviral (RR 1.08; 95% CI 0.99 to 1.17) appeared as effective as topical antiviral therapy. Compared to antiviral monotherapy, the combination of an antiviral with interferon (RR 1.03; 95% CI 0.99 to 1.07) or with débridement (RR 1.04; 95% CI 0.95 to 1.14) did not yield significantly better outcomes but may have accelerated healing. The corneal epithelial healing outcome was improved when antiviral therapy followed débridement (RR 1.21; 95% CI 1.04 to 1.42).
Authors' conclusions
Trifluridine and acyclovir are more effective than idoxuridine or vidarabine and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.
PICOs
Plain language summary
Antivirals, interferon, and débridement treatments for herpes simplex eye disease
Ocular herpes is a prevalent and recurrent eye infection. Without therapy, only one half of non‐complicated herpetic corneal surface infections resolve in two weeks. Several treatments, ranging from medications to superficial wiping, aim to shorten the course of herpetic infection of the corneal surface. This review provides evidence‐based guidance on the comparative effectiveness of interventions for herpes simplex virus (HSV) epithelial keratitis, by systematically analysing clinical trials from Europe, North America, Asia, Australia, and Africa. Corneal healing rates were examined during treatment with antivirals, interferon, or corneal surface débridement. The first topical nucleoside antiviral drugs, idoxuridine and vidarabine, were moderately effective but newer antiviral drugs such as trifluridine and acyclovir were better. Ophthalmic preparations of trifluridine, acyclovir, ganciclovir, and brivudine were nearly equivalently effective and allowed approximately 90% of treated eyes to heal within two weeks. In parallel with the development of nucleoside antiviral drugs, interferon, which is an antiviral protein of the immune defence system, was studied in trials that indicated effectiveness of topical formulations. Compared with antiviral treatment, the combination of interferon with a nucleoside antiviral agent seemed to facilitate early healing. Ocular allergic and toxic effects were infrequent and transitory. Before the introduction of antiviral drugs and interferon, the corneal surface was removed by physical scraping or chemical erosion, but evidence is lacking that establishes the efficacy and safety of physicochemical methods of débridement. The joint use of débridement and antiviral therapy promoted corneal recovery but was not better than single antiviral medications on corneal epithelial healing.
