Rational acyclovir therapy in herpetic eye disease.

Abstract

SUMMARY Acyclovir has been widely used against the various manifestations of eye disease due to herpes simplex since it first became generally available in the UK nearly five years ago. This paper discusses the rational indications for its use, through considerations of its pharmacology and pharmacokinetics, and through results of the many clinical trials that have been carried out to investigate its effects since its clinical efficacy was first demonstrated in 1979. Pharmacology and pharmacokenitics of acyclovirThe antiviral effect of acyclovir (ACV) was first described by Elion et al. in 19771 and subsequently by Schaeffer et al.2 and Bauer et al.3 It was the result of a systematic search for a specific antiherpes antiviral that exploits the fact that cells replicating these viruses, and particularly herpes simplex virus (HSV), are induced by the virus to produce thymidine kinase (TK). This enzyme activates ACV to the monophosphate-the first stage in the antiviral action of the drug that gives it an overall 3000 fold greater effect against HSV replication than against host cell synthesis. ACV itself is inactive, and its lack of toxicity not only allows prolonged topical therapy if necessary, but also systemic therapy-a fact that has made dramatic improvements in the management of herpes simplex virus infections in immunocompromised patients4 and in those with herpes simplex encephalitis.5 Toxicity from topical ocular therapy with idoxuridine, trifluorothymidine, and adenine arabinoside has become widely recognised.6Topical application of ACV to the eye leads to therapeutic levels in the aqueous, even when the epithelium is intact,7 though there have been suggestions that the stromal levels from 3% ointment may be suboptimal." Oral therapy also leads to adequate levels of ACV in tears and aqueous,9 for ACV crosses the blood-aqueous barrier.It is not difficult to isolate strains of HSV that are ACV resistant: they are relatively or completely independent of TK."0 These strains are, however, of low virulence, and clinical problems with ACV resistance have been minor; but they could increase with increasing use of the drug.Correspondence to MG Falcon, FRCS.

Treatment of Herpetic Keratitis with Acyclovir: Benefits and Problems

“…The results are remarkable because any ophthalmic physician can easily treat epithelial keratitis in his surgery [11], In the IDU era. considerable skill and experience were required to treat herpetic keratitis uneventfully because a number of ocular complications could occur during the treatment.…”

Drugs used in ophthalmology—anti-infectives

“…The monophosphate derivative of vidarabine-adenine arabinoside monophosphate, otherwise known as Ara AMP-has been tested (Falcon and Jones, 1977) as an antiviral in herpetic eye disease. It was found to be better than vidarabine in inhibiting lesions but had similar effects in the treatment of established lesions.…”