ofherpes zoster ocular inflammation

Ninety seven new patients with ophthalmic zoster were randomly allocated to three topical treatment groups: acyclovir (ACV) ointment and placebo drops (AP), placebo ointment with steroid drops (PS), and acyclovir ointment with steroid drops (AS). The dosage administered was determined by the score ofthe ocular inflammation. Follow-up was for at least one year. The results showed that topical ACV alone is insufficient for severe ocular inflammation but is not inclined to lead to recurrences in milder cases. Topical steroid alone is effective but tends to necessitate prolonged treatment. Combined steroid and ACV is questionably better than steroid alone and causes marginally fewer rebound inflammations. Department of Clinical Ophthalmology, Moorfields Eye Hospital, City Road, London EC1V 2PD R J Marsh M Cooper Correspondence to: R J Marsh, FRCS. Accepted for publication 28 February 1991 Ophthalmic zoster has been said to give rise to ocular complications in 50% of patients.' These are chiefly inflammatory and range from being mild, such as episcleritis, to severe, such as sclerokeratitis and hypertensive iritis. The mechanisms of these complications are poorly understood but clearly involve replication of the varicella/zoster virus in the early stages and then the inflammatory response. The latter is conventionally treated with topical steroid,2 which, though usually effective, may have to be continued for long periods, as inflammation tends to reappear during or shortly after withdrawal. On the other hand, viral replication may be limited early on by acycloguanosine (acyclovir or ACV), a potent and selective inhibitor of viruses of the herpes group, in particular herpes simplex virus types 1 and 2 and to a less extent varicellazoster virus (VZV).'4 The intraocular penetration of topical ACV is superior to that of other antiviral agents5 and would therefore make it the rational choice. An open study of topical acyclovir on 18 patients with a short follow-up6 showed it controlled keratoconjunctivitis in 15 of the patients without topical steroid, and there was no recurrence on stopping treatment. A further study comparing topical ACV and steroid reported ACV to be superior to steroid in terms of the median healing time of corneal epithelial ulcers, but there was no significant difference for stromal lesions, uveitis, or scleritis.7 Of the patients on steroid 63% had a recurrence of ocular inflammation during or after withdrawal of therapy, making the mean treatment time in the steroid treated group significantly longer than in the ACV group. These results did not correspond with our experience of ACV at Moorfields,8 where half of our patients, despite being treated early with it, developed very serious ocular inflammation necessitating and responding well to topical steroids (admittedly with attendant liability to relapse). Moreover, in our experience mild disease such as corneal microdendritic ulcers, some nummular keratitis, and most cases of episcleritis are self-limiting and do not require any treatment. Therefore we consider that ACV does not have any effect in these cases and steroid could be positively harmful. The mechanisms by which rebounds in ocular disease may follow steroid withdrawal are still uncertain. Steroids can enhance viral replication9 by the suppression of some of the inflammatory responses. It is not known whether the chronic or relapsing ocular lesions in zoster are dependent on viral replication or the presence of some sort of antigen. Perhaps it is significant that, although replicating virus is present in the acute epithelial lesions of zoster,"' so far as we know replicating virus has not been identified or cultured in pathological specimens from chronic cases. It would therefore seem logical to try an antiviral during the acute phases of the disease but less certainly in the later phases. The use of ACV and steroids, separately or in combination, compared with placebo in the treatment of herpes zoster ocular inflammation has not previously been examined in a controlled clinical trial. We considered the large number of patients we see and the doubts raised by our observations justified such a three-armed double blind trial. Patients and methods New patients presenting at Moorfields Eye Hospital with ophthalmic zoster were offered inclusion in the trial. Patients excluded were those who did not give their consent, were unwilling or unable to attend regularly for clinical assessment, were under 18 years, had received antivirals or steroid by any route, had other significant ocular pathology, had no eye disease at all, and had had the onset of the rash over 3 weeks previously. Patients willing to take part were informed of the nature of the trial and gave their written consent. The trial was double masked and randomised. Patients eligible for entry were randomly allocated to receive either acyclovir ophthalmic ointment and placebo eye drops (AP), placebo ointment and steroid eye drops (PSI), or acyclovir ophthalmic ointment and steroid eye drops (AS). On admission to the trial the following details were recorded: time from onset of rash, preceding ocular therapy, other eye disease, previous glaucoma or family history of glaucoma, and whether eye involvement was mild, moderate, or severe. 542 group.bmj.com on June 22, 2017 Published by http://bjo.bmj.com/ Downloaded from