Double-Blind Clinical Trial of Acyclovir and

Adenine Arabinoside in Herpetic Cornea1 Ulceration

BRENDAN YOUNG, M.B., F.R.C.S.

A. PATTERSON, M.D., F.R.C.S.

Liverpool, United Kingdom

T. RAVENSCROFT

Becker&m, United Kingdom

From the St. Paul’s Eye Hospital, Liverpool, United Kingdom, and Wellcome Research Laboratories, Beckenham, Kent, United Kingdom. Requests for reprints should be addressed to Dr. Brendan Young, St. Paul’s Eye Hospital, Old Hall Street, Liverpool, United Kingdom.

The resuits of a double-blind clinical trial of acyclovir and adenostne arabinoside (ara-A) in 93 patients with herpetic keratftis demon- strated a significantly faster healing rate for acyciovir (p <O.Ol). Ulcers in 45 (94 percent) of acyciovir-treated patients and 37 (82 percent) of ara-A-treated patients healed within 14 days. No serious side effects were observed.

METHODS AND PATIENTS

Patients with clinical diagnosis of herpetic cornea1 ulceration based on slit- lamp biomicroscopy were included in the study. Patients who were aged 16 years or younger, who were of childbearing potential, who had a visual acuity of 6124 or worse in the contralateral eye, who had received other antiviral therapy for the current episode, or who were unable to attend for follow-up were excluded.

Full ocular examinations were performed by one of two ophthalmologists; when possible each patient was seen by the same person. Patients were seen on alternate days during the first 10 days of the study, then twice weekly. Treatment with 3 percent acyclovir” or 3 percent adenine arabinoside (ara-A) was assigned randomly to patients in identical tubes. Ulcers that failed to heal within 14 days, remained static for seven days, or worsened over three days were crossed over, under the direction of the Chief Pharmacist, to the al- ternative medication.

Patients receiving steroids at presentation and those with ameboid ul- ceration were not excluded from the study but were considered separately in the analysis.

RESULTS

Forty-eight patients were entered into the acyclovir group and 45 into the ara-A group. Demographically the patient groups were well- matched. The results are given in Table I. The majority of the patients presented with dendritic ulcers of one week’s duration or less.

Three patients in the acyclovir group and eight patients in the ara-A group failed to respond satisfactorily within 14 days. The time to complete healing for the remainder ranged from two to 14 days. Pa- tients in the acyclovir group healed at a significantly faster rate than those in the ara-A group (p <O.O 1, logrank analysis). A histogram representing the cumulative healing rate for dendritic ulcers is shown in Figure 1.

Eight patients with ameboid ulceration were entered, two in the ara-A group and six in the acyciovir group. One (small) ulcer healed in six days and one (large) ulcer failed to respond to ara-A. Five of the six acyclovir-treated ameboid ulcers healed in an average of 6.6 days.

Two patients experienced adverse reactions that may have been

l Zovirax@, Burroughs Wellcome.

The American Journal of Medicine Acyclovlr Symposium 311

ACYCLOVIR IN THE NORMAL HOST: OCULAR INFECTIONS-YOUNG ET AL

TABLE I Patient Characteristics According to Treatment

Acyclovir (n = 48)

Sex: male 32 female 16

Average age 51 Duration of symptoms: 1 week or less 39

2-3 weeks 5 4 weeks or more 4

Ulcer: simple dendritic 40 steroid-treated dendritic 2 ameboid 6

History of cutaneous herpes (% of patients) 42 Primary ocular infection (%) 35 Recurrent ocular infection (%) 65

Ara-A (n = 45)

30 15 52 37

6 2

39 4 2

42 59 41

SO-

E a 50- I 2 t! 2 40-

#

20-

I 1 2 3 4 5 6 7 a 9 10 11 12 13 14

STUDY DAY

Figure 7. Cumulative percent healing rate for patients treated with acyclovir an adenine arabinoside.

due to their antiviral medication. One patient who re- ceived acyclovir experienced a hypersensitivity reaction which could also have been caused by the atropine drops administered concurrently. One patient receiving ara-A complained of grittiness after use of the ointment. No other adverse effects were seen in this group of patients.

COMMENTS

Acyclovir and ara-A were both effective treatments for herpetic keratitis, although acyclovir achieved a more

rapid rate of healing than ara-A. The majority of patients responded within 14 days, and most of the treatment failures occurred in the ara-A group. The incidence of adverse reactions during the study was very low, with two cases of mild effects being reported. The hyper- sensitivity reaction in the patient in the acyclovir group could have been caused by other concurrent medica- tion. A further study is being carried out, concentrating on the ameboid ulceration. Acyclovir offers great po- tential in the management of herpetic ocular infec- tion.

312 Acyclovlr Symposium The American Journal ol Medlclne