Efﬁcacy of Valacyclovir vs Acyclovir for the Prevention
of Recurrent Herpes Simplex Virus Eye Disease:
A Pilot Study
ELISABETTA MISEROCCHI, GIULIO MODORATI, LAURA GALLI, AND PAOLO RAMA
To compare the efﬁcacy of one-year treat-
ment with valacyclovir vs acyclovir in preventing recur-
rence of the herpes simplex virus (HSV) eye disease.
Prospective, randomized, clinical trial pilot
Fifty-two immunocompetent patients with
a history of recurrent ocular HSV disease were treated at
the Ocular Immunology Service, San Raffaele Hospital,
Milan, Italy. Twenty-six patients were randomized to the
valacyclovir group (one 500 mg tablet daily), and 26
patients were randomized to the acyclovir group (one 400
mg tablet twice daily). The recurrence rate of ocular
HSV disease during 12 months of treatment and drug-
related side effects were monitored.
Recurrence of any type of ocular HSV
disease during the 12-month treatment period was 23.1%
in the valacyclovir group, compared with 23.1% in the
acyclovir group. No difference between the two groups
was observed regarding the nature, frequency, or severity
of adverse events. The most frequent adverse events were
nausea and headache.
One-year suppression therapy with
oral valacyclovir (500 mg tablet daily) was shown to be as
effective and as well tolerated as acyclovir (400 mg tablet
twice daily) in reducing the rate of recurrent ocular HSV
disease. (Am J Ophthalmol 2007;144:547–551. © 2007
by Elsevier Inc. All rights reserved.)
HE HERPES SIMPLEX VIRUS (HSV) IS THE LEADING
cause of corneal opacity and secondary visual loss in
the United States, other industrialized countries,
and developing nations throughout the world, affecting
some 450,000 people with 50,000 new and recurrent cases
Few studies have evaluated the epidemiologic
features of herpes keratitis in Europe; the largest and most
recent study, carried out in France, reported that the
overall incidence of herpetic keratitis is 31.5 per 100,000
person-years, 13.2 per 100,000 person-years for new cases,
and 18.3 per 100,000 person-years for recurrences.
Despite the availability of antiviral agents that are
effective in treating HSV eye disease, visual impairment
resulting from corneal scarring and uncontrolled intraoc-
ular inﬂammation can occur in many patients. The most
important and challenging problem in patients with recur-
rent ocular HSV is to limit and suppress recurrences to
avoid permanent visual loss. An analysis of the natural
history of ocular herpes simplex infection shows that the
number of recurrent episodes increases after onset: 9.6% at
one year, 22.9% at two years, and 63.2% at 20 years.
Acyclovir is an antiviral drug that selectively targets
virus-infected cells and has been shown to be effective in
treating and preventing genital herpes
It also has been evaluated in the therapy and
prophylaxis of HSV eye disease in a series of clinical trials
known as the Herpetic Eye Disease Study (HEDS).
HEDS recently showed that long-term prophylactic treat-
ment with oral acyclovir for more than 12 months reduces
ocular HSV recurrence.
Valacyclovir is the prodrug of acyclovir and is converted
rapidly to acyclovir after oral administration. The resulting
acyclovir bioavailability is three to ﬁve times more than
that of oral acyclovir. This higher plasma concentration of
acyclovir obtained from the oral administration of valacy-
clovir is similar to that achieved with intravenous acyclo-
Furthermore, intraocular and corneal concentrations
of acyclovir are known to correlate with plasma concen-
The purpose of this pilot study was to compare
the efﬁcacy of one-year treatment with oral valacyclovir
(500 mg daily) vs oral acyclovir (400 mg twice daily) in
preventing the recurrence of HSV eye disease.
PATIENTS WITH HSV EYE DISEASE REFERRED TO THE OCU-
lar Immunology and Uveitis Service at the San Raffaele
Hospital in Milan, Italy, were enrolled in the study and
were followed up from February 2004 through May 2005.
Eligible patients were more
than 18 years of age and had recurrence of ocular HSV
disease in one or both eyes in the preceding 12 months.
Accepted for publication Jun 1, 2007.
From the Department of Ophthalmology and Visual Sciences, San
Raffaele Scientiﬁc Institute, Milan, Italy (E.M., G.M., P.R.); and the
Clinic of Infectious Diseases, Vita-Salute San Raffaele University, Milan,
Inquiries to Elisabetta Miserocchi, Department of Ophthalmology and
Visual Sciences, San Raffaele Scientiﬁc Institute, Via Olgettina 60,
20132 Milan, Italy; e-mail: firstname.lastname@example.org
LL RIGHTS RESERVED