Treatment of herpes zoster ophthalmicus: A systematic

review and Canadian cost-comparison

Stacy Fan, BMSc,* Daniel Stojanovic, BHSc,* Monali S. Malvankar-Mehta, PhD,*,†
Cindy Hutnik, MD, PhD*,†
ABSTRACT ●
Objective: A systematic review and cost comparison were conducted to determine the optimal treatment of active herpes zoster
ophthalmicus (HZO) in immunocompetent adults.
Design: A literature search of MEDLINE, EMBASE, CINAHL, Cochrane Library, BIOSIS Previews and Web of Science,
ClinicalTrials.gov, International Clinical Trials Registry Platform, Networked Digital Library of Theses and Dissertations, and
Canadian Health Research Collection was performed. The search period was from January 1990 to March 2017.
Participants: Collectively, 516 immunocompetent patients with active HZO treated with oral antivirals were included.
Methods: Randomized controlled trials (RCTs) investigating treatment of active HZO in immunocompetent adults, with one oral
acyclovir monotherapy arm, were included. Studies fulfilling inclusion criteria were subjected to quality assessment and data
extraction. Provincial drug formularies were consulted to extrapolate cost comparison for investigated treatment regimens.
Results: A total of 1515 titles and abstracts and 9 full-text articles were assessed. Three RCTs met the inclusion criteria. Treatment
with oral acyclovir (800 mg 5 times daily for 10 days) was superior to placebo in the prevention of ocular manifestations. Oral
famciclovir (500 mg 3 times daily for 7 days) and valacyclovir (1000 mg 3 times daily for 7 days) resulted in comparable rates of
ocular manifestations relative to oral acyclovir (800 mg 5 times daily for 7 days). According to provincial drug formulary data,
famciclovir and valacyclovir are more affordable across Canada with the recommended dosing schedules.
Conclusions: Oral famciclovir and valacyclovir are reasonable alternatives to oral acyclovir for treatment of active HZO in
immunocompetent individuals. Their simpler dosing schedules are associated with a cost benefit that is consistent across
Canada.

Herpes zoster (HZ) is a reactivation of latent varicella
zoster virus (VZV) within the dorsal root ganglia, which
classically presents as a painful vesicular rash along a
unilateral dermatomal pattern.1 In 10%–20% of these
cases, reactivation occurs along the ophthalmic division of
the trigeminal nerve, resulting in herpes zoster ophthalmi-
cus (HZO).1,2 Although HZ is classically understood as a
self-limiting disease, viral replication within and around
the trigeminal nerve may cause ocular complications
through direct invasion, vascular and neural inflammation,
immune reactions, and tissue scarring.1,3
Fifty percent of patients with untreated HZO develop
ocular complications.4 Keratitis is the most common
ocular manifestation, followed by iritis, uveitis, conjunc-
tivitis, and scleritis.4 HZ in any dermatome may result
in postherpetic neuralgia, a chronic condition in which
pain persists or relapses, possibly years after HZ rash
has healed.5,6 More severe complications of HZO occur
when the optic nerve, retina, and central nervous
system are involved.1 The rates of ocular complica-
tions secondary to HZO increased 23% between
1970 and 2007.4 Despite HZO having a self-limiting
trajectory, early diagnosis and treatment is indicated
because of the potential for vision loss and other disease
sequelae.
Management of HZ with antiviral medication reduces
the duration and severity of acute zoster manifestation.7
Currently, the standard treatment is acyclovir, which is
both effective and well tolerated.1,8 Acyclovir is a nucleic
acid analogue that functions as a DNA chain terminator,
preventing viral replication. Acyclovir is activated specifi-
cally by viral thymidine kinases and becomes active only in
cells infected by DNA viruses, such as VZV and herpes
simplex virus 1 and 2.9–11 Topical acyclovir is associated
with increased ocular complications and more severe pain
in comparison to oral acyclovir.12 When administered
within 72 hours of onset of the initial skin lesion, oral
acyclovir 800 mg 5 times daily for 7 days reduces the
incidence of acute ocular complications, duration of acute
pain, and postherpetic neuralgia.13,14 Because of its
versatility, oral acyclovir is frequently administered in
HZO management.
The purpose of this study is to establish whether there is
any benefit to prescribing alternate antiviral medications to
guide the practice of Canadian ophthalmologists treating
HZO. This systematic review will investigate whether
there are any improvements in outcomes, primarily ocular
complications, when comparing oral acyclovir monother-
apy with other oral antiviral agents in the treatment of
active HZO in immunocompetent adults. A cost

& 2017 Canadian Ophthalmological Society.

Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jcjo.2017.08.005
ISSN 0008-4182/17

CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017 1

Treatment of active HZO in immunocompetent adults—Fan et al.
comparison of validated drug regimens will be extrapolated
using provincial drug formularies for the Canadian
context.
METHODS
Literature search
A literature search of MEDLINE, EMBASE, CINAHL,
the Cochrane Library, BIOSIS Previews, and Web of
Science was performed (see Appendix 1 for search strategy,
available online). Articles were restricted to publication in
the English language between January 1990 (the year
Dawson’s “Herpetic eye disease study”15 was published)
and March 28, 2017. OVID AutoAlerts were set up to
send monthly updates with any new literature. Monthly
updates were performed on HEED, PubMed, and
Cochrane Library databases.
Grey literature was identified by searching the Interna-
tional Clinical Trials Registry Platform, the Networked
Digital Library of Theses and Dissertations, Canadian
Health Research Collection, and ClinicalTrials.gov. Key
words included “herpetic eye disease” and “herpes zoster,”
combined with “acyclovir.” Searches were modified to
accommodate the unique terminology and syntax of each
database. The resultant list was then screened.
Study selection
Two reviewers (S.F. and D.S.) performed the literature
screening independently. A level 1 screening of articles by
title and abstract was conducted, followed by a level 2 full-
text screening. Discrepancies were settled through discus-
sion, and rationales for decisions were documented.
Selection criteria
Studies were included in the analysis if they (i) were
published as randomized controlled trials (RCTs) with at
least one oral acyclovir monotherapy arm, (ii) evaluated
patients who were immunocompetent adults (aged ≥18
years) diagnosed with HZO, (iii) were published in
English, and (iv) reported ocular outcomes after treatment
with oral antiviral.
Methodological Quality Assessment
The risk of study bias was assessed using the “Quality
Assessment Tool for Quantitative Studies” published by Effective
Public Health Practices.16 Two reviewers (S.F. and D.S.)
completed the assessment tool independently, and dis-
crepancies were resolved with discussion leading to con-
sensus. These data are summarized in Table 1.
Table 1—Quality assessment of included studies, based on Quality Assessment Tool for Quantitative Studies by Effective Public
Health Practices
Reference Selection Bias Study Design Confounders
Harding and Porter31 Weak Moderate Weak
Tyring et al.26 Strong Strong Moderate
Colin et al.32 Moderate Moderate Moderate
2 CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
Data extraction
The following information was extracted from the
selected articles: author, year of publication, study loca-
tion, study design, total patients enrolled in the study,
total patients who completed the study, patient demo-
graphic characteristics, treatment groups, dose and sched-
ule of interventions, duration of follow-up, and rates of
ocular sequelae.
Treatment effectiveness
Treatment effectiveness was determined based on treat-
ment outcomes reported in included studies. Data on rates
of intraocular involvement, development of ocular com-
plications, pain scores and time to resolution, and persis-
tent ocular lesions were obtained for various treatment
groups.
Cost comparison
The cost of prescribing the systemic/oral antiviral agents
was evaluated by consulting drug benefit formularies
for Ontario,17 Quebec,18 Manitoba,19 Saskatchewan,20
Alberta,21 British Columbia,22 Nova Scotia,23 Newfound-
land and Labrador,24 and Yukon25 as published by the
respective government agencies. Drug benefit formularies
were consulted for the remaining provinces and territories
in Canada but were excluded because of insufficient
information (i.e., did not include dollar value for cost of
medication). Dosing regimen was determined by the
recommendations made in the included studies. The cost
of various treatments was compared, and percentage
differences between treatments were obtained.
RESULTS
Search results
Figure 1 presents a PRISMA flowchart of study
selection. Our initial search yielded 1515 publications:
519 from Medline, 862 from EMBASE, and 134 from
CINAHL. A grey literature search identified 231 clinical
trials to be screened: 148 from the International Clinical
Trials Registry Platform, 16 from Clinicaltrials.gov, and
67 from Canadian Health Research Collection. A total of
275 duplicate studies were removed. Based on title and
abstract screening, we deemed 1462 articles ineligible and
retrieved 9 articles for full-text review. Of these, 1 was a
duplicate publication of the same trial and institution,26
4 did not compare oral monotherapy against oral acyclo-
vir,13,27–29 and 1 did not report the difference in outcomes
on intraocular sequelae between treatment groups and
Blinding Data Collection Methods Withdrawals and Drop Outs Global Rating
Weak Moderate Strong Weak
Moderate Moderate Strong Strong
Moderate Moderate Strong Strong
 Treatment of active HZO in immunocompetent adults—Fan et al.

European nations.26 Loss to follow-up was o20% in all

Identification

Records identified through

database searching
Additional records
identified through other
studies.
(n = 1515) sources (n = 231)

Data extraction
Records after duplicates removed
(n = 1471)
Characteristics and patient demographics of each study
are listed in Table 2. Included studies were published
Screening

between 1991 and 2001, with sample sizes ranging from

Records screened Records excluded 46 to 454 participants. All 3 studies were randomized,
(n = 1471) (n = 1462)
controlled parallel studies. All study participants were
diagnosed within 72 hours of onset of HZ cutaneous
lesion. All patients were immunocompetent adults (aged
Eligibility

Full-text articles assessed Full-text articles excluded,

for eligibility
(n = 9)
with reasons
(n = 6) ≥18 years).

Studies included in
qualitative synthesis
Treatment effectiveness
(n = 3) Harding’s study,31 which compared oral acyclovir 800 mg
Included

5 times daily for 10 days and placebo, found that intra-

ocular involvement was less frequent (30% vs 53%,
respectively), although not statistically significant, in
Fig. 1 — PRISMA flowchart illustrating the number of studies patients who received treatment for acute HZO (22%
identified at each level of screening and included studies. difference, 95% CI −0.7 to 51%, power 45%). Although
ocular complications, including anterior uveitis, stromal
keratitis, and sclerokeratitis, occurred in both groups, they
primarily described cutaneous findings of HZ.30 Three were described as less severe in the acyclovir arm. Addi-
remaining studies (516 subjects) were included in the tionally, active intraocular complications at 6 months of
systematic review. Three treatment regimens were extrapo- follow-up post-treatment were less common in the acy-
lated for subsequent cost comparison. clovir arm (5% chronic uveitis, in comparison to 42% in
the placebo group, p ¼ 0.023). Self-reported pain scores
were also lower in the acyclovir group, with a significant
Methodological quality assessment difference noted from 2 to 6 months of follow-up.
The quality of included studies was determined based Tyring et al.26 compared treatment of HZO with oral
on methodological assessment. Results are shown in acyclovir 800 mg 5 times daily for 7 days and oral
Table 1. One study was completed in England,31 one in famciclovir 500 mg 3 times daily for 7 days. Patients
France,32 and the final study was a multinational trial with were followed for up to 6 months after treatment. They
contributions from the United States and multiple found that ocular manifestations were similar between

Table 2—Data extraction from included studies

Total Pts Total Pts Patient Dosing No.of Dosing No. of Follow-up,
Author Location Enrolled Completed Demographics Group 1 Schedule Pts Group 2 Schedule Pts months
Harding and Liverpool 46 42 Male: 15 Acyclovir 5× daily 24 Placebo 5× daily 18 6
Porter31 Female: 27 800 mg ×10 d ×10 d
Mean age: 66 yrs
Presenting in under 48
hours: Not statistically
significant (p 4 0.1)

Tyring et al.26 87 454* 378 Male: 213 Acyclovir 5× daily 246 Famciclovir 3× daily 251 6
centres, Female: 241 800 mg ×7 d 500 mg ×7 d
worldwide Mean age:58 yrs
Presenting in under 48
hours: 252

Colin et al.32 5 centres, 110 96 Male: 53 Acyclovir 5× daily 54 Valacyclovir 3× daily 56 6

France Female: 57 800 mg ×7 d 2 × 500 mg ×7 d
Mean age: 60 yrs
Presenting in under 48
hours: 95

⁎
499 patients were enrolled in the study; however, 42 patients in the acyclovir arm were excluded from the intention-to-treat analysis because they were provided with acyclovir not
bioequivalent to commercially available acyclovir.

CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017 3

Treatment of active HZO in immunocompetent adults—Fan et al.

both groups (odds ratio [OR] 0.99, 95% CI 0.68–1.45)
with similar rates of severe manifestations (anterior uveitis,
keratic precipitates, stromal and disciform keratitis, irido-
cyclitis, and glaucoma). Additionally, they noted that more
than double the number of patients in the acyclovir arm
compared with famciclovir experienced a decline in visual
acuity, although this difference was not statistically sig-
nificant (OR ¼ 0.4, 95% CI 0.15–1.08). No information
regarding time to pain cessation or new lesion cessation
was recorded in this trial.
Colin et al.32 compared the efficacy and safety of oral
acyclovir 800 mg 5 times daily with valacyclovir 500 mg
3 times daily, both for 7 days. They found that a
comparable percentage of participants experienced ocular
complications, including conjunctivitis, superficial kerati-
tis, stromal keratitis, and uveitis (31% acyclovir, 29%
valacyclovir, p ¼ 0.74). Furthermore, 6% of patients in
the acyclovir arm, compared with 4% in the valacyclovir
arm, had ocular lesions that persisted at 2 months of
follow-up. The incidence of ocular lesions at 6 months
stayed the same in the valacyclovir group, but declined to
2% in the acyclovir group.
Adverse events (AEs) reported in all 3 studies were
similar.26,31,32 The most common AEs included nausea,
vomiting, and headache. Other AEs such as anorexia,
malaise, dyspepsia, heartburn, eyelid or facial edema, and
depression were also reported.
Cost comparison
Cost of treatment was calculated based on the unit cost
of medication and the recommended dosing schedules:
800 mg oral acyclovir 5 times per day, 1000 mg oral
valacyclovir 3 times per day, and 500 mg oral famciclovir
3 times per day, all for a 7-day period.13,30,33 Figure 2
summarizes the cost comparison of oral acyclovir, valacy-
clovir, and famciclovir in Ontario, Quebec, Manitoba,
Saskatchewan, Alberta, British Columbia, Nova Scotia,
Newfoundland and Labrador, and Yukon.
DISCUSSION
The aim of this review was to investigate oral antiviral
medications used in the management of active HZO and
to determine whether a benefit exists for a particular agent.
Occurrence of ocular complications secondary to HZO
was our primary outcome of interest.
Three RCTs, each featuring different antiviral regimens,
were included in the systematic review. One trial com-
pared a 10-day course of 800 mg acyclovir 5 times daily

Fig. 2 — (A) Cost comparison of oral antivirals. (B) Percentage cost difference compared to 500 mg valacyclovir tablets. Dosing
schedules- acyclovir: 1 x 800 mg tablets 5x daily, famiciclovir: 1 x 500 mg tablets 3x daily, valacyclovir 2 x 500 mg tablets 3x
daily; (all for 7 days).

4 CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017

 Treatment of active HZO in immunocompetent adults—Fan et al.
with placebo and concluded that active treatment was
effective in the prevention of ocular manifestations of
HZO.31 The 2 remaining studies compared a 7-day course
of 800 mg acyclovir 5 times daily with 1000 mg
valacyclovir 3 times daily32 and 500 mg famciclovir 3 times
daily.26 Although an improvement from the predicted
natural course of disease was noted, neither study detected
a significant difference in the incidence of ocular mani-
festations of HZO after antiviral treatment.
Taken together, these results suggest that oral famci-
clovir and valacyclovir are equally as effective as oral
acyclovir for the treatment of active HZO in immuno-
competent adults. Valacyclovir is the prodrug of acyclovir
and has an identical mechanism of action, after biochem-
ical conversion in the liver. Famciclovir is the prodrug
form of penciclovir. They share a common mechanism
with acyclovir once metabolized into the active forms.34
Famciclovir and valacyclovir have higher bioavailabilities
and more favourable pharmacokinetic properties relative
to their parent drugs. This may account for the compa-
rable effectiveness of famciclovir and valacyclovir at less-
frequent dosing schedules in comparison to acyclovir.35,36
Their metabolites, penciclovir and acyclovir, respectively,
penetrate the blood–ocular barrier. However, vitreous
levels of acyclovir have been shown to be highest after
administration of oral valacyclovir.37,38 Thus, current
research suggests that administration of oral acyclovir,
famciclovir, or valacyclovir for treatment of active HZO in
immunocompetent adults is indicated as best practice.
To provide further guidance to Canadian ophthalmol-
ogists, a direct cost comparison of the antiviral regimens
was conducted using data from provincial drug formula-
ries. A cost benefit is consistently noted across Canada
with valacyclovir and famciclovir regimens (Fig. 2) due to
the decreased number of doses required to complete a
course.
There are concerns with all 3 studies included in this
systematic review. Harding’s study included a small
sample size, had limited information on patient demo-
graphics, an unclear method of randomization, and a lack
of intention-to-treat analysis that resulted in a risk of
selection bias and confounding.31 Once a patient devel-
oped severe ocular manifestations of disease, steroid drops
were added to their treatment regimen, confounding
data on time to resolution. Colin’s trial did not
specify the method of randomization but was otherwise
well-regarded.32 Tyring’s study excluded 42 participants
from the intention-to-treat analysis because participants
were initially given acyclovir, which was not bioequivalent
to the commercially available product and generated a
moderate risk of selection bias.26
Our present review warrants cautious interpretation
because of 2 significant limitations. First, the external
validity of included studies in the Canadian context is
debatable. Although treatment arms across RCTs show a
reasonable level of comparability with regard to age, sex,
and race, study participants are primarily Caucasian
individuals of European descent. Furthermore, none of
the included studies considered the socioeconomic status
of participants. Consequently, these results may not be
suitable for extrapolation across racialized or low-socio-
economic-status populations of Canada. Additionally,
these studies do not provide insight into optimal manage-
ment of HZO in pregnant women or individuals with
renal damage (both may require adjusted dosing regi-
mens). Second, direct comparison within this systematic
review is difficult because there is no consistent treatment
regimen among the studies. We were therefore unable to
conduct a meta-analysis. Although all included studies
contained an oral acyclovir arm, the duration of treatment
was inconsistent (10 days31 vs 7 days26,32). This limits the
conclusions that can be drawn regarding the duration of
treatment because none of the included studies made this
comparison directly. Any attempt to directly compare the
10-day arm against the two 7-day arms would eliminate
the benefits of randomization from individual studies and
result in selection bias.
Limitations of the cost comparison were also noted.
Limiting the cost comparison to Canadian provinces and
territories at a specific point in time may hamper the
generalizability. However, this is an unavoidable factor
given the dynamic and constantly changing cost of
medications, which are both temporally and geographi-
cally dependent. Nevertheless, this method of cost-com-
parison is noteworthy and applicable for all clinicians who
seek to optimize treatment in a cost-effective era of health
care delivery. The cost comparison did not include the 10-
day trial of acyclovir as described in Harding’s study
because this was not the standard dose reflected in the
modern literature or practice.13
In summary, oral famciclovir and valacyclovir appear to be
equally effective compared with oral acyclovir in the treat-
ment of active herpetic eye disease caused by reactivation of
latent VZV. Simpler dosing schedules of the prodrugs are
associated with cost savings to the Canadian health care
system (Fig. 2). This finding is significant because less-
frequent dosing regimens may help improve patient adher-
ence, persistence, and compliance. Therefore, we conclude
that famciclovir and valacyclovir may be the superior treat-
ment of choice for HZO in the present Canadian context.
This directly challenges the widespread perception that the
oldest drugs within a class, which also happen to have the
least desirable dosing regimen, are the most cost-effective
choice. This emphasizes the importance of considering
efficacy, safety, dosing regimens, and cost when making
the best therapeutic decisions for patients.
REFERENCES
1. Liesegang TJ. Herpes zoster ophthalmicus natural history, risk
factors, clinical presentation, and morbidity. Ophthalmology.
2008;115:S3-12.
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017 5
Treatment of active HZO in immunocompetent adults—Fan et al.
2. Harding SP, Lipton JR, Wells JC. Natural history of herpes zoster
ophthalmicus: predictors of postherpetic neuralgia and ocular
involvement. Br J Ophthalmol. 1987;71:353-8.
3. Naumann G, Gass JD, Font RL. Histopathology of herpes zoster
ophthalmicus. Am J Ophthalmol. 1968;65:533-41.
4. Yawn BP, Wollan PC, St Sauver JL, Butterfield LC. Herpes zoster
eye complications: rates and trends. Mayo Clin Proc. 2013;
88:562-70.
5. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent
herpes zoster and postherpetic neuralgia in older adults. N Engl J
Med. 2005;352:2271-84.
6. Tontodonati M, Ursini T, Polilli E, et al. Post-herpetic neuralgia. Int
J Gen Med. 2012;5:861-71.
7. Gross G, Doerr HW. Herpes zoster guidelines of the German
Dermatological Society. J Clin Virol. 2003;27:308-9.
8. Herne K, Cirelli R, Lee P, Tyring SK. Antiviral therapy of acute
herpes zoster in older patients. Drugs Aging. 1996;8:97-112.
9. Brigden D, Whiteman P. The mechanism of action, pharmacoki-
netics and toxicity of acyclovir—a review. J Infect. 1983;6:3-9.
10. Morton P, Thomson AN. Oral acyclovir in the treatment of herpes
zoster in general practice. N Z Med J. 1989;102:93-5.
11. McKendrick MW, McGill JI, White JE, Wood MJ. Oral acyclovir
in acute herpes zoster. Br Med J (Clin Res Ed). 1986;293:1529-32.
12. Neoh C, Harding SP, Saunders D, et al. Comparison of topical and
oral acyclovir in early herpes zoster ophthalmicus. Eye (Lond).
1994;8:688-91.
13. Hoang-Xuan T, Büchi ER, Herbort CP, et al. Oral acyclovir for
herpes zoster ophthalmicus. Ophthalmology. 1992;99:1062-70. dis-
cussion 70–1.
14. Crooks RJ, Jones DA, Fiddian AP. Zoster-associated chronic pain:
an overview of clinical trials with acyclovir. Scand J Infect Dis Suppl.
1991;80:62-8.
15. Dawson CR. The herpetic eye disease study. Arch Ophthalmol.
1990;108:191-2.
16. Effective Public Health Practice Project. Quality assessment tool for
quantitative studies. Available from: http://www.ephpp.ca/PDF/
Quality_Assessment_Tool_2010_2.pdf. Accessed March 27, 2017.
17. Ontario Drug Benefit Formulary/Comparative Drug Index. 2017.
Available from: http://www.health.gov.on.ca/en/pro/programs/
drugs/formulary42/edition_42.pdf. Accessed July 24, 2017.
18. Quebec List of Medications. 2017. Available from: http://www.
ramq.gouv.qc.ca/SiteCollectionDocuments/liste_med/liste_med_co
r1_2017_04_01_en.pdf. Accessed July 24, 2017.
19. Manitoba Drug Interchangeability Formulary. 2017. Available from:
http://www.gov.mb.ca/health/mdbif/docs/schedule.pdf. Accessed
July 24, 2017.
20. Saskatchewan Ministry of Health Drug Plan. 2017. Available from:
http://formulary.drugplan.ehealthsask.ca/default.aspx. Accessed July 24,
2017.
21. Alberta Health Healthcare Insurance. 2017. Available from: https://
idbl.ab.bluecross.ca/idbl/search.do. Accessed July 24, 2017.
22. BC PharmaCare Formulary Search. 2017. Available from: https://
pharmacareformularysearch.gov.bc.ca/faces/Search.xhtml. Accessed
July 24, 2017.
23. Nova Scotia Formulary. 2017. Available from: https://novascotia.ca/
dhw/pharmacare/documents/formulary.pdf. Accessed July 24, 2017.
24. The Newfoundland and Labrador Interchangeable Drug Products
Formulary. 2017. Available from: http://www.health.gov.nl.ca/
health/nlpdp/formularyvol76.pdf. Accessed July 24, 2017.
25. Yukon Drug Formulary. 2017. Available from: http://apps.gov.yk.
ca/drugs/f?p=161:9000:3635077145702816. Accessed July 24,
2017.
6 CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
26. Tyring S, Engst R, Corriveau C, et al. Famciclovir for ophthalmic
zoster: a randomised aciclovir controlled study. Br J Ophthalmol.
2001;85:576-81.
27. Cellini M, Baldi A, Caramazza N, De Felice GP, Gazzaniga A.
Epidermal growth factor in the topical treatment of herpetic corneal
ulcers. Ophthalmologica. 1994;208:37-40.
28. Chen Y-H. Observation of oral acyclovir combined with sodium
hyaluronate and fluorometholone eye drops on the treatment of
herpes zoster keratitis. Int Eye Sci. 2014;14:729-30.
29. Porter SM, Patterson A, Kho P. A comparison of local and systemic
acyclovir in the management of herpetic disciform keratitis. Br J
Ophthalmol. 1990;74:283-5.
30. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ.
Valaciclovir compared with acyclovir for improved therapy for
herpes zoster in immunocompetent adults. Antimicrob Agents
Chemother. 1995;39:1546-53.
31. Harding SP, Porter SM. Oral acyclovir in herpes zoster ophthalmi-
cus. Curr Eye Res. 1991;10(Suppl):177-82.
32. Colin J, Prisant O, Cochener B, Lescale O, Rolland B, Hoang-Xuan
T. Comparison of the efficacy and safety of valaciclovir and acyclovir
for the treatment of herpes zoster ophthalmicus. Ophthalmology.
2000;107:1507-11.
33. Tyring SK. Efficacy of famciclovir in the treatment of herpes zoster.
Semin Dermatol. 1996;15:27-31.
34. De Clercq E. Antiviral drugs in current clinical use. J Clin Virol.
2004;30:115-33.
35. Ormrod D, Goa K. Valaciclovir: a review of its use in the
management of herpes zoster. Drugs. 2000;59:1317-40.
36. Simpson D, Lyseng-Williamson KA. Famciclovir: a review of its use
in herpes zoster and genital and orolabial herpes. Drugs.
2006;66:2397-416.
37. Huynh TH, Johnson MW, Comer GM, Fish DN. Vitreous
penetration of orally administered valacyclovir. Am J Ophthalmol.
2008;145:682-6.
38. Schenkel F, Csajka C, Baglivo E, et al. Intraocular penetration
of penciclovir after oral administration of famciclovir: a population
pharmacokinetic model. J Antimicrob Chemother. 2013;68:1635-41.
Footnotes and Disclosure:
The authors have no proprietary or commercial interest in any
materials discussed in this article.This article includes online-only
material.
Appendix 1 can be found on the CJO web site at http://pubs.
nrc-cnrc.gc.ca/cjo/cjo.html. It is linked to this article in the
online contents of the xxx 20xx issue.
From the *Schulich School of Medicine & Dentistry, Western
University, London, Ont; †Ivey Eye Institute, St. Joseph’s Health
Care London, London, Ont.
Originally received May. 10, 2017. Final revision Jul. 29, 2017.
Accepted Aug. 10, 2017.
Correspondence to Cindy Hutnik, MD, PhD, Ivey Eye Institute,
St. Joseph’s Health Care London, 268 Grosvenor Street,
London, Ont. N6A 4V2; cindy.hutnik@sjhc.london.on.ca.