Ocular Immunology and Inflammation

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Review for Disease of the Year: Varicella Zoster

Virus-Induced Anterior Uveitis

Ilknur Tugal-Tutkun, Luca Cimino & Yonca Aydin Akova

To cite this article: Ilknur Tugal-Tutkun, Luca Cimino & Yonca Aydin Akova (2017): Review for
Disease of the Year: Varicella Zoster Virus-Induced Anterior Uveitis, Ocular Immunology and
Inflammation, DOI: 10.1080/09273948.2017.1383447

To link to this article: http://dx.doi.org/10.1080/09273948.2017.1383447

Published online: 12 Oct 2017.

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 Ocular Immunology & Inflammation, 2017; 00(00): 1–7
© Taylor & Francis Group, LLC
ISSN: 0927-3948 print / 1744-5078 online
DOI:10.1080/09273948.2017.1383447

REVIEW ARTICLE

Review for Disease of the Year: Varicella Zoster

Virus-Induced Anterior Uveitis
1 2 3
Ilknur Tugal-Tutkun, MD , Luca Cimino, MD , and Yonca Aydin Akova, MD

1
Istanbul Faculty of Medicine, Department of Ophthalmology, Istanbul University, Istanbul, Turkey, 2Ocular
Immunology Department, Azienda Unità Sanitaria Locale di Reggio Emilia-IRCCS, Reggio Emilia, Italy, and
3
Department of Ophthalmology, Bayindir Kavaklidere Hospital, Ankara, Turkey
Downloaded by [Southern Cross University] at 22:48 13 October 2017

ABSTRACT
Varicella zoster virus (VZV)-induced anterior uveitis (AU) may complicate the course of primary varicella
infection typically seen in children. In adults, especially with advanced age, VZV AU is more commonly
associated with herpes zoster ophthalmicus (HZO) with or without skin rash affecting the distribution of the
ophthalmic nerve due to reactivation of the latent VZV in the trigeminal ganglion. While it is typically a mild self-
limiting AU in primary infection, HZO AU is often accompanied by keratitis, may have a chronic recurrent
course, and lead to sectoral iris atrophy, pupillary distortion, and ocular hypertension. Diagnosis is often clinical
and proven by analysis of aqueous humor for viral genome or antiviral antibodies. Systemic antiviral agents and
topical steroids are the mainstay of treatment. Visual prognosis is favorable with timely diagnosis and appro-
priate treatment.
Keywords: Antiviral treatment, herpes zoster ophthalmicus, primary varicella infection, varicella zoster virus,
viral anterior uveitis, visual prognosis

Varicella zoster virus (VZV)-associated viral syndromes
include varicella (chickenpox) disease which is the pri-
mary contagious disease that presents in early childhood,
herpes zoster (HZ) (shingles) that occurs later in life with
reactivation of the latent virus, and intrauterine varicella
infection when a pregnant woman acquires primary
infection.1,2 Ocular involvement can occur in all as well
as in association with varicella vaccination.3
Varicella-zoster virus is a double-stranded DNA
virus of the Herpesviridae family. It is ubiquitous
and highly neurotrophic. VZV is distributed world-
wide, but is more prevalent in temperate climates.
The primary infection, typically more common in chil-
dren, is associated with a febrile illness and general-
ized varicella dermatitis, a pustular rash that is self-
limited. During primary infection, viral particles of
VZV migrate centripetally from the infected skin
along sensory nerve endings and gain access to the
sensory ganglia, where, similar to herpes simplex
virus (HSV), they enter into a latent state. Following
primary infection, the host’s immune system
suppresses viral replication, and viral particles can
then remain dormant for years, most commonly in
spinal root and cranial nerve ganglia. 1
Herpes zoster is characterized by the development
of a localized vesicular rash and neuropathic pain in
the distribution of the dermatome of the involved
cranial or spinal nerve, upon reactivation of VZV.1
Herpes zoster occurs when host immunity fails to
suppress the virus, which can be due to psychological
stress, immunosuppression, or direct trauma.4–6
Therefore, the virulence of VZV and the immune sta-
tus of the host are primary factors leading to the
development of HZ. Immunocompromised patients,
such as in HIV infection, have a 15 times greater risk
of developing HZ,7 and are more likely to have a
prolonged illness, more likely to recur, and more likely
to develop myelitis and vasculopathy.8 Moreover, the
incidence and severity of HZ increase with advancing
age, with patients over the age of 60 at the highest
risk.9 The disease is rare in children, with 7% of HZ
occurring in childhood10; varicella infection of the

Received 19 August 2017; revised 16 September 2017; accepted 19 September 2017

Correspondence: Prof. Dr. Ilknur Tugal-Tutkun, Göz Hastaliklari Anabilim Dali, Istanbul Universitesi Istanbul Tip Fakultesi, Çapa, Istanbul
34390, Turkey. E-mail: itutkun@yahoo.com
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ioii.

1
 2 I. Tugal-Tutkun et al.
mother during gestation results in neuronal latency in
the fetus, with a probable reactivation as HZ in
childhood.2
The prevalence of HZ is about 1 million new cases
per year in the United States11; its incidence is 4–4.5
per 1000 person-year.12 Patients aged 50 and older
represent 80% of cases12,13; 92% of people with HZ
are not immunocompromised.14
The trigeminal dermatomes are most commonly
affected by clinically manifest HZ.15,16 The involve-
ment of the first or ophthalmic division of this nerve
is called herpes zoster ophthalmicus (HZO),17 and it
is about 20 times more common than the involve-
ment of the second or third division. The ophthalmic
division gives rise to three terminal branches: the
lacrimal, frontal, and nasociliary branches. Within
that division, the frontal nerve is the most com-
Downloaded by [Southern Cross University] at 22:48 13 October 2017
monly involved and innervates the upper lid, fore-
head, and some superior conjunctiva. The nasociliary
branch, the primary sensory nerve to the eyeball,
innervates the skin of the tip of the nose and divides
further into the long ciliary nerves, which provide
sensory innervation to the globe, including the
sclera, cornea, and uvea.17 For this reason, the invol-
vement of the tip of the nose, called Hutchinson’s
sign, is highly correlated with ophthalmic
involvement.18,(Figure 1) Ocular disease can also
occur in the absence of skin rash (zoster sine
herpete).19 The incidence of HZO was found to be
30.9 per 100,000 person-years in a retrospective
population-based cohort study in Hawaii.20
FIGURE 1. Typical skin rash extending to the tip of the nose in
a patient with HZO.
ANTERIOR UVEITIS IN PRIMARY
VARICELLA INFECTION
The most common ocular findings in primary varicella
infection are eyelid blisters and conjunctivitis that
appear during the eruption of skin lesions. Superficial
punctate keratitis may appear a few days after the
onset of skin rash.21 Atypical dendritic lesions, disci-
form stromal keratitis, interstitial keratitis, and stromal
immune rings have also been reported.22–24
Anterior uveitis (AU) is relatively uncommon,
reported in 25% of cases in a series of 24 children with
lesions on their eyelids.21 In another series of 82 chil-
dren, 25% were found to have AU without lesions on
their eyelids.25 In a prospective study of 100 consecutive
children with primary varicella, Sungur et al.26 found
no association between the presence of eyelid lesions
and development of uveitis or between the severity of
chickenpox and severity of ocular involvement. In their
series, 21% of the patients had ocular involvement, with
eyelid lesions in 28.6%, conjunctivitis in 38.1%, AU in
57.1%, and disciform keratouveitis in 4.8%.26 In adults,
chickenpox is uncommon. Gargouri et al. have 27
reported unilateral or bilateral acute AU in three of
five adult patients who developed ocular involvement
associated with primary varicella infection.
In primary varicella infection, AU is usually mild,
typically appears 3–5 days after the onset of skin erup-
tion, and is mostly self-limiting.28 Fine keratic precipi-
tates are usually seen, and small round atrophic spots in
the iris stroma appear to be a typical feature.29 A dis-
torted pupil and sectoral iris atrophy may also develop.
Internal ophthalmoplegia is a rare, but serious compli-
cation of primary varicella infection, resulting in a per-
manently unreactive pupil and accommodation
loss.22,30
Optic neuritis, neuroretinitis, retinitis, and acute ret-
inal necrosis have been rarely reported, with a higher
risk in immunocompromised children who have con-
tracted chickenpox.31
ANTERIOR UVEITIS IN HERPES ZOSTER
OPHTHALMICUS
Patients with HZO present with skin lesions in the
distribution of the ophthalmic nerve, not crossing the
midline, usually following a prodromal period of
fever, malaise, paraesthesia, headache, and ocular
pain. Ocular involvement occurs in about 50% of
patients with HZO, 17 but it has been reported to
have reduced to 2% to 29% of patients treated with
antivirals.32,33 The disease is typically unilateral; how-
ever, bilateral involvement has been reported in up to
13% of cases,34 occurring especially in patients with
underlying immunosuppression or severe atopy. In
the course of the disease, the eyelids, conjunctiva,
Ocular Immunology & Inflammation

cornea, sclera, intraocular tissues, optic nerve, and
orbital structures may become involved early, due to
direct damage from viral infection, or later as a result
of vasculitis and immune reaction to the viral antigens.
In a population-based study of 7370 subjects with HZ
in the USA, 2.5% of cases had eye involvement; and
keratitis was the most frequent ocular complication
(76.2%), followed by uveitis/iritis (46.6%), and con-
junctivitis (35.4%).35 In a hospital-based population in
the USA, 70% of patients with HZO had eye involve-
ment; and the most common findings were conjuncti-
vitis or episcleritis in 53%, epithelial keratitis in 31%,
and uveitis in 32%.36 In a recent series of 259 patients
with HZO reported from Hong Kong, China, 65.6%
had ocular manifestations despite initiation of antiviral
treatment within 72 hours of symptom onset in 96.5%
of the patients; conjunctivitis was the most common
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manifestation (56.8%), followed by AU (17.8%) and
stromal keratitis (6.6%).37 Anterior uveitis with or
without keratitis was the most common manifestation
(60.8%) in another series of HZO, where a much higher
frequency of ocular involvement (92.2%) has been
reported, presumably due to a referral bias.34
Adnexal involvement and keratitis with corneal
hypoesthesia were the other common manifestations
recorded in 58.8% and 31.4% of cases, respectively, in
the latter series.34
Anterior uveitis may develop during the acute phase
of HZO when there may also be lid edema and vesicu-
lar skin lesions, conjunctivitis, episcleritis, scleritis, a
coarse punctate epithelial keratitis or dendriform cor-
neal epithelial lesions. More commonly, AU is seen
2–4 weeks after the onset of HZO, and may be accom-
panied by stromal keratitis. It may also develop many
years after the initial episode of HZO that may have
occurred with or without typical skin lesions.
In series where a clinical diagnosis of VZV AU was
based on an active or past episode of HZO, granulo-
matous keratic precipitates were reported in up to 58%
of eyes, focal iris atrophy in 25%, and intraocular
pressure elevation/glaucoma in 23.5%-38% of
FIGURE 2. Extensive iris atrophy (A) and transillumination (B) due to unilateral VZV AU confirmed by the presence of VZV DNA in
the aqueous humor in a patient without history of HZO.
© 2017 Taylor & Francis Group, LLC
VZV Anterior Uveitis 3
eyes.34,38 Anterior uveitis was associated with keratitis
in 51%-77% of eyes with VZV AU.34,38 Kahloun et al.34
have also reported posterior synechiae in 16%, Koeppe
nodules in 6.5%, and pupillary distortion in 6.5% of
eyes. While Kahloun et al.34 reported that 83.8% of
their cases had an acute AU, 6.4% had recurrent and
6.9% had a chronic course, the disease course tended
to be either chronic (42%) or recurrent (38%) in the
series reported by Miserocchi et al.38 In another series
of 34 patients with HZO-associated AU, a uniphasic
course was reported in 68% and a chronic relapsing
course in 32%.39 Secondary glaucoma was reported in
56% of the cases in the latter series.39 Ocular hyperten-
sion was found to be a significant risk factor for recur-
rent or chronic eye disease in HZO in another study.36
Unilateral involvement, granulomatous keratic pre-
cipitates, patchy or sectoral iris atrophy, pupillary dis-
tortion, and acute IOP spikes at recurrences are highly
suggestive features for a clinical diagnosis of herpetic
AU.40 In the absence of a history of HZO, the diagno-
sis of VZV anterior uveitis can only be made by
laboratory investigation. (Figure2)
LABORATORY DIAGNOSIS
Laboratory data are essential for a definitive diagnosis,
such as in cases of HZ sine herpete, especially those
presenting with hyphema that obscures ocular
inflammation.41,42
About 90% of healthy adult population have detectable
serum titers of VZV antibodies; therefore, high IgM titers
(>1:640) or seroconversion is needed for serologic confir-
mation. Analysis of intraocular fluids is increasingly per-
formed for a more reliable confirmation of clinical
diagnosis of viral AU and in order to differentiate
between various viral etiologies of AU. The production
of specific intraocular antibodies as determined by a
Goldmann–Witmer coefficient (GWC) of 3 or more and/
or a positive polymerase chain reaction (PCR) for viral
genome in the aqueous humor are considered as proof of
 4 I. Tugal-Tutkun et al.
viral etiology.43 The causative agents are mainly identified
by PCR during the first weeks. Multiplex PCR is used to
qualitatively determine the genomic DNA of different
viruses; and real-time PCR is used to measure the viral
load of the causative agent.44 Beyond 2 months after the
onset of active disease, viral DNA may not be detected.
Positive GWCs are found throughout the clinical course of
the ocular infections but are more frequent at later time
points. Therefore, PCR and GWC analysis are compli-
mentary for the diagnosis of infectious uveitis.43,45
COMPARISON OF CLINICAL FEATURES
AND COMPLICATIONS BETWEEN PROVEN
VZV ANTERIOR UVEITIS AND OTHER
VIRAL ANTERIOR UVEITIDES
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In a series of 24 patients with unilateral viral AU with
sectoral iris atrophy in the absence of keratitis, the causa-
tive agent was identified as herpes simplex virus (HSV) in
83% and VZV in 13% by analysis of intraocular fluids for
antibody production or detection of viral DNA.46 Patients
with VZV AU were significantly older than those with
HSV AU (mean age, 65 vs 34 years, respectively).46
Demographic and clinical features as well as com-
plications of AU have been compared between
groups of patients with VZV, HSV, CMV, or rubella
virus (RV)-associated AU in three series of viral AU
where the viral etiology was proven by intraocular
fluid analysis.47,48,49Table 1 shows the reported fea-
tures of VZV AU in these series. Wensing et al.
reported that only 1 of 10 patients with proven VZV
AU had a previous history of HZO; focal iris atrophy
was less common in VZV than in HSV (10% vs 48.6%,
respectively); diffuse iris atrophy was not seen in any
eye with VZV, whereas it was present in RV (14.8%)
and HSV AU (8.1%); vitritis occurred more frequently
TABLE 1. Clinical findings and complications of varicella zoster virus anterior uveitis in studies where the diagnosis was proven by
intraocular fluid analysis.
Clinical findings and complications Wensing et al.47 N = 10 %
Granulomatous/pigmented keratic precipitates N/A*
Corneal involvement 25**
Epithelial N/A
Stromal N/A
Endotheliitis N/A
Segmental iris atrophy 10
Posterior synechiae 40
Iris nodules N/A
Ocular hypertension 50
Glaucoma 30
Cataract 30
Anterior vitreous cells 83***
* Keratic precipitates were observed in 70% of cases; however, their nature was not reported.
** Previous keratitis was reported in 2 of 8 patients.
*** Anterior vitreous cells were reported in 5 of 6 patients.
in VZV (83%) and RV (88%) than in HSV AU (43%);
and glaucoma developed at similar rates in all three
groups (18%-30%). In the series reported by Takase
et al.,48 dermal blisters of HZO were present in 20% of
cases with VZV AU; segmental iris atrophy was seen
in 40% of eyes with VZV, 13% of eyes with HSV, but
none of the eyes with CMV AU; by contrast, diffuse
iris atrophy was observed in 33% of eyes with CMV,
13% of HSV, and only 5% of eyes with VZV AU.
Anterior vitreous cells were found at a similar fre-
quency (11%-25%), and the incidence of ocular hyper-
tension was high in all three groups (63%-85%).48
Babu et al.49 have found no significant differences
between HSV and VZV AU except for a previous
history of HZ in VZV AU.
Viral loads observed in VZV AU were significantly
higher than viral loads observed in CMV AU.46 It has
been reported that the viral load of VZV in the aqueous
humor correlated with the intensity of iris atrophy and
pupil distortion but not with ocular hypertension in
patients with HZO or HZ sine herpete.44
TREATMENT
All patients with acute HZO should receive antiviral
therapy in order to shorten the course of the disease
and reduce the frequency and severity of ocular com-
plications. The treatment of acute HZO infection with
oral acyclovir 800 mg five times daily, valacyclovir
1000 mg three times daily, or famciclovir 500 mg
three times daily for 10 days, given within 72 hours
of the onset of symptoms reduces the incidence and
severity of anterior uveitis 32,33,50–52 Valacyclovir, a
prodrug of acyclovir and famciclovir, a prodrug of
penciclovir, with improved bioavaliability, have both
been shown to be equivalent in HZO treatment. In
Takase et al.48 N = 20 % Babu et al.49 N = 24 %
85 87.5
25 75
5 0
0 N/A
20 N/A
40 29.2
30 N/A
5 N/A
85 25
15 12.5
(glaucoma surgery) (glaucoma surgery)
N/A 16.7
25 N/A
Ocular Immunology & Inflammation

general, these drugs are safe and well tolerated.
Because of dosing advantages, valacyclovir and famci-
clovir may be preferred to acyclovir for the treatment
of HZO. 52,53 A dose adjustment may be required in
patients with renal insufficiency.
There is no standard therapeutic approach to HZO
related AU. Topical antiviral therapy has little or no
effect on the iridocylitis or trabeculitis. Systemic antiviral
agents including acyclovir, valacyclovir and famciclovir
attain excellent levels of anterior chamber concentration
and are beneficial to treat iridocyclitis and trabeculitis.
Chronic HZO AU should be treated with oral antiviral
therapy for at least 4 weeks or until the disease is under
complete control. 11,14,46,54–56 Herpes zoster opthalmicus
uveitis requires higher oral antiviral doses than HSV
uveitis due to the higher inhibitory concentration of
antivirals required for VZV compared with HSV.
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Maintenance therapy with oral acyclovir 400 mg three
times daily may be effective in decreasing recurrences.
Alternatives to this therapy include either valacyclovir 1
gr bid or famciclovir 500 mg tid. Although long-term
antiviral treatment seems to reduce morbidity asso-
ciated with chronic HZO, there is no consensus on the
duration and the necessity of the maintenance therapy.
Miserocchi et al.54 reported that prophylactic oral anti-
viral therapy reduced the number of recurrences (stro-
mal keratitis and/or uveitis) from 3.4 to 2.1 per year in
patients with HZO.
Topical corticosteroids are necessary to control the
anterior segment inflammation. The dosage and dura-
tion of topical treatment should be decided on an
individual basis according to inflammatory activity.
The patients need close monitoring for safety and effi-
cacy. Topical corticosteroids should be tapered very
slowly over a period of 4 to 6 weeks. Tapering can
be challenging and often takes months to achieve.
Some patients may even require a long-term and
low-dose topical corticosteroid therapy in order to
maintain long term control of inflammation and pre-
vent recurrences. 11,46,51,54,55 Topical cycloplegics such
as cyclopentolate 1% bid should be given in all
patients in order to reduce pain and to prevent the
formation of posterior synechiae.
Elevated intraocular pressure is treated with topical
and oral antiglaucomatous drugs. Prostaglandin analo-
gues should probably be avoided since they may reacti-
vate the viral infection.57–59 Topical corticosteroids and
oral antiviral therapy may also help control the rise of
intraocular pressure with anti-inflammatory effects on
trabecular meshwork. With appropriate therapy, the
intraocular pressure is generally normalized within a
few days and antiglaucomatous therapy may be
discontinued.
When a surgical intervention such as cataract or
filtering surgery is planned, the eye should be quies-
cent and prophylactic oral antiviral therapy should be
given prior to surgery.
© 2017 Taylor & Francis Group, LLC
VZV Anterior Uveitis 5
VISUAL PROGNOSIS
In a prospective observational study of 73 adult
patients with HZO who received 7–14-day course of
systemic aciclovir treatment, only a mild to moderate
visual loss (visual acuity between 0.3 and 0.8) devel-
oped in 10% at 6 months of follow-up. Visual loss was
explained by optic nerve damage, corneal opacity or
exposure keratitis. None of the patients had AU at
6 months, even though AU was recorded in 44% at
1 week of follow-up.60 Kahloun et al.34 reported that
the final visual acuity was 20/40 or better in 78.4% of
eyes with HZO. Szeto et al.37 reported that epithelial
keratitis and stromal keratitis were independent risk
factors for visual loss and visual acuity was 6/12 or
less in 58.7% of their patients after resolution of HZO.
By contrast, moderate to severe visual loss was
reported in 9.4% of patients in a prospective longitu-
dinal study of HZO; and Hutchinson’s sign and AU
were found to be strong predictors of visual loss.61
Wensing et al.47 reported that 95% of eyes with HSV
or VZV AU had visual acuity better than 0.4 after
3 years of follow-up, which is similar to the results
reported by Tugal-Tutkun et al. 40 Even in cases of
VZV AU that presented with a rare occurrence of
severe hyphema and developed serious complications,
visual outcomes have been favorable after proper
treatment.41,42
PROPHYLAXIS
Varicella is a vaccine preventable disease. In the USA,
routine childhood vaccination was associated with 90%
decrease of varicella infection between 1995 and 2008.62
There are two concerns against universal vaccination
with the live-attenuated varicella vaccine virus. The
first is that suboptimal vaccination in a given popula-
tion may push forward the age of primary infection into
older population where the disease severity will be
much higher with frequent complications. The second
is based on the hypothesis that exogenous wild type
VZV exposure may boost immune response in seropo-
sitive persons and then protect against later reactivation
thus causing a decreased incidence of HZ, whereas
vaccination may hamper this effect.63 The vaccine
virus can establish latent infection and subsequently
reactivate causing HZ. Severe/disseminated HZ infec-
tion may develop months after vaccination in immuno-
compromised patients.64
Licensed zoster vaccine contains the same live-atte-
nuated strain of VZV used in varicella vaccines, but it
is much more potent. It is recommended in all persons
older than 60 years including those who report a pre-
vious episode of HZ and patients with chronic dis-
eases such as chronic renal failure, diabetes mellitus,
rheumatoid arthritis, and chronic lung disease.65 It is
 6 I. Tugal-Tutkun et al.
not necessary to ask patients about their history of
varicella or check varicella immunity.66 On the other
hand, zoster vaccination is not recommended for per-
sons who have previously received varicella vaccina-
tion. It is also contraindicated in immunocompromised
patients and those receiving 20 mg per day or higher
dose of systemic corticosteroids or TNF inhibitors.67
There are anecdotal reports of patients with HZO
developing recurrences 3 to 5 weeks after zoster vacci-
nation. 68,69 Thus, such patients may need to be fol-
lowed up to 6 weeks after vaccination.
CONCLUSIONS
Unilateral anterior uveitis associated with a typical
skin eruption of HZO or a history of HZO does not
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present a diagnostic challenge. In the absence of such
an association, VZV AU should be considered espe-
cially in older individuals who present with character-
istic features of unilateral viral AU, such as
granulomatous keratic precipitates, focal iris atrophy,
and ocular hypertension. A definitive diagnosis of
VZV AU can only be made by aqueous humor analy-
sis. The disease course may be uniphasic or chronic
relapsing. Patients have a favorable visual prognosis
following treatment with systemic antiviral agents and
topical corticosteroids.
DECLARATION OF INTEREST
The authors report no conflicts of interest. The authors
alone are responsible for the content and writing of the
article.
REFERENCES
1. Arvin AM. Varicella-zoster virus. Clin Microbiol Rev. 1996,
Jul;9(3):361–381.
2. Smith CK, Arvin AM. Varicella in the fetus and newborn.
Semin Fetal Neonatal Med. 2009;14(4):209–217.
3. Esmaeli-Gutstein B, Winkelman JZ. Uveitis associated with
varicella virus vaccine. Am J Ophthalmol. 1999;127(6):733–734.
4. Straus S, Ostrove JM, Inchauspé G, et al. NIH conference.
Varicella-zoster virus infections. Biology, natural history,
treatment, and prevention. Ann Intern Med. 1988;108
(2):221–237.
5. Thomas SL, Hall AJ. What does epidemiology tell us about
risk factors for herpes zoster? Lancet Infect Dis. 2004;4(1):26–33.
6. Cohen PR, Grossman ME. Clinical features of human
immunodeficiency virus-associated disseminated herpes
zoster virus infection –a review of the literature. Clin Exp
Dermatol. 1989;14(4):273–276.
7. Buchbinder SP, Katz MH, Hessol NA, et al. Herpes zoster
and human immunodeficiency virus infection. J Infect Dis.
1992;166(5):1153–1156.
8. Hilt DC, Bucholz D, Krumholz A, Weiss H, Wolinsky JS.
Herpes zoster ophthalmicus and delayed contralateral
hemiparesis caused by cerebral angiitis: diagnosis and man-
agement approaches. Ann Neurol. 1983;14(5):543–553.
9. Chapman RS, Cross KW, Fleming DM. The incidence of
shingles and its implications for vaccination policy.
Vaccine. 2003;21(19–20):2541–2547.
10. Tanaka Y, Harino S, Danjo S, Hara J, Yamanishi K,
Takahashi M. Skin test with varicella-zoster virus anti-
gen for ophthalmic herpes zoster. Am J Ophthalmol.
1984;98(1):7–10.
11. Cohen EJ. Management and Prevention of Herpes Zoster
Ocular Disease. Cornea. 2015;34(Suppl 10):S3–8.
12. Yawn BP, Gilden D. The global epidemiology of herpes
zoster. Neurology. 2013;81(10):928–930.
13. Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of
incidence and complications of herpes zoster: towards a
global perspective. BMJ Open. 2014;4(6):e004833.
14. Cohen EJ, Kessler J. Persistent dilemmas in zoster eye dis-
ease. Br J Ophthalmol. 2016;100(1):56–61.
15. Hope-Simpson RE. The Nature of Herpes Zoster: a Long-
term study and a new hypothesis. Proc R Soc Med.
1965;58:9–20.
16. Mahalingam R, Wellish M, Wolf W, et al. Latent varicella–
zoster viral DNA in human trigeminal and thoracic ganglia.
N Engl J Med. 1990;323(10):627–631.
17. Liesegang TJ. Herpes zoster ophthalmicus natural history,
risk factors, clinical presentation, and morbidity.
Ophthalmology. 2008;115(2 Suppl):S3–12.
18. Zaal MJ, Volker-Dieben HJ, D’Amaro J. Prognostic value of
Hutchinson’s sign in acute herpes zoster ophthalmicus.
Graefes Arch Clin Exp Ophthalmol. 2003;241(3):187–191.
19. Nakamura M, Tanabe M, Yamada Y, Azumi A. Zoster sine
herpete with bilateral ocular involvement. Am J Ophthalmol.
2000;129(6):809–810.
20. Borkar DS, Tham VM, Esterberg E, et al. Incidence of herpes
zoster ophthalmicus: results from the Pacific Ocular
Inflammation Study. Ophthalmology. 2013;120(3):451–456.
21. Jordan DR, Noel LP, Clarke WN. Ocular involvement in
varicella. Clin Pediatr (Phila). 1984;23(8):434–436.
22. Fernández De Castro LE, Sarraf OA, Hawthorne KM,
Solomon KD, Vroman DT. Ocular manifestations after pri-
mary varicella infection. Cornea. 2006;25(7):866–867.
23. Kandori M, Inoue T, Takamatsu F, Hori Y, Maeda N, Tano Y.
Two cases of varicella zoster virus keratitis with atypical exten-
sive pseudodendrites. Jpn J Ophthalmol. 2009;53(5):548–549.
24. Khan AO, Al-Assiri A, Wagoner MD. Ring corneal infiltrate
and progressive ring thinning following primary varicella
infection. J Pediatr Ophthalmol Strabismus. 2008;45(2):116–117.
25. Kachmer ML, Annable WL, DiMarco M. Iritis in children with
varicella. J Pediatr Ophthalmol Strabismus. 1990;27:221–222.
26. Sungur G, Hazirolan D, Duran S, Satana B, Arikan I,
Duman S. The effect of clinical severity and eyelid rash on
ocular involvement in primary varicella infection. Eur J
Ophthalmol. 2009;19(6):905–908.
27. Gargouri S, Khochtali S, Zina S, et al. Ocular involvement
associated with varicella in adults. J Ophthalmic Inflamm
Infect. 2016;6(1):47. doi:10.1186/s12348-016-0117-9.
28. Johnston NR. Red eye in chickenpox: varicella-related acute
anterior uveitis in a child. BMJ Case Rep. 2010;2010.
doi:10.1136/bcr.01.2010.2678.
29. Ostler HB, Thygeson P. The ocular manifestations of herpes
zoster, varicella, infectious mononucleosis, and cytomegalo-
virus disease. Surv Ophthalmol. 1976;21(2):148–159.
30. Shaw M, Handley SE, Porooshani H. A case of internal
ophthalmoplegia associated with varicella zoster. J Pediatr
Ophthalmol Strabismus. 2012;49:e44–7. doi:10.3928/
01913913-20120731-04.
31. Tappeiner C, Aebi C, Garweg JG. Retinitis and optic neuritis
in a child with chickenpox: case report and review of litera-
ture. Pediatr Infect Dis J. 2010;29(12):1150–1152.
32. Severson EA, Baratz KH, Hodge DO, Burke JP. Herpes
zoster ophthalmicus in Olmsted County, Minnesota: have
Ocular Immunology & Inflammation

systemic antivirals made a difference? Arch Ophthalmol.
2003;121(3):386–390.
33. Hoang-Xuan T, Buchi ER, Herbort CP, et al. Oral acyclovir
for herpes zoster ophthalmicus. Ophthalmology. 1992;99
(7):1062–1070.
34. Kahloun R, Attia S, Jelliti B, et al. Ocular involvement and
visual outcome of herpes zoster ophthalmicus: review of 45
patients from Tunisia, North Africa. J Ophthalmic Inflamm
Infect. 2014;4:25. doi:10.1186/s12348-014-0025-9.
35. Yawn BP, Wollan PC, St Sauver JL, Butterfield LC. Herpes
zoster eye complications: rates and trends. Mayo Clin Proc.
2013;88(6):562–570.
36. Tran KD, Falcone MM, Choi DS, et al. Epidemiology of
herpes zoster ophthalmicus: recurrence and chronicity.
Ophthalmology. 2016;123(7):1469–1475.
37. Szeto SK, Chan TC, Wong RL, Ng AL, Li EY, Jhanji V.
Prevalence of ocular manifestations and visual outcomes
in patients with herpes zoster ophthalmicus. Cornea.
2017;36(3):338–342.
38. Miserocchi E, Waheed NK, Dios E, et al. Visual outcome in
herpes simplex virus and varicella zoster virus uveitis: a
Downloaded by [Southern Cross University] at 22:48 13 October 2017
clinical evaluation and comparison. Ophthalmology. 2002;109
(8):1532–1537.
39. Thean JH, Hall AJ, Stawell RJ. Uveitis in herpes zoster
ophthalmicus. Clin Exp Ophthalmol. 2001;29(6):406–410.
40. Tugal-Tutkun I, Otük-Yasar B, Altinkurt E. Clinical features
and prognosis of herpetic anterior uveitis: a retrospective
study of 111 cases. Int Ophthalmol. 2010;30(5):559–565.
41. Hosogai M, Nakatani Y, Mimura K, Kishi S, Akiyama H.
Genetic analysis of varicella-zoster virus in the aqueous
humor in uveitis with severe hyphema. BMC Infect Dis.
2017;17(1):427. doi:10.1186/s12879-017-2518-2.
42. Okunuki Y, Sakai J, Kezuka T, Goto H. A case of herpes
zoster uveitis with severe hyphema. BMC Ophthalmol.
2014;14:74. doi:10.1186/1471-2415-14-74.
43. De Groot-Mijnes JD, Rothova A, Van Loon AM, et al.
Polymerase chain reaction and Goldmann-Witmer coeffi-
cient analysis are complimentary for the diagnosis of infec-
tious uveitis. Am J Ophthalmol. 2006;141(2):313–318.
44. Kido S, Sugita S, Horie S, et al. Association of varicella
zoster virus load in the aqueous humor with clinical
manifestations of anterior uveitis in herpes zoster
ophthalmicus and zoster sine herpete. Br J Ophthalmol.
2008;92(4):505–508.
45. Cimino L, Aldigeri R, Parmeggiani M, et al. Searching for
viral antibodies and genome in intraocular fluids of patients
with Fuchs uveitis and non-infectious uveitis. Graefes Arch
Clin Exp Ophthalmol. 2013;251(6):1607–1612.
46. Van Der Lelij A, Ooijman FM, Kijlstra A, Rothova A.
Anterior uveitis with sectoral iris atrophy in the absence of
keratitis: a distinct clinical entity among herpetic eye dis-
eases. Ophthalmology. 2000;107(6):1164–1170.
47. Wensing B, Relvas LM, Caspers LE, et al. Comparison of
rubella virus- and herpes virus-associated anterior uveitis:
clinical manifestations and visual prognosis. Ophthalmology.
2011;118(10):1905–1910.
48. Takase H, Kubono R, Terada Y, et al. Comparison of the
ocular characteristics of anterior uveitis caused by herpes
simplex virus, varicella-zoster virus, and cytomegalovirus.
Jpn J Ophthalmol. 2014;58(6):473–482.
49. Babu K, Kini R, Philips M, Subbakrishna DK. Clinical profile
of isolated viral anterior uveitis in a South Indian patient
population. Ocul Immunol Inflamm. 2014;22(5):356–359.
50. Harding SP, Porter SM. Oral acyclovir in herpes zoster
ophthalmicus. Curr Eye Res. 1991;10:Suppl:177–182.
© 2017 Taylor & Francis Group, LLC
VZV Anterior Uveitis 7
51. Cobo LM, Foulks G, Liesegang T, et al. Oral acyclovir in the
treatment of acute herpes zoster ophthalmicus.
Ophthalmology. 1986, Jun;93(6):763–770.
52. Tyring SK, Beutner KR, Tucker BA, Anderson WC, Crooks
RJ. Antiviral therapy for herpes zoster: randomized, con-
trolled clinical trial of valacyclovir and famciclovir therapy
in immunocompetent patients 50 years and older. Arch Fam
Med. 2000;9(9):863–869.
53. 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(8):1507–1511.
54. Miserocchi E, Fogliato G, Bianchi I, Bandello F, Modorati G.
Clinical features of ocular herpetic infection in an Italian
referral center. Cornea. 2014;33(6):565–570.
55. Pleyer U, Chee SP. Current aspects on the management of
viral uveitis in immunocompetent individuals. Clin
Ophthalmol. 2015;9:1017–1028.
56. Liesegang TJ. Corneal complications from herpes zoster
ophthalmicus. Ophthalmology. 1985;92(3):316–324.
57. Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes
simplex keratitis. Am J Ophthalmol. 1999;127(5):602–604.
58. Kroll DM, Schuman JS. Reactivation of herpes simplex virus
keratitis after initiating bimatoprost treatment for glau-
coma. Am J Ophthalmol. 2002;133(3):401–403.
59. Babu K, Murthy GJ. Cytomegalovirus anterior uveitis in
immunocompetent individuals following topical prosta-
glandin analogues. J Ophthalmic Inflamm Infect. 2013;3
(1):55. doi:10.1186/1869-5760-3-55.
60. Zaal MJ, Völker-Dieben HJ, D’Amaro J. Visual prognosis in
immunocompetent patients with herpes zoster ophthalmi-
cus. Acta Ophthalmol Scand. 2003;81(3):216–220.
61. Nithyanandam S, Stephen J, Joseph M, Dabir S. Factors
affecting visual outcome in herpes zoster ophthalmicus: a
prospective study. Clin Exp Ophthalmol. 2010;38(9):845–850.
62. Chaves SS, Lopez AS, Watson TL, et al. Varicella in infants
after implementation of the US varicella vaccination pro-
gram. Pediatrics. 2011;128(6):1071–1077.
63. Ogunjimi B, Van Damme P, Beutels P, Van Boven M.
Herpes zoster risk reduction through exposure to chicken-
pox patients: a systematic multidisciplinary review. PLoS
ONE. 2013;8:e66485. doi:10.1371/journal.pone.0066485.
64. Bhalla P, Forrest GN, Gershon M, et al. Disseminated, per-
sistent, and fatal infection due to the vaccine strain of var-
icella-zoster virus in an adult following stem cell
transplantation. Clin Infect Dis. 2015;60(7):1068–1074.
65. Hales CM, Harpaz R, Ortega-Sanchez I, Bialek SR; Centers
for Disease Control and Prevention (CDC). Update on
recommendations for use of herpes zoster vaccine. MMWR
Morb Mortal Wkly Rep. 2014;63(33):729–731.
66. Harpaz R, Ortega-Sanchez IR, Seward JF; Advisory
Committee on Immunization Practices (ACIP) Centers for
Disease Control and Prevention (CDC). Prevention of
herpes zoster: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR
Recomm Rep. 2008;57(RR–5):1–30.
67. Schmader KE, Levin MJ, Gnann JW Jr, et al. Efficacy, safety,
and tolerability of herpes zoster vaccine in persons aged
50-59 years. Clin Infect Dis. 2012;54(7):922–928.
68. Khalifa YM, Jacoby RM, Margolis TP. Exacerbation of zoster
interstitial keratitis after zoster vaccination in an adult. Arch
Ophthalmol. 2010;128(8):1079–1080.
69. Sham CW, Levinson RD. Uveitis exacerbation after vari-
cella-zoster vaccination in an adult. Arch Ophthalmol.
2012;130(6):793–794.