APAOSydney 2011

Herpetic Eye Disease

Mei-Ling Tay-Kearney
Lions Eye Institute
Perth
Western Australia
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Virology

 About 100 different herpesviruses have been described, 8 found in

humans
 Linear double-stranded DNA, surrounded by an icosahedral capsid
of 162 capsomeres, an amorphous tegument and an envelope
 The lipid envelope is studded with glycoprotein spikes (peptomers),
these recognise receptors on the host cell membrane facilitating
viral entry into cell
 These peptomers are particularly antigenic, forming primary
targets for both humoral and cell-mediated immunity
 Only enveloped virions are infectious, infectivity easily destroyed
by physical or chemical agents
 All establish latency after primary infection, the viral genome
existing as closed loops with only a small number of viral proteins
expressed
 The herpesviridae family is divided into 3 subfamilies according to
cell tropism, reproduction rate and host range
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Viruses of Humans Common name Subfamily

Human herpesvirus 1 Herpes simplex type 1 alpha
Human herpesvirus 2 Herpes simplex type 2 alpha
Human herpesvirus 3 Varicella-zoster alpha
Human herpesvirus 4 Epstein-Barr gamma
Human herpesvirus 5 Cytomegalovirus beta
Human herpesvirus 6/7 Exanthum subitum beta
Roseola infantum
Human herpesvirus 8 Kaposi‟s sarcoma gamma

Ocular HSV disease

HSV is probably the most common infective cause of visual impairment in
developed nations, largely as a result of its recurrent nature. About 400
000 people in the USA have ocular HSV disease with 50 000 new and
recurrent episodes annually. Asymptomatic viral shedding is an important
source of transmission. HSV-1 is highly prevalent, with 60%-70% of
children by age 5 years seropositive for HSV increasing to 90% in
adulthood. Despite the widespread prevalence, only 20%-30% manifest
clinical disease and ocular disease is seen in less than 1%.

Most studies of HSV ocular disease were conducted many years ago, or
have looked at selected populations only.
Two studies however have provided helpful data on the incidence of
different presentations of ocular HSV.1,2

Primary ocular HSV disease

Study Moorfields Eye Rochester Study
Hospital
Year of study 1973-1980 1950-1982
Patients 108 122
Mean age (yrs) 35 37
M:F 1:1 1:1
Conjunctivitis (%) 84 25
Blepharitis (%) 38 46
Epithelial keratitis (%) 15 63
Stromal keratitis (%) 2 6
Uveitis (%) Not done 4
Unilateral disease (%) 81 88
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The Moorfields data may be more representative of the clinical picture

because of the prospective data collection and a higher suspicion for HSV
infection. The most common presentation of a primary infection appears
to be blepharoconjunctivitis, though only 1%-6% of primary infections
manifest clinically. Therefore, most presentations of ocular HSV are
reactivations.

Recurrent ocular HSV

 recurrences occur in over a third of patients, and more than half
of these will have more than 1 episode
 recurrences of any form of ocular disease increase with time; 10%
at 1 year, 23% at 2 years, 36% at 5 years and 63% by 20 years
after the primary episode (Liesegang et al)3
 most common form appears to be either blepharitis or HSV
epithelial keratitis

Risk factors for HSV epithelial and stromal keratitis

 largely ill-defined
 in the Herpetic Eye Disease Study (HEDS),4 326 patients were
followed for 18 months, the risk of a recurrence of HSV epithelial
keratitis was not significantly affected by a previous episode of
epithelial keratitis. But a previous episode of stromal keratitis
increased the risk of a subsequent one 10 fold (P < 0.001)
 age, gender, race and non-ocular herpes were not risk factors in
HEDS,

Bilateral ocular HSV

 frequency varies, 3%-19%
 more frequent in persons with atopic disease, men and younger
patients

Ocular HSV in children

 tends to be more severe with a higher incidence of dendritic ulcers
 31 eyes of 28 children in Dublin documented higher incidences of
astigmatism (78%), visual impairment (89%), and recurrences (87%)
than would be expected in adults5

Ocular HSV in Immunocompromised patients

 recurrent HSV keratitis are more frequent
 presentation may be atypical in transplant patients – marginal
multiple dendrites with subepithelial infiltrates in uninflamed eyes
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Pathogenesis

 the major route of ocular infection is zosteriform, with a 2-step

process of infection and reactivation
 the optic nerve, trochlear, oculomotor and trigeminal nerves are
important routes of transmission of virus into the eye
 different strains may dictate type of disease and recurrence rates
 infection with different strains possible, making vaccinations
difficult
 the ocular disease seen is due to a combination of a direct viral
cytopathic destruction with different degrees of
immunopathogenic involvement

Latency
 some studies suggest that HSV can establish latency at peripheral
sites
 in one PCR study of corneas from 110 patients (52 with known HSK
and 58 with non-herpetic corneal disease), HSV-1 DNA was
detected in 82% of patients with HSK and in 22% in patients
without HSK6
 D Kennedy et al reviews this issue in Cornea 2011,30:251-259.
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Classification

1. Infectious epithelial keratitis

- vesicles
- dendritic ulcer
- geographic ulcer
- marginal ulcer
2. Neurotrophic
3. Stomal keratitis
- necrotizing
- immune
4. Endotheliitis
- disciform
- diffuse
- linear

Manifestations
 corneal vesicles earliest manifestations, these may be mistaken for
PEE
 within 24 hrs, these vesicles coalesce to form dendritic or
geographical ulcers
 the dendritic ulcer is a branching linear lesion with terminal
endbulbs, swollen borders containing live virus
 it is a true ulcer extending beyond the basement membrane,
therefore staining positive for fluorescein, and Rose Bengal at the
borders
 geographical ulcers are enlarged dendritic ulcers with swollen,
scalloped epithelial borders, unlike neurotrophic ulcers with smooth
borders
 geographical ulcers may be associated with longer healing time of
dendritic ulcers and prior topical steroid use (Wilhelmus)7
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Dendritic ulcers

Marginal ulcer

 marginal ulcers are uncommon, tend to be more symptomatic, with

an anterior stromal infiltrate, and accompanying blood vessels
 it can be more difficult to treat and most often confused with
staphylococcal marginal keratitis
 an epithelial defect is always present with an HSV marginal ulcer,
often associated with neovascularisation, progression is central,
can occur in any meridian and blepharitis is not prominent
 a staphylococcal marginal infiltrate does not have an epithelial
defect, new vessels are not seen, progression is circumferential,
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blepharitis is prominent and typically occurs at the 2,4,8,10 o‟clock

meridians

Neurotrophic keratopathy
 corneal sensation is impaired, with decreased tear production
 may be exacerbated by chronic use of topical medications
 irregularity of corneal surface, lack of corneal lustre, punctate
erosions are early signs
 stop all unnecessary topical medications, use preserve-free
ocular lubricants
 in severe cases, gentle debridement of rolled epithelial borders
may be beneficial
 also consider tarsorraphy, botox-induced ptosis,
 improve ocular surface milieu with lid scrubs, massage, oral
tetracyclines, vitamin C
 autologous serum eye drops are very useful

Neurotrophic ulcers

Stromal disease

Whilst stromal disease accounts for 2% of primary disease, it is

responsible for 20%-48% of recurrent episodes.

 primary stromal involvement may be from direct viral invasion

(necrotizing), or as a result of the host‟s immune reaction to viral
antigens within the stroma (interstitial keratitis)
 necrotizing stromal keratitis is uncommon, and may resemble
bacterial/fungal keratitis
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 necrosis, ulceration and a dense stromal infiltration with an

overlying epithelial defect is seen
 corneal thinning and perforation can occur in a short period of time
 on the other hand, immune stromal keratitis is common, accounting
fore 20% of patients with ocular HSV
 an antigen-antibody-complement(AAC) cascade in response to viral
antigens within stroma results in intrastromal inflammation
 subepithelial haze, punctate stromal opacities, immune ring,
neovascularization and lipid keratopathy may be seen

Stromal keratitis with neovacularisation

Stromal keratitis with perforation Stromal disease with lipid keratopathy

Stromal disease with scarring

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Endotheliitis

Corneal stromal edema without stromal infiltrates, classified according to

the distribution of the KPs and configuration of the overlying edema.

 KPs, overlying stromal and epithelial edema, anterior uveitis are

characteristic
 in some cases, the KPs are not seen till the severe corneal edema
resolve
 probably an immune reaction directed against the corneal
endothelial cells which may contain viral antigens
 disciform endotheliitis is the most common with patients
complaining of ocular discomfort, photophobia and limbal injection
is not uncommon
 unlike disciform and diffuse forms, linear endotheliitis is difficult
to treat, therefore use of oral antivirals should be considered

Disciform endotheliitis with KPs

Diffuse endotheliitis
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Disciform endotheliitis

Treatment

1. Avoidance of trigger factors

2. Aciclovir (ACV)

- readily penetrates the cornea after topical application, and

achieves therapeutic concentrations in aqueous
- 5 doses of 400mg ACV orally taken 24 hours before cataract
surgery reached levels above ED50 range for HSV-1 (mean
3.26M)
- oral ACV may be a useful adjuct in children who tend to have
a more severe clinical course (12-80mg/kg/day)
- oral ACV should be given to patients with high rates of HSV
stromal keratitis recurrences, rates reduced by half in
patients given 400 mg bd ACV compared to placebo (HEDS)
- similar prophylaxis applied to children with recurrent HSV
stromal keratitis (10-20mg/kg/day)
- there is no consensus as to which patients should receive
prophylaxis and for how long, but patients with atopy, HIV
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infection and other forms of immunosuppression are good

candidates
- prophylaxis for epithelial keratitis, blepharoconjunctivitis is
less clear

3. Topical steroids

- when a decision is made to use steroids, a significant

strength and frequency should be used to suppress the
inflammation
- customise dose according to level of inflammation
- avoid rapid tapering or abrupt cessation of drops to prevent
“rebound” inflammation
- concept of the „threshold‟ or „flare‟ dose – some patients may
need steroids long term used at a frequency above their
threshold dose
- cover with topical antivirals – „drop for drop‟ , this may be
discontinued when a weak steroid eg prednisolone phosphate
0.1% is used once a day.

Corneal grafts and HSK

 replication of HSV –1 accounts for early recurrences of HSV

keratitis after corneal grafts
 there is a 10%-25% recurrence rate in the first year of follow-up
in patients on topical steroids and antiviral therapy
 the higher recurrence rates in the first year may be due in part to
the more frequent use of topical steroids
 HSV disease should be considered as a possible cause of graft
failure
 HSV DNA have been detected in donor tissue of patients without a
history of ocular HSV8
 graft-to host transmission of HSV is a rare event, but can have
serious ocular sequelae
 in a retrospective analysis of 2398 PKPs performed between 1980
and 1995, 18 presented with HSV epithelial keratitis in their grafts
i.e. an incidence of 1.2/1000 person-years9
 most cases of infections occur within 2 years of PKP
 donor tissue is not routinely screened for HSV
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 prophylactic oral antivirals should be used in patients with known

HSV keratitis and continued for at least a year after
transplantation10

Failed grafts

Excimer laser photoablation and ocular herpes

 case reports in humans and animal studies suggest that HSV can be
re-activated by excimer laser keratectomy
 prophylaxis with valaciclovir reduced viral shedding in animal
studies
 at present, photoablation of corneas with herpes are discouraged
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Herpetic Anterior Uveitis

Herpetic anterior uveitis (HSV or VZV ) probably accounts for 5%-10% of

all uveitis cases seen at tertiary referral centers and which makes this
entity the most common cause of infectious anterior uveitis in developed
countries.

 may or may not have a history of previous ocular HSV/VZV

(herpes sine herpete)
 it is almost always unilateral
 acute onset with pain, redness, photophobia and blurring of
vision
 if severe, hypopyon and /or hemorrhage may be seen
 if occurs with stromal keratitis or endotheliitis, anterior uveitis
is mild
 KPs may be small, large or stellate,
 patchy iris pigment epithelial loss, pupil is mid-dilated,
unreactive, distorted, best seen on transillumination
 IOP typically raised, presumed secondary to trabeculitis
 corneal sensation often decreased
 intact viral particles have been isolated in aqueous with
lymphocytic infiltration in iris stroma
 in VZV uveitis, perineuritis and perivasculitis found with
vasoocclusive disease responsible for sectorial iris atrophy
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Management

 combination of topical steroids and oral antivirals often required,

particularly in patients with numerous recurrences11
 topical steroids must be tapered slowly and for some patients, left
on low dose maintenance therapy
 oral antiviral prophylaxis( eg 400mg bd acyclovir) is useful in
patients with tendency to flare when off medications
 ocular hypotensives may be necessary in the acute stages when IOP
is high. Note latanaprost may cause reactivation of HSV
 Always examine the posterior segment to exclude ocular
involvement as arteriolar sheathing only has been described12

Herpetic Retinitis
More commonly known as acute retinal necrosis (ARN), the clinical picture
was only described in 1971 by Urayama et al. ARN has a two-peak age
distribution, the first peaking at 20 years and the second at 50 years of
age. HSV is presumed responsible for the first peak and VZV the second.
CMV have been reported in rare cases.
Herpetic retinitis is also seen in certain clinical settings eg congenital
zoster, chickenpox in adulthood and in patients with HSV encephalitis.
ARN may affect individuals who are immunocompetent or
immunosuppressed.

Clinical features

 classic symptoms & signs do not always occur in practice

 best to regard all entities as herpetic retinitis, the clinical picture
modified by the immune status of the patient
 retinal vasculitis (arteritis), disc edema and macula ischemia with a
„cherry redspot‟ may be seen
 retinal lesions secondary to HSV/VZV tend to start in the far
periphery with „satellite‟ lesions along the posterior border
 as retinal lesions regress and heal, vitreous inflammation and haze
intensifies, this is an immune response to dying retina and not due
to a viral cytopathologic effect
 retinal detachment occurs in 75% of cases
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 in patients with severe immunosuppression as seen in AIDS, the

retinal lesions occur in the outer retina sparing the retinal vessels,
with little vitreous reaction (PORN)
 treatment with acyclovir reduces infection of fellow eye from 70%
to 13% in the first year13

Herpes retinitis

VZV HSV

CMV VZV
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PORN

Management

 intravitreal injections of foscarnet (1200mcg/0.1ml) as

effective for HSV, VZV and CMV
 intravenous acyclovir 10-15mg/kg tds for 10 - 14 days, followed
by high dose oral antivirals for at least 6 weeks
 topical and oral prednisolone (1mg/kg)
 barrier laser, early vitrectomy
 silicone oil for retinal detachments
 if unsure of diagnosis or if lesions worsen despite treatment,
biopsy

CMV Retinitis

Most commonly seen in patients who are immune suppressed. Since the
introduction of highly active anti-retroviral therapy (HAART) in late
1996, the incidence of this opportunistic infection has dropped
dramatically. CMV retinitis is now more commonly seen in post-transplant
patients, those on immunosuppressive drugs and in HIV patients who have
failed or have no access to HAART.

 lesions may be hemorrhagic and swollen in the posterior pole,

granular in the periphery or may resemble frosted-branch angiitis
 complications include retinal detachments, silicone oil cataracts and
immune recovery phenomena
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CMV retinitis

ARN and CMV retinitis

CMV retinal detachment

Silicone oil

Management
 immune restoration with HAART
if possible
 intravitreal injections, systemic
ganciclovir or foscarnet
 GCV implant
 oral ganciclovir
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Concept of immune restoration disease (IRD)

 First described in patients with AIDS treated with HAART

 there is initially a polyclonal expansion of memory CD4+ T-cell
numbers in conjunction with an increase of the T-receptor
repertoire, followed by an increase of naïve CD4 T-cells
 improvement of T-cell function follows
 immune restoration typically occurs 2-3 months after HAART
 host response to infective antigens in tissues results in „relapses‟ in
conjunction with iritis, vitritis, macula edema which may lead to
epiretinal membrane formation and tractional retinal detachment
 treatment includes anti-infective agents as well as anti-
inflammatory drugs ( usually steroids)
 HLA linkage found for immune restoration to CMV

Herpes Zoster Ophthalmicus

 Lifetime risk is 10-30%

 2/1000 age 20; 10/1000 age 80+
 Second only to thoracic zoster
 V-1 20 times more involved
 50-70% suffer some form of visual morbidity
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Risk Factors
 decreased cell mediated immunity to VZV
- age (immunosenescence)
- iatrogenic immunosuppression
- HIV
- haematological cancers

 if immunocompromised
- 12-25X prevalence
- tends to be more severe and prolonged
- dissemination
- iv treatment required

In children
 uncommon in children < 12 yrs (1%)
 greatest risk of HZO if child had varicella age 12 months or less
 usually mild, much less post-herpetic neuralgia
 can occur after zoster vaccination
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Mechanisms of complications
 direct viral infection
 vasoocclusive vasculitis
 immune reaction
 neuropathic cornea

Ocular complications
 most occur within the month of rash onset
 corneal ( 60%) and anterior uveitis14 ( 40%) most common
 ocular hypertension usually seen with anterior uveitis
 epi/scleritis
 retinitis
 nerve palsies
 others

Postherpetic neuralgia
 seen in about 15% of cases of HZO
 incidence increases with age, duration of acute pain & severity
of rash
 use of amitriptyline advocated to reduce acute pain
 topical capsaicin, lignocaine, ketamine also used with variable
success
 gabapentin, 300-900 mg po tds for severe cases
 Condi‟s crystals, 10% iodine topically for weeping skin lesions
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Do oral antivirals make a difference

 found to decrease duration of acute pain
 viral shedding decreased
 time to crusting of skin lesions increased
 there is a reduction of the severity of ocular complications ( Cobo
et al,15 Harding16, Herbort17 )
 reduction in neurotrophic keratitis ( Severson18 )
 severity of ocular complications increase with delay of treatment
(Severson )

Varicella Vaccine19,20
 live attenuated Oka strain ( Varilix, Varivax)
 single dose for infants, booster required for individuals 13 yrs and
older
 zoster can still occur but is a milder disease
 as exposure to varicella reduces the risk of zoster, consider
vaccination on individuals older than 60 yrs

Antiviral agents

Compounds with antiviral activity against the herpes viruses and mode of
administration:

Acyclic guanosine nucleoside thymidine kinase dependant DNA polymerase

inhibitors
Aciclovir topical, oral, intravenous intravitreal
Valaciclovir oral prodrug of aciclovir
Ganciclovir topical, oral, intravenous, intravitreal
Valganciclovir oral prodrug of ganciclovir
Penciclovir topical, intravenous
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Famciclovir oral prodrug of penciclovir

Direct nucleoside DNA polymerase inhibitors

Cidofovir intravenous, intravitreal
Foscarnet topical, oral, intravenous, intravitreal inorganic
pyrophosphate analogue

Antisense Oligonucleotide DNA chain terminator

Fomivirsen intravitreal antisense oligonucleotide prevents DNA
chain elongation

Other

Trifluridine topical fluorinated pyrimidine nucleoside inhibits viral

DNA synthesis. More effective than idoxuridine and equivalent to
vidarabine. May be useful in aciclovir resistance. Trifluridine
resistance and hypersensitivity can occur
Idoxuridine topical iodinated thymidine analogue interferes with
various viral enzymes. Resistance is common
Vidarabine topical and previously intravenous adenine nucleoside
inhibits viral DNA synthesis
Docosanol topical long chain alcohol inhibits viral assembly and cell
entry
Brivudine - not yet available in Australia

The very first antiviral drug, idoxuridine, became available in 1963. In

1977 vidarabine , the first topical and parenterally administered anti-
herpes-viral agent was released. The introduction of acyclovir in 1988
marked a major breakthrough because of its high efficacy and low
toxicity which will be discussed further. The landmark Herpes Eye
Disease Study provided evidence for the effectiveness of prophylactic
treatment with oral acyclovir in reducing the recurrence of epithelial
disease. The study‟s approach to stromal disease was flawed in not
separating necrotic from interstitial / endotheliitis related stromal
disease. However results suggested that there probably is a benefit to
acute and prophylactic use of oral aciclovir in stromal necrotic disease.
Insufficient numbers were recruited to determine the benefit of
treatment for herpetic uveitis. Again the trend was towards
effectiveness of oral antiviral treatment and it is our experience that
this is definitely helpful, particularly in more severe cases.
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Therapy for HSV and VZV:

Acyclic guanine nucleoside analogues: Aciclovir / Valaciclovir,
Penciclovir / Famciclovir
These agents are phosphorylated intracellularly by viral kinase to
become active inhibitors of viral DNA synthesis. The active
nucleoside triphosphate is present in 40-100 fold increased
concentrations in virally infected cells compared with non-infected
cells. It has minimal effects on cellular function of non-infected
mammalian cells. Valaciclovir is converted rapidly to aciclovir by
first pass hepatic and intestinal enzymatic hydrolysis. Famciclovir is
converted to penciclovir following intestinal absorbtion. Penciclovir
is 100 fold more potent against viral DNA polymerase than aciclovir
and is present in cells for longer and in higher concentrations. The
prodrugs valaciclovir and famciclovir have higher bioavailability than
their active metabolites, aciclovir and penciclovir. Because of these
features famciclovir and valacyclovir are administered at lower
systemic doses than aciclovir and are less toxic. Similar
concentrations of these drugs are found in all body fluids including
aqueous, CSF, breast milk and fetal circulation. They are excreted
mainly through the kidneys. Side effects are rare but include
nausea, reversible nephrotoxicity, neurotoxicity, diarrhoea and
headache. (famciclovir may be mutagenic and decrease
spermatogenesis). Aciclovir is not thought to be teratogenic. Drug
interactions are few. Mycophenolate Mofetil potentiates the
effects of aciclovir by depleting deoxyguanosine (for which aciclovir
triphosphate competes). Famciclovir and penciclovir have no known
drug interactions. Bioavailability of aciclovir is 10-30% compared
with its prodrug, valaciclovir’s bioavailability of 70%. Bioavailability
of penciclovir is 5% compared with 65-77% for its prodrug
famciclovir.

:
HSV1 : HSV2 : VZV / EBV = 1 : 0.5 : 0.1. It has little activity against
CMV or HHV6
Although aciclovir is ineffective in established CMV it may be used for
prophylaxis. It does not have any clinical effect in infectious
mononucleosis but may help with EBV related oral hairy leucoplakia

Dosages:
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HSV VZV Necrotising retinitis Prophylaxis

Aciclovir 400mg 5x/d 800mg 5x/d 500mg/m2IV 400mg bd

or 10-15 mg/kg tds
for 10-14d, then
600mg 5x/d for
6-12 w
Valaciclovir 500mg tds 1000mg tds 500mg bd

Famciclovir 250mg tds 500mg tds 250mg bd

In VZO acyclovir 800mg 5x/d for 7d reduces pain, healing time, keratitis
& uveitis if given within 72h
Valaciclovir 1000mg tds for 7d provides faster pain relief than aciclovir
in adults >50years old
Ganciclovir gel is effective for HSV keratitis.

HSV Resistance occurs by the following mechanisms in order of

importance:
1. Absence / partial production of viral thymidine kinase
2. Altered thymidine kinase substrate specificity
3. Altered viral DNA polymerase
VZV resistance occurs by the following mechanisms in order of
importance:
1. Decreased thymidine kinase activity
2. Rarely DNA polymerase resistance

Resistance is defined as in vitro inhibitory concentrations > 2-3 μg/ml

which predicts failure of therapy in immunocompromised patients.
Resistant viruses exist in normal wild virus isolates
Intravenous foscarnet is usually effective in progressive aciclovir
resistant disease
Ganciclovir may be ineffective against thymidine kinase deficient HSV.

Therapy for CMV:

Ganciclovir
This drug undergoes intracellular phosphorylation by viral UL97 gene
encoded phosphotransferase following which it inhibits viral DNA
polymerase. Ganciclovir’s bioavailability is 6-9% compared with its
prodrug, valganciclovir, at 61%. Valgangiclovir bioavailability increases if
taken with food. Excretion is predominantly renal. Side effects include
 26

myelosuppression, GIT & CNS toxicity as well as teratogenesis. Oral

ganiclovir 1000mg tds in addition to intravitreal treatment reduces time
to progression of CMV retinitis
Resistance is conferred by impaired phosphorylation or DNA polymerase
mutation. These strains may be cross resistant to foscarnet and
cidofovir.
Dose: Ganciclovir IV induction5mg/kg bd x 2-3/52 then 5mg/kg daily or
6mg/kg 5d/wk or ganciclovir 1000mg po tds, or valganciclovir 900mg po
bd WITH ganciclovir 2mg/0.1ml intravitreal weekly

Cidofovir ( not used much now)

This drug has 8-600 fold greater activity on viral than human DNA
polymerase. It is phosphorylated to its active form by cellular rather
than viral enzymes and is hence effective against resistant viruses with
thymidine kinase mutation induced resistance and UL97 mutations but not
those with DNA polymerase mutation induced resistance. Prior ganciclovir
treatment may lead to cidofovir resistance. Cidofovir is administered
intravenously with probenecid. It is excreted by the kidneys and is
nephrotoxic, teratogenic and possibly carcinogenic. Uveitis and hypotony
are common ocular side effects.
Dose: Induction 5mg/kg IV weekly x 3 wks then 3-5mg/kg biweekly.
Intravitreal 20ug every 5-6wk
Foscarnet
Because foscarnet‟s effect is on DNA polymerase it is useful for
resistant strains with thymidine kinase mutations. Viral resistance may
occur through DNA polymerase mutation
Side effects include renal impairment, neurotoxicity, GIT upset,
neutropaenia, anaemia and hypocalcaemia.
Dose: Induction: 90mg/kg bd x 2wk then 120mg/kg IV daily. Intravitreal
1200ug in 0.1ml weekly
Fomivirsen ( not used much now)
Although in principle fomivirsen’s function as an antisense oligonucleotide
is of benefit in the treatment of viruses with common mechanisms of
resistance its side effects severely limit its usefulness. These include
uveitis, vitritis, cataracts and IOP rise. Prior cidofovir treatment worsens
uveitis.
Dose: 330ug on day 1 & day 15, then monthly.
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