Cats with Runny Eyes. Treatment of Feline Herpes Virus Infections

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Israel Journal of Veterinary Medicine  Vol. 70 (4)  December 2015 11 Cats with Runny Eyes
Cats with Runny Eyes.
Treatment of Feline Herpes Virus Infections
Ofri, R.
Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Israel.
*
Corresponding Author: Prof. Ron Ofri, Department of Ophthalmology, Koret School of Veterinary Medicine, Hebrew University of Jerusalem,
P.O. Box 12 Rehovot, 761001, Israel. Phone: +972-3-9688589. E-mail: ron.ofri@mail.huji.ac.il
INTRODUCTION
Feline Herpes Virus (FeHV-1) is widespread in the domestic
feline population, especially in colonies and catteries. More
than 95% of the world’s cat population has been exposed
to the virus, and more than 80% are carriers (1, 2). Cats
are infected after direct or indirect contact with sick or car-
rier animals; the infection occurs through the oronasal and
conjunctival routes. Clinical signs of active disease include
conjunctivitis and keratitis with ulceration (early, superfcial
dendritic ulcers may stain with rose Bengal but not with
fuorescein) and possible upper respiratory signs. Stromal vas-
cularization and cellular infltration characterize the immune
response to viral particles in the cornea, either with or with-
out active viral replication. Secondary bacterial infections,
especially with Chlamydia felis and possibly with Mycoplasma
spp., are frequent, and symblepharon is a common sequel.
FeHV-1 may also play a role in the pathogenesis of corneal
sequestration and eosinophilic keratitis (1-3).
Cats that recover from the disease probably remain persis-
tent carriers due to latent infection in the trigeminal ganglia.
Te latent disease is characterized by the absence of clinical
signs, but viral shedding and reactivation can occur (1, 2).
Stressful events, such as an unrelated illness, the introduction
of a new pet or baby into the house, travel or fghting with
other animals, can serve as triggers of shedding and reactiva-
tion of latent infection. Treatment with corticosteroids can
have similar consequences. Te presence of a latent disease,
as well as the confounding impact of an overly-aggressive
immune response, presents great therapeutic challenges to the
practitioner. Drug availability, irritancy and dosing frequency
further complicate treatment of the disease.
PRINCIPLES OF TREATMENT
Antiviral medications are indicated in cats with active disease.
Te drugs are pyrimidine and purine nucleoside analogues
which interfere with the viral replication cycle, by inhibiting
target enzymes that incorporate nucleosides into nucleic
acids. Compiling results of multiple studies (4-8), in vitro
efcacy against FHV-1 is:
trifuridine> ganciclovir >idoxuridine>cidofovir>pencicl
ovir>vidarabine>valacyclovir> acyclovir
Importantly, antivirals are virostatic and are only efective
in treating actively replicating virus, achieving their efect by
interfering with viral DNA replication. Te drugs are not vi-
rucidal and therefore are unable to eradicate latent infection.
Signifcant toxicity can occur with antiviral administration,
due to the intracellular location of the virus and the inability
of available medications to selectively target viral, rather than
host cell, replication.
Virostatic drugs usually have to be administered fre-
quently, and treatment is often continued for 10-14 days
after remission of clinical signs. Furthermore, as the drugs
are not virucidal, owners should be warned of the possibility
of shedding, reactivation and recrudescent infection (9).
Tere are two iatrogenic factors that may induce recru-
descent FeHV-1 infection. One is corticosteroid treatment.
Corticosteroids are contraindicated in all cases of primary
ocular FeHV-1infection, because they will exacerbate ac-
tive viral infection; thus, due to corticosteroid treatment a
self-limiting conjunctivitis may become a chronic corneal
infection. Terefore, any corticosteroid treatment in cats must
be carefully considered, as most cats should be suspected of
being potential FeHV-1 carriers. When such treatment is
Israel Journal of Veterinary Medicine  Vol. 70 (4)  December 2015 Ofri, R. 12
unavoidable (e.g. in cases of eosinophilic keratitis) it should
probably be combined with concurrent anti-viral therapy. In
this context it is important to note that because the FeHV-1
may be reactivated due to immunosuppression, the prognosis
for the diseases is poor in immunosuppressed patients (i.e.
FeLV- or FIV-infected) because the recurrence rate can be
high (1-3).
Another factor which may induce viral shedding and
reactivation is stress, and events such as the introduction of
a new animal to the household or traveling to cat shows may
exacerbate the symptoms. Similarly, frequent treatment with
multiple drugs may sometimes aggravate the clinical signs
of the disease. If worsening of signs is noted, the clinician
is advised to carefully consider reducing (or even ceasing)
treatment rather than increasing it.
Topical antiviral medications
Trifuridine 1% (Viroptic®), idoxuridine 0.1% (Stoxil®)
and vidarabine 3% (Vira-A®) are variably efective against
FeHV-1, with trifuridine having the highest efcacy as well
as transcorneal penetration (4-6). However, trifuridine also
tends to be more irritating to cats, and in fact sometimes
induces hyperemia of the eyelids and conjunctiva that may
mimic worsening of the disease. In such cases, other drugs
should be considered. Furthermore, the drug requires frequent
administration (5-6 times/day), which can increase stress and
decrease compliance (6, 10). Idoxuridine and vidarabine are
less irritating and are administered less frequently, but are
difcult to obtain because they are not widely available com-
mercially, although they may be ordered from compounding
pharmacies (9).
Newer recommendations for topical antiviral administra-
tion in cats include cidofovir 0.5% (7, 11, 12). Cidofovir,
which is not commercially available as an ophthalmic prepa-
ration, has strong in vitro and in vivo efcacy against FeHV-1
infection, with treatment reducing severity of clinical signs
and viral shedding. Importantly, cidofovir’s benefcial efect
has been demonstrated with twice daily administration, a
signifcant advantage compared to other topical antiviral
medications. Cidofovir is less toxic than other antivirals due
to its relatively high specifcity for viral, rather than host,
replication proteins. However long-term safety studies have
yet to be published; indeed, cidofovir has been associated with
a dose-dependent nephrotoxicity in humans and cat owners
should be warned to protect themselves from exposure to
cidofovir solutions. Ganciclovir (Zirgan®) is commercially
available as a 0.15% ophthalmic gel and has in vitro efcacy
against FeHV-1, but has not been studied in clinical feline
patients and may be toxic (5, 8). Even if found efective and
non-toxic, it is not likely to be of any value in treating FeHV-
1 in cats due to its high cost.
Antiviral therapy with acyclovir (Zovirax®) or valacyclo-
vir, a prodrug of acyclovir, is the drug of choice for treating
ophthalmic herpes disease in humans, but neither drug ap-
pears to suppress FeHV-1 replication. In fact, both drugs
are contraindicated in cats as acyclovir is myelosuppressive
in this species, and valacyclovir is extremely toxic and often
fatal to cats (13-15).
Oral antiviral medications
Famciclovir, a prodrug of penciclovir, is a very safe and efec-
tive oral drug for the treatment of FeHV-1 (16-22). Due to
complex pharmacokinetics of famciclovir and penciclovir
in cats, and the variable target penciclovir concentrations
needed to produce a clinical efect, the accurate oral dose
is currently not defnitively known. In clinical studies, oral
administration of 90 mg/kg famciclovir three times daily
for 3 weeks to cats with experimentally-induced FeHV-1
disease improved outcomes for systemic, ophthalmic, clini-
copathologic, virologic, and histologic variables and reduced
viral shedding. In naturally-infected cats, 62.5 mg orally once
daily for 7 days then twice daily was reported to result in
clinical improvement. However, a single dose of 125 mg or
500 mg famciclovir, administered at the time of admission
to a shelter, did not lessen clinical signs or viral shedding in
cats, even in the presence of appropriate plasma penciclovir
levels (16-22).
Additional therapies
It has been suggested that recurrent infection may be mini-
mized by oral lysine supplementation (23-25). It is hypoth-
esized that lysine can be helpful in the treatment of FeHV-1
infection because viral growth appears to be inhibited by
high intracellular concentrations of lysine and low levels of
arginine. Tus, long-term treatment (250-500 mg PO twice
daily) may decrease shedding, viral replication, and severity
of conjunctivitis, and may be used for long-term maintenance
therapy. However, results of clinical investigations are equivo-
cal, perhaps due to the high levels of dietary arginine in cats.
Te efcacy of lysine to prevent herpes simplex in humans
Review Articles
Israel Journal of Veterinary Medicine  Vol. 70 (4)  December 2015 13 Cats with Runny Eyes
is associated with severely arginine-restricted diets. Tis is
not possible with obligate carnivore patients, and the higher
arginine content of feline diets may continue to hinder the
success of lysine prophylaxis of FeHV-1 (23-26).
Interferons are components of the innate immune system
that induce expression of antiviral proteins within host cells,
thus creating an antiviral environment, and also exert im-
munomodulatory efects that further limit the impact of viral
infections (26-30). Recombinant human IFN-α and feline
IFN-ω have been evaluated relative to anti-FeHV-1 efect,
with the feline version demonstrating greater in vitro efcacy.
Te drug can be given as low oral doses (25 units/day) or eye
drops (10
3
to 10
6
units/ml) applied 2 to 3 times daily, and
has decreased the severity of clinical signs in experimentally-
infected cats. However, results of clinical feld studies have
been disappointing, possibly due to the timing of administra-
tion relative to infection and shedding, as well as uncertainty
surrounding appropriate dosing protocols and handling of
IFN preparations (27-31).
Supportive therapy may include tear replacements, topical
antibiotics and debridement of necrotic corneal epithelium
with a cotton-tipped swab to remove viral particles.Topical
tetracycline is frequently added because coinfections with
Mycoplasma spp. or Chlamydia felis are common. Eyes that
are irritated by topical tetracycline may be treated with cip-
rofoxacin. In cases of respiratory diseases, oral azithromycine
or doxycycline should be considered (2, 9).
ACKNOWLEDGEMENTS
Te author thanks: A. Clode, A. Regnier and G. Davidson
for their input on the topic during the 2015 annual meeting
of the European College of Veterinary Ophthalmologists,
Helsinki, Finland.
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