INFECTIOUS DISEASE AND THE EYE 0195--5616/00 $15.00 + .

00

CANINE VIRAL INFECTIONS

A. Michelle Willis, DVM

INFECTIOUS CANINE HEPATITIS

Infectious canine hepatitis is a multisystemic viral disease of dogs caused

by canine adenovirus type 1 (CAV-1). In addition to disease caused by natural
infection, vaccination with modified live virus (MLV) vaccines can produce
interstitial nephritis3 and ocular disease18• 52 in dogs.

Transmission

Canine adenovirus type 1 has been isolated from all body tissues and
excretions. 25 The virus is environmentally stable and resistant to disinfection.
Infectious canine hepatitis is highly contagious. The virus is transmitted by
contact with infected animals, contaminated fomites, and ectoparasites. Dogs
and foxes serve as reservoirs for CAV-1, which can be shed in the urine of an
infected animal for 6 to 9 months.

Pathogenesis

Following oronasal exposure, virus localizes in the tonsils, and viremia

subsequently develops. The principal organs affected by viral infection are the
liver, kidneys, and eyes. The antibody titer mounted by the host after exposure
influences the outcome of infection. In general, a high titer clears virus from the
infected animal's tissues, a low titer results in disseminated disease, and an
intermediate titer is associated with immune-complex disease.

From the Department of Veterinary Clinical Sciences, The Ohio State University College
of Veterinary Medicine, Columbus, Ohio

VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE

VOLUME 30 • NUMBER 5 • SEPTEMBER 2000 1119

1120 WILLIS

Clinical Signs

Systemic
Infectious canine hepatitis is almost exclusively a disease of unvaccinated
dogs less than 1 year of age. 25 CAV-1 has a predilection for cells of the vascular
endothelium and the reticuloendothelial system, in addition to cells of the liver
parenchyma. 19 Typical signs of acute natural infection include fever, depression,
abdominal pain, anorexia, vomiting, diarrhea, hematemesis, petechia of mucous
membranes, and lymphadenopathy. Biochemical abnormalities are often refer-
able to hepatic dysfunction, and the coagulation profile may be suggestive of
disseminated intravascular coagulation. Chronic disease can produce hepatic
inflammation and cirrhosis, with resultant ascites, weight loss, and hepatic
encephalopathy. Mild disease may present as an inapparent pharyngitis or
tonsillitis. CAV-1 may persist asymptomatically in the renal tubular epithelium
for long periods despite the presence of circulating antibodies. 52 Although CAV-
1-related renal disease is associated with cell-mediated hypersensitivity (type
IV) in the interstitial tissues causing a tubular necrosis and interstitial nephritis,
a transient immune-complex-associated glomerulonephritis occurs in some in-
fected dogs. Unlike the potential hepatic complications, no evidence suggests
that chronic progressive renal disease results from infection with CAV-1.25

Ocular
The ocular manifestations of infectious canine hepatitis were first reported
in 1947.43 Ocular disease occurs spontaneously in approximately 20% of dogs
recovering from natural infection,16 and similar ocular manifestations have been
reported following vaccination with MLV strains of CAV-1. 16• 19 The characteristic
ocular reactions associated with CAV-1 are corneal edema and inflammation of
the anterior uveal tract. Unilateral disease is most common, although bilateral
effects may occur. Two separate phases of intraocular inflammation can be
distinguished. The first phase, which manifests clinically as a mild uveitis and
photophobia, occurs during the period of clinical or subclinical illness as a result
of viral replication in the eye, particularly in the anterior uvea. This phase is
characterized histologically by edema of the iris and mononuclear cell invasion
of the iris and trabecular meshwork. 10 The second phase of inflammation, caus-
ing keratouveitis, of which corneal edema is usually the more obvious compo-
nent, is a consequence of type ill hypersensitivity (immune-complex disease).
The release of viral antigen from infected corneal endothelial cells is followed
by the formation of immune complexes in the aqueous fluid; these complexes,
in tum, are phagocytosed by neutrophils and macrophages attracted into the
anterior chamber by complement factors and may themselves be directly cyto-
toxic to the corneal endothelium.52 Damage to the corneal endothelium allows
fluid to accumulate in the corneal stroma, resulting in corneal edema.
During the stage of mild anterior uveitis in experimentally infected dogs,
virus was isolated from the aqueous fluid, and, by electron microscopy, viral
replication was identified in corneal endothelial cells.U Later at the stage of more
severe anterior uveitis and corneal edema, virus was not isolated from the
aqueous fluid, and cells containing intranuclear (replicating) virus were not
found. ln eyes showing corneal opacification, viral antigen and antibody were
consistently demonstrated by immunofluorescence, although live virus could
not be recovered. 11 Precipitating-type antibody seems to be essential for the
reaction. Higher concentrations of antibody have been found in the aqueous
 CANINE VIRAL INFECTIONS 1121

fluids from opaque eyes of dogs that showed unilateral opacities than in the
contralateral nonopaque eye of the same animal. Phagocytized viral-antibody
complexes have been identified in areas of most prominent endothelial cell
destruction in the cornea. 1
At the onset of ocular inflammation, clinical evidence of anterior uveitis
may precede visible corneal change by up to several hours. The pupil may be
constricted, the iris may be dull and sometimes thickened, and the intraocular
pressure may be low. Aqueous flare and hypopyon (inflammatory cells settled
out ventrally in the anterior chamber) may also be evident. By the time corneal
clouding is greatest, the anterior uveitis and the associated pain or discomfort
normally subsides, although, occasionally, the uveitis persists16 (Fig. lA). The

Figure 1. A, A young mixed-breed dog with diffuse corneal edema in the left eye associated
with recovery from infectious canine hepatitis. Persistent anterior uveitis is present in the
left eye. Note the miosis in the left pupil compared with the dilated right pupil. B, Close-up
view of the left eye. The corneal opacification is diffuse, with a characteristic granular
appearance attributed to edema fluid trapped within the corneal stroma. (Courtesy of Milton
Wyman, DVM, Powell, OH.)
1122 WILLIS

corneal opacification is typically diffuse and has a characteristic mottled appear-

ance resulting primarily from separation of the stromal lamellae by edema fluid
(Fig. 1B). Occasionally, the cornea is only segmentally affected, such cases being
more transient. 16 Congestion of the episcleral vessels sometimes accompanies
the corneal edema. The thickness of the cornea, which can be best appreciated
with the slit lamp, increases variably. The presence of edema in the corneal
stroma can cause marked deformation of the corneal curvature resulting in
keratoconus 3• 16 (Fig. 2).
Corneal changes often resolve as quickly as they arise. 16 Clearance of the
edema usually begins at the limbus. Although many cases seem to resolve
completely and without complication, cellular debris may often be seen on the
corneal endothelium. Sometimes a recovered eye will develop hyperpigmenta-
tion of the iris, which can be an indication of prior uveal inflammation. A rise
in intraocular pressure is sometimes encountered within a few days of blockage
of the iridocorneal angle, 10 and clinical glaucoma may be a sequela to severe
CAV-1-related uveitis. Buphthalmia (globe enlargement) can occur rapidly in
puppies with glaucoma owing to the increased elasticity of the fibrous tunic.
After recovery from the disease, an intact endothelial cell layer has been ob-
served in some dogs, 1 however, in some of these dogs, the corneal edema fails
to resolve, presumably owing to permanent endothelial cell damage. Bullous
keratopathy with recurrent corneal ulceration can occur in such cases.
A series of cases of CAV-1-induced ocular disease suggested an increased
susceptibility of the Afghan HoundY In a litter of Afghan Hound puppies
inoculated with a commercial vaccine containing attenuated CAV-1, three pup-
pies developed corneal edema, and the litter as a whole showed marked febrile
and serologic responses to the virus. Under experimental conditions, Afghan
Hounds inoculated with CAV-1 at two levels of attenuation showed more pro-
found clinical responses when compared with Beagles receiving similar inocu-
late. An enhanced generalized susceptibility to infection was suggested as a

Figure 2. Lateral view of the left eye of a dog with marked corneal edema secondary to
natural infection with canine adenovirus type 1. The central cornea has a subtle conical
shape, characterizing early secondary keratoconus. (Courtesy of Milton Wyman, DVM,
Powell, OH.)
 CANINE VIRAL INFECTIONS 1123

possible explanation for the greater incidence of CAV-1-induced ocular lesions

in this breed. 17
The incidence of ocular lesions resulting from vaccination with MLV CAV-1
vaccines has been estimated at 0.4%. 18 The observation of a temporal relationship
between the onset of ophthalmic signs and administration of vaccine stimulated
the development of new vaccines incorporating canine adenovirus type 2 (CAV-
2), a serotype that has not been shown to cause endogenous ocular disease.'
Although CAV-2 can replicate within the eye, this replication has only been
demonstrated when virus is injected directly into the anterior chamber. 3

Diagnostics

Dramatic unilateral corneal edema presenting in a young dog is suggestive

of CAV-1-related disease. The history may suggest a period of mild transient
systemic disease preceding the onset of ophthalmic signs by 1 to 3 weeks. Blood
work may indicate hepatic enzyme stimulation; however, no specific practical
diagnostic tests are available for confirmation of infectious canine hepatitis.
Comparison of pupil position with transillumination of both eyes may reveal
anisocoria with miosis in the affected eye owing to anterior uveitis (see Fig. 1).
Glaucoma may be established at presentation, which should be confirmed with
measurement of intraocular pressure.

Prevention

Maternal antibody begins to decline in puppies by 5 to 7 weeks of age.

Inactivated vaccines do not produce lesions in dogs but must be given frequently
to provide protection equal to MLV vaccines. Lifelong immunity is afforded by
MLV CAV-1 and CAV-2 vaccines, but vaccine-associated ocular and renal disease
has been observed in dogs following CAV-1 MLV vaccines. CAV-2 vaccines do
not usually produce ocular or renal disease but may localize in the upper
respiratory tract, causing respiratory signs.

Therapy

Anterior uveitis can be treated with topical prednisolone acetate at a rate

appropriate with the degree of inflammation. Ophthalmic atropine can be given
judiciously to paralyze the iridociliary musculature for pain management and
stabilization of the blood-aqueous barrier. Concurrent glaucoma can be managed
with topical and systemic therapy; atropine therapy should be avoided. Symp-
tomatic therapy for severe corneal edema associated with bullous keratopathy or
keratoconus may include topical NaCl 5% ophthalmic ointment for its transient
osmotic effect. Eyes that are severely affected by secondary changes and that are
nonresponsive to medical therapy may best be managed with enucleation.

DISTEMPER

Canine distemper is caused by a highly contagious RNA virus in the

Paramyxoviridae family. Secondary bacterial infections and neurologic dysfunc-
1124 WILLIS

tion commonly complicate carune distemper virus (CDV) infection in dogs, and
ophthalmic manifestations may impact permanently on ocular health and vision.

Transmission

Canine distemper virus is environmentally labile and is inactivated by heat

and drying, sunlight, and most detergents. Survival times of CDV are longer at
colder temperatures. 26 The virus is shed in all body secretions, in particular from
respiratory exudates. Virus can be excreted up to 60 to 90 days postinfection,
although shorter periods of shedding are more typical. Transplacental infection
can occur. 31 Unvaccinated, weaned puppies (3-6 months old) are the most
susceptible to infection with CDV.

Pathogenesis

Canine distemper virus spreads by aerosol droplets and replicates in the

upper respiratory tract and associated lymphoid tissues. 26 Virus then localizes in
most epithelial and central nervous system tissues. Disease manifestations relate
to the immunocompetence of the host and the virulence of the viral strain. 33• 34

Clinical Signs

Systemic
Inapparent or mild disease associated with CDV infection includes list-
lessness, inappetence, and additional clinical signs including oculonasal dis-
charge, cough, and fever. Severe multisystemic disease is characterized by gastro-
intestinal signs (e.g., anorexia, vomiting and diarrhea, tenesmus, dehydration,
and, potentially, intussusception) and respiratory symptoms. The associated
cough is initially dry but rapidly becomes moist and productive. Nasal and
digital pad hyperkeratosis is usually associated with central nervous system
infection.
Neurologic signs are typically evident 1 to 3 weeks after recovery from
systemic infection with CDV. 32 Young or immunodeficient puppies have direct
viral injury to the central nervous system and develop acute encephalomyelitis. 33
Slightly older or immunocompetent pups develop nonsuppurative encephalo-
myelitis. Older immunocompetent dogs develop immune-mediated demyelinat-
ing or chronic progressive encephalomyelitis. Central nervous system complica-
tions include hyperesthesia, cervical rigidity, seizures, sensory ataxia, myoclonus,
cerebellar and vestibular signs, paraparesis, and tetraparesis.
Transplacental infection may result in abortion or birth of weak or stillborn
puppies and possible immunodeficiency in survivors. 31 Neurologic signs may
develop in transplacentally infected puppies within the first 4 to 6 weeks of life.
Enamel hypoplasia20 and cardiomyopathy29 may develop with neonatal infection.

Ocular
The effect of CDV on ophthalmic tissues is highly variable and may involve
one or multiple structures. Eyelid skin lesions were studied in a 3-year-old male
 CANINE VIRAL INFECTIONS 1125

Maltese dog with distemper. 35 Hyperkeratosis and parakeratosis with vesicles

and pustule formation were the outstanding features of the skin lesions around
the eye, nose, and mouth. Multinucleated syncytial giant cells together with
nuclear and cytoplasmic inclusion bodies containing viral particles and viral
antigen were scattered in the epidermis and epidermal appendages. These find-
ings suggested a direct viral attack on the skin.
Acute conjunctivitis may occur in the first few weeks postinfection, and a
catarrhal exudate is frequently produced. 24 Within 7 to 10 days postinfection, the
catarrhal exudate usually changes to a mucopurulent discharge (Fig. 3). Acute
and chronic keratoconjunctivitis sicca have been associated with canine distem-
per.23· 36· 44 The clinical signs associated with keratoconjunctivitis sicca are refer-
able to the duration and severity of the tear deficiency and are associated
with acute dacryoadenitis. 24 Marked blepharospasm and progressive corneal
ulceration in addition to mucopurulent discharge frequently accompany acute
keratoconjunctivitis sicca. Mucopurulent discharge, chronic conjunctival in-
flammation, and corneal vascularization and pigmentation characterize chronic
disease. Crystalline inclusions were identified in the cytoplasm of several un-
identified cell processes, as well as in myoepithelial and epithelial cells within
the gland of the nictitating membrane of a dog with systemic signs consistent
with distemper and acute keratoconjunctivitis sicca.36 These inclusions were
speculated to be CDV nucleocapsids. Distemper-associated keratoconjunctivitis
sicca was reported to resolve in one case approximately 7 weeks after the initial
presentation.36
Mild asymptomatic anterior uveitis is a component of experimentally in-
duced canine distemper, although significant primary anterior uveitis is an
uncommon manifestation of natural infection.23, 48 The histologic correlate is
mononuclear cell infiltration and giant cell formation w ithin the anterior uveal
tract, in particular in the trabecular meshwork. Intranuclear and intracytoplasmic
inclusions have been found within the anterior uvea.47 Intracytoplasmic inclu-
sions suggestive of CDV were identified in the nonpigmented ciliary epithelium
of an eye from a 7-year old Poodle with neurologic signs, bilateral conjunctivitis,
and active nongranulomatous chorioretinitis.<2
Chorioretinitis has been reported frequently in association with CDV infec-
tion,6• 23· 30· 50 and CDV inclusion bodies have been identified in retinal glial nuclei.
Most fundic lesions are seen in the peripheral and midperipheral nontapetal

Figure 3. Conjunctivitis in a dog with canine distemper. The palpebral conjunctiva is most
severely affected, and mucoid discharge is present in the inferomedial conjunctival cul-de-
sac. (Courtesy of Sheryl Krohne, DVM, West Lafayette, IN.)
1126 WILLIS

Figure 4. A fundus image from the nontapetal region of a dog with canine distemper
demonstrating multiple irregular, gray retinal lesions. Demarcated areas of choroidal depig-
mentation are also present. (Courtesy of Sheryl Krohne, DVM, West Lafayette, IN.)

fundus. 23 Acute retinitis is characterized by congestion and perivascular cuffing

of retinal blood vessels and associated retinal edema. These lesions correspond
ophthalmoscopically to a gray appearance around retinal blood vessels with
hazy, ill-defined borders (Figs. 4 and 5). Retinochoroidal scars have well-defined
margins and may have a silver-tan coloration.23 Hyperreflective foci in the

Figure 5. A fundus image from the nontapetal region of a dog with canine distemper.
Multiple gray-white foci with fuzzy borders are present beneath a retinal vessel. (Courtesy
of Sheryl Krohne, DVM, West Lafayette, IN.)
 CANINE VIRAL INFECTIONS 1127

tapetal fundus and depigmented foci in the nontapetal fundus may be present
in dogs surviving distemper and correspond histologically to focal retinal and
choroidal degeneration. 23
Optic neuritis is one of the most significant ophthalmic manifestations of
CDV infection. 30 The ophthalmoscopic appearance of optic neuritis typically
includes a raised edematous optic nerve head with an indistinct border, loss of
the central physiologic pit, and nerve head and peripapillary hemorrhages. The
immediate peripapillary region may show retinal detachment owing to retinal
edema around the disk, and inflammatory material may be seen in the vitreous
above the disk. Optic neuritis can also affect the retrobulbar optic nerve with an
absence of intraocular signs. Dogs with distemper-related optic neuritis usually
have bilateral disease, and visual disturbance or complete blindness with mydri-
asis and poor-to-absent pupillary light reflexes may be the presenting sign.
Distemper-associated blindness may also occur with inflammation of the occipi-
tal cortex or optic radiations, but pupillary reflexes are usually normal under
such circumstances. 37

Diagnostics

History and clinical signs support the diagnosis of CDV infection in an

unvaccinated neonate or stressed exposed older animals. CDV inclusions may
occasionally be identified in the conjunctival, respiratory, or urinary bladder
mucosal cells during active infection, or rarely in peripheral blood cells and bone
marrow aspirates. Immunofluorescent antibody staining of huffy coat smears,
conjunctival and respiratory epithelium, and footpad biopsy specimens may
assist in the diagnosis. 22 Positive results vary with the stage of infection but have
been reported to be as high as 54%. 50
Evaluation of cerebrospinal fluid may assist in the diagnosis of CDV in dogs
demonstrating optic neuritis. An elevated protein and cell count (predominantly
lymphocytes) is suggestive of CDV-related encephalitis. Demonstration of in-
creased anti-CDV antibody in the cerebrospinal fluid is definitive for distemper
encephalitis because antibody is locally produced, and such increases are not
present in vaccinated dogs or in dogs with systemic distemper without central
nervous system signs. 26 Cerebrospinal fluid antibody may be artifactually in-
creased owing to traumatic collection causing contamination of cerebrospinal
fluid with whole blood. To distinguish the effect of nonspecific leakage of
distemper-specific immunoglobulin G (IgG) into the cerebrospinal fluid from
serum, an antibody ratio can be determined. 26 The distemper-specific IgG in
cerebrospinal fluid is divided by that of IgG in serum. This finding is compared
with a corresponding cerebrospinal fluid-serum antibody ratio for another infec-
tious agent for which serum antibody titers are expected, such as canine adenovi-
rus (CAV). If the ratio for CDV is higher than the ratio for CAV, the de novo
production of cerebrospinal fluid antibody caused by central nervous system
infection with distemper virus is likely.

Prevention

Although immunity to canine distemper is prolonged, it is not necessarily

solid or lifelong. 26 Dogs that do not receive periodic immunizations may lose
their protection and become infected after stress, immunosuppression, or contact
with diseased individuals. Females should be vaccinated before breeding to
1128 WILLIS

increase the level of maternal antibody. Vaccination may be effective in pre-

venting systemic distemper if it is performed using MLV within 4 days of
exposure. Encephalitis has been associated with the use of MLV vaccines. 38• 49

Therapy

Supportive care is mandatory for the patient with canine distemper. Specific
therapy for the ophthalmic manifestations of CDV depends on the signs ob-.
served. Keratoconjunctivitis sicca can be treated with a combination of topical
cyclosporine and long-lasting corneal lubricating preparations. Eyes with corneal
ulcers should be treated prophylactically with broad-spectrum topical antibiotics
until reepithelialization is evident by negative fluorescein stain retention. In
dogs with progressive or apparently infected corneal ulcers, cytology and culture
and sensitivity testing should be performed. Antibiotic therapy should be dic-
tated by susceptibility test results. Optic neuritis may respond to oral corticoste-
roids.

CANINE HERPESVIRUS

Canine herpesvirus (CHV) has biologic and pathogenic properties similar

to alphaherpesviruses affecting other species, and lifelong latent infections are
typical.B CHV-associated ocular disease is uncommon or inapparent in adult
dogs, but severe ophthalmic manifestations can occur in the neonatally infected
pup.

Transmission

The susceptible newborn pup is usually infected with CHV during parturi-
tion or shortly after birth by contact with infected littermates or contaminated
fomites. Intrauterine infection can also occur. 13• 28 After oronasal exposure, CHV
is first detected in the nasal epithelium and the pharyngeal tonsils. The virus
enters the blood stream by way of macrophages, and subsequent viremia results
in viral spread throughout the body within 3 to 4 days postinfection. 13 Adult
dogs may become infected via venereal and respiratory transmission of CHV

Clinical Signs

Systemic
The postnatal infection of puppies less than 3 weeks of age with CHV
typically results in acutely fatal disease. 14 The characteristic lesions at necropsy
are disseminated foci of necrosis in the lungs, liver, and kidneys, acute hemor-
rhagic splenitis, focal suppurative meningoencephalomyelitis, and ganglioneu-
ritis. Dogs that are infected when greater than 3 to 5 weeks of age develop a
mild or inapparent upper respiratory tract infection that can be exacerbated by
concurrent infection or immunosuppression. 13 Infected puppies are depressed,
lose interest in nursing, cry persistently, and have low body temperature. Rhini-
tis, mucosal petechial hemorrhages, and buccal, vulvar, or preputial vesicles
 CANINE VIRAL INFECTIONS 1129

may be noted. Genital infections in older dogs are associated with vesicular
vaginal or preputial lesions.

Ocular
Severe ocular inflammation with subsequent retinal dysplasia and associ-
ated ocular anomalies have been observed in neonatal puppies infected with
CHV. 2 Retinal dysplasia has been reported in naturally and experimentally
infected puppies. 2' 41 Histologic findings initially include patchy depigmentation
and vacuolization of the retinal pigment epithelium and, subsequently, folding
hypertrophy and duplication as well as areas of widespread atrophy. In some
puppies, an ectopic retina has been found within cystic spaces of the optic
nerve. Histologic examination of eyes with panuveitis revealed the presence
of intranuclear inclusion bodies. Eyes with severe inflammation demonstrated
peripheral anterior synechiae, cataract, and keratitis. The presence of the virus
was confirmed by viral isolation from ocular tissues and fluorescent antibody
studies. 2
Herpesviruses were isolated from captive coyote pups with ocular discharge
and hepatomegaly. 21 The viruses were shown to be antigenically related to
CHV on the basis of specific virus neutralization with CHV antiserum. The
epizootiology of the outbreak suggested that the herpesvirus was acquired by
indirect contact with guard dogs being cared for by the same animal technicians
who cared for the coyotes. Reactivation of latent infections with asymptomatic
shedding of virus from ocular discharges occurred in dogs given repeated
immunosuppressive doses of glucocorticoids40; however, the incidence of CHV-
associated conjunctivitis in the naturally infected adult dog is unknown.

Diagnostics

Canine herpesvirus has been isolated from several organs of puppies dying
of acute systemic infection. Marked thrombocytopenia and elevation in alanine
transaminase activity can be found in infected neonatesY In recovered puppies
or older dogs, CHV replication is usually restricted to the oral mucosa, the
upper respiratory tract, and the external genitalia. Virus isolation has not been
demonstrated longer than 2 to 3 weeks postinfection. 13 Characteristic lesions in
neonatal puppies may be identified on necropsy. Polymerase chain reaction
(PCR) has been used recently to detect CHV DNA in blood and selected tissues
of infected dogs. 8 In situ hybridization and PCR are useful methods for diagnos-
ing CHV infection in formalin-fixed, paraffin-embedded tissues.45

Therapy

As noted previously, severe manifestations of CHV are usually rapidly

progressive and fatal in affected puppies, making therapy unrewarding. Under
experimental conditions, puppies with body temperatures that were increased
artificially before exposure to CHV had reduced mortality, less severe clinical
signs, and minimal pathologic changes.U Pretreatment by raising environmental
temperature is obviously not possible in natural CHV infections; however, it
could be tried for remaining unaffected puppies in a litterY
1130 WILLIS

MISCELLANEOUS INFECTIONS

Canine Viral Papillomatosis

Papillomaviruses are naturally oncogenic, producing benign warts, and are

usually species and site specific. Papillomas have been described in the conjunc-
tiva (Fig. 6), the eyelid, and the cornea. 4' 5, 7• 15, 27 Although the oral form of
papilloma has been transferred experimentally to the conjunctiva,5 1 the relation-
ship of the oral or cutaneous papillomavirus to the ocular form of the tumor
has not been established. In one recent study, papillomavirus antigen was detect-
able with immunohistochemistry techniques in 54.2% of canine ocular papillo-
mas using a polyclonal antiserum against papillomavirus antigen.46 Ocular and
adnexal papillomas may spontaneously regress9 ; however, if the masses are
locally irritating, removal is warranted. Excision or cryosurgical ablation of
adnexal papillomas is usually curative; however, the development of multiple
tumors after excision in some reported cases suggests that ocular seeding of
virus may occur during surgery.'' 15 Superficial keratectomy is recommended for
excision of corneal papillomas.

Pseudorabies

Pseudorabies is caused by an alphaherpesvirus. Although the virus is rap-

idly destroyed by ultraviolet light or drying, it can survive in the environment
for months under the proper conditions. Swine are the major hosts for pseudora-
bies and are the main source of exposure for dogs. Infection in dogs is usually
the result of ingestion of contaminated pork products. The disease in dogs is
typically peracute and fatal. The pathogenesis of pseudorabies involves local
replication of the virus, with movement along or in sensory nerves from the site
of inoculation to the brain stem. The major pathologic lesions are seen in nerves
and ganglia at the site of inoculation and in the brain stem, particularly cranial

Figure 6. A young mixed-breed dog with a wartlike papilloma on the conjunctiva near the
medial margin of the palpebral side of the nictitating membrane. This mass had spontane-
ously regressed by the time the dog was re-evaluated 1 month later.
 CANINE VIRAL INFECTIONS 1131

nerve nuclei. Severe pruritus, ptyalism, and behavioral changes are common
symptoms. 39 Reduced pupillary light responses were reported in 5% of 25 dogs
with confirmed pseudorabies. 39 Other signs referable to ophthalmic disease in
this group of dogs included mydriasis, anisocoria, blindness, ptosis, facial pare-
sis, lacrimation, and photophobia; however, no details were given with respect
to etiopathogenesis, although cranial nerve and brain stem involvement was
suspected.

SUMMARY

The ophthalmic effects of viral infection are varied. With the added possibil-
ity for pathologic effects of attenuated vaccine viruses, the diagnosis of viral
diseases can be a challenge. In many cases, ocular manifestations can provide
added support to a presumptive diagnosis of viral disease, thereby underscoring
the benefit of thorough ophthalmic examination of any animal with nonspecific
signs of illness.

References

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3. Appel M, Bistner SI, Menegus M, et a!: Pathogenicity of low-virulence strains of two
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1132 WILLIS

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A. Michelle Willis, DVM
Department of Veterinary Clinical Sciences
The Ohio State University
601 Vernon L. Tharp Street
Columbus, OH 43210