Feline uveitis: A review of its causes, diagnosis, and treatment - Veterinary Medicine
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Feline uveitis: A review of its causes, diagnosis, and treatment
Many disorders—both ocular and systemic—can result in inflammation of the uveal tract. By quickly narrowing the causes and initiating appropriate treatment, you might be able to save an affected cat's sight.


VETERINARY MEDICINE


Viral diseases

Four viral diseases in cats have been associated with uveitis—feline leukemia virus (FeLV) infection, feline immunodeficiency virus (FIV) infection, feline infectious peritonitis (FIP), and feline herpesvirus-1 (FHV-1) infection.

FeLV and lymphosarcoma. The retrovirus FeLV is transmitted both horizontally and vertically among cat populations.17,18 Two disease progressions are possible in cats infected with FeLV: 1) persistent viremia and progressive infection or 2) self-limiting, regressive infection.17 Numerous FeLV strains exist, some of which can lead to malignant transformation or cytopathic deletion of specific lymphocyte and hematopoietic cell populations.17


Figure 8. An iridal mass in a patient with lymphosarcoma resulting in dyscoria (altered pupil shape) in the left eye. (Photo courtesy of Dr. Kirk Ryan.)
A low incidence (< 2%) of ocular disease has been reported among cats infected with FeLV.18 Ocular lesions in cats with FeLV infection are unlikely to be the direct result of FeLV infection but rather neoplasia induced by the virus or related to secondary invasion of infectious agents caused by immunosuppression. The most common neoplastic disease secondary to FeLV infection is lymphosarcoma,17 which is a significant cause of uveitis in cats.19 Clinically, lymphosarcoma manifests as iridal thickening with associated flesh-colored lesions (Figure 8).17 These lesions are most commonly nodular but may be diffuse, with diffuse lesions appearing similar to uveitis secondary to other causes.20 Other ocular findings may include pink vascular corneal masses, hyphema, orbital disease,17 retinal degeneration, and hemorrhage.17,18

The most commonly used FeLV testing method is a peripheral blood ELISA that tests for the presence of the p27 antigen.17,18 As previously discussed, cats can develop a self-limiting regressive infection, so a positive ELISA result should be confirmed with an immunofluorescent antibody test or a second ELISA performed three to four months after the first test. A second positive test result is highly suggestive that the patient is persistently infected.17 Identifying neoplastic lymphocytes on histologic examination of mass lesions or cytologic examination of aqueous humor is diagnostic of ocular lymphosarcoma; however, such samples may be unrewarding, and detection of neoplasia in other body systems may be necessary.19

With regard to ocular lesions, a positive FeLV status should be evaluated with caution as not all cats infected with FeLV develop lymphosarcoma, and, as previously discussed, FeLV infection may result in uveitis secondary to other infectious diseases as a result of immunosuppression. Address ocular lesions with nonspecific therapy (see sidebar titled "Nonspecific therapy for uveitis"). In addition, systemic antivirals have been investigated and are thought to decrease the antigenemia in infected cats.17 These therapies, however, are associated with significant side effects, so the mainstay of systemic therapy remains good husbandry and supportive care. Patients with ocular lymphosarcoma should be treated with systemic chemotherapy agents since the disease manifestation is often associated with multicentric lymphosarcoma.17

FIV. This lentivirus causes an acquired immunodeficiency syndrome in cats.17,21,22 Many modes of transmission are thought to be possible, including in utero and postpartum through milk22 ; however, bite wounds are thought to be the predominant cause of viral inoculation.23 In patients infected with FIV, there is a progressive depletion of the CD4+ helper T lymphocyte population with a coinciding decrease in CD8+ T cells late in the disease process.24 Feline acquired immunodeficiency syndrome can occur months to years after primary infection with FIV and is associated with severe secondary infections, neoplastic diseases, and neurologic disorders.17,21 Ocular lesions seen in patients infected with FIV may include pars planitis, glaucoma, and chronic conjunctivitis,17 but anterior uveitis is the most frequent clinical finding.22 Ocular inflammation is thought to occur either directly in response to a cytopathic effect of the virus or secondary to immune stimulation by viral antigens in ocular tissue.22 Uveitis may also occur secondary to immunodeficiency and associated opportunistic infections with organisms such as Toxoplasma gondii. 17,22

Because FIV induces a persistent infection, a definitive diagnosis is most commonly achieved by detecting FIV-specific antibodies in blood through either an ELISA or rapid immunomigration-type assay.17,21 False positive results can be seen in cats that have received the FIV vaccine or in kittens < 12 weeks of age that have passively acquired anti-FIV antibodies from an infected or vaccinated mother.21 False negative results may also be observed in the acute phase of infection when the antibody response is undetectable.21 Treatment of ocular lesions should include nonspecific therapy of uveitis (see sidebar titled "Nonspecific therapy for uveitis"). Current systemic therapy is centered on good husbandry and supportive care, but antiviral chemotherapy and immune modulatory therapy are under investigation.21

FIP. FIP is caused by a highly fatal coronavirus that is shed mainly in feces and transmitted by ingesting or inhaling viral particles.25,26 Numerous feline coronaviruses exist, and it has been proposed that the FIP virus occurs secondary to spontaneous mutation of feline enteric coronavirus within an environment.26 Whether a cat develops clinical disease after viral exposure depends on the animal's immune response. Vasculitis is a hallmark of the disease and occurs secondary to the activation and circulation of monocytes.27 The clinical syndrome in cats occurs as either an effusive or noneffusive form; the noneffusive form is most commonly associated with ocular lesions.25 Such lesions may be present in either the anterior or posterior segment of the eye and may include iritis, keratic precipitates, fibrin within the anterior chamber, hyphema, chorioretinitis, and retinal perivascular cuffing.25

Diagnosing FIP is difficult since no reliable diagnostic testing methods are available at this time. Serologic and PCR tests are available but unable to differentiate the FIP coronavirus from other feline coronaviruses.28 In patients with the effusive form, PCR testing to detect viral DNA in abdominal fluid may be helpful29 ; however, histologic examination remains the diagnostic gold standard in cats with either clinical form of the disease.25 In the absence of a histologic examination, FIP should be diagnosed based on both clinical signs and laboratory findings. Common abnormal serum chemistry profile findings include severely elevated serum globulin concentrations, elevated hepatic enzyme activity, and increased BUN and creatinine concentrations.25 Common clinical findings in addition to ocular lesions include ascites, thoracic or pericardial effusion, icterus, diarrhea, and neurologic signs.25 Although ocular lesions can be addressed with nonspecific therapy (see sidebar titled "Nonspecific therapy for uveitis"), systemic treatment is rarely successful but may include immunosuppressive and anti-inflammatory agents and feline interferon-omega.25

FHV-1. This DNA alpha-herpesvirus is widespread among the general cat population.30,31 The virus is shed in ocular, nasal, and oral secretions and transmitted mostly by direct contact, although indirect transmission can occur.30 After infection, about 80%31 of cats become latently infected carriers. Of these, about 45% of cats can have virus reactivation, resulting in clinical disease or asymptomatic episodes of viral shedding spontaneously or after periods of stress.30,31

The most common clinical ocular manifestations of FHV-1 are conjunctivitis and keratitis, but anterior uveitis has also been a suggested manifestation of the disease.32 One study demonstrated FHV-1 DNA in the aqueous humor of 12 of 86 cats with clinical signs of anterior uveitis that had negative test results for other known causes of feline uveitis.32 This study proposed that FHV-1 gained entry into the eye through axonal transport of virus, but this hypothesis has not been investigated.32 As previously discussed, FHV-1 may reactivate in times of stress, so it remains unclear whether the intraocular FHV-1 infection is a cause or result of feline uveitis.31 Additionally, FHV-1 can replicate in conjunctival and corneal tissue and could serve as a contaminant during anterior chamber paracentesis.

Acute ocular FHV-1 infection can typically be diagnosed with virus isolation from conjunctival cytology samples.31 Other diagnostic tests available include serology and serum neutralizing antibody titers, fluorescent antibody testing on corneal or conjunctival smears, and PCR tests.30,31,33 Serologic tests are of limited value since most cats have been exposed to or vaccinated against FHV-1.32

In addition to nonspecific therapy (see sidebar titled "Nonspecific therapy for uveitis"), topical antiviral medications, including trifluridine and idoxuridine solutions, are efficacious against FHV-1 conjunctivitis and keratitis when administered as one drop in the affected eye four to six times a day for two to three weeks.34,35 As most antiviral agents are virostatic, frequent application is needed. Combined with local irritation, these factors often result in poor owner compliance.

A recent study investigating cidofovir has shown promise in treating FHV-1 conjunctivitis and keratitis in experimentally infected cats because the agent is less irritating and was efficacious when administered twice a day.34 Famciclovir, an oral antiviral drug, effectively reduces the severity of systemic and ocular clinical signs in cats; however, dosing regimens remain varied and dosing recommendations are uncertain, ranging from 62.5 mg/cat once to twice a day to 125 mg/cat three times a day.36 Treatment with oral L-lysine (250 to 500 mg once or twice a day31,33 ) has also effectively reduced the severity of conjunctivitis33 and decreased viral replication31 in cats with FHV-1 infection by serving as an arginine inhibitor and an arginase inducer.31


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