Uveitis, inflammation of the middle, highly vascular layer of tissue (uvea) in the wall of the eye, is a common, painful, and potentially vision-threatening condition in cats. The uvea comprises the iris, ciliary body, and choroid, and is situated between the sclera and inner retinal layer. When uveitis occurs, regardless of etiology, it is due to the release of inflammatory mediators following cell injury. This in turn causes disruption of the blood-aqueous barrier, allowing inflammatory cells, proteins, and even more inflammatory mediators to flood into the uveal stroma, anterior chamber, and vitreous of the eye. At this point, uveitis becomes clinically apparent.
The causes of feline uveitis are classified as either exogenous, owing to trauma, corneal ulceration, or lens luxation, or endogenous, due to infection, neoplasia, or immune-mediated conditions. Endogenous uveitis may also be idiopathic. Exogenous uveitis is less common in cats than endogenous uveitis and its cause is usually identifiable on a thorough ocular examination. The etiology of endogenous uveitis in an individual feline patient may be difficult to determine, because the clinical presentation of endogenous uveitis can look the same regardless of etiology.
In this retrospective study, the authors reviewed the medical records of 120 cats diagnosed with endogenous uveitis between 2003 and 2015 at two referral institutions in the state of North Carolina: a private referral clinic and the North Carolina State University College of Veterinary Medicine. All of the cats included in the study had complete diagnostic workups, including clinical, clincopathological, serological, diagnostic imaging, and histopathological investigations, but not all patients had the exact same testing or workup.
All patients, except for five diagnosed with neoplasia based on cytology and histopathology, were tested serologically for at least some of these agents: retroviruses (feline leukemia, FeLV; and feline immunodeficiency virus, FIV), feline coronavirus (FCoV), Toxoplasma gondii, and Bartonellaspp., and Cryptococcus neoformans and other fungal diseases. A major goal of this study was to utilize new diagnostic tests and recent greater awareness of etiologic agents to identify an etiology of endogenous uveitis in a greater percentage of cats than could be determined in older studies. Previous studies principally relied on serum and/or aqueous humor serology or histopathology, and resulted in a significant number of cases of endogenous uveitis, up to 70%, being diagnosed as idiopathic.
The cats ranged in age from 6.5 weeks to 19 years, with a mean age of 7.62 years. Most cats (89/120) were domestic shorthairs; 9/120 were domestic longhairs, 5/120 were domestic mediumhairs; the rest represented a variety of breeds. Males (75/120) significantly outnumbered females (45/120). Bilateral uveitis was identified in 43/120, while 77/120 had unilateral uveitis.
A variety of tests were used to evaluate the patients, including retroviral ELISA testing, FCoV PCR and/or FCoV IFA, serum IgG and IgM testing for T. gondiiantibodies, Bartonellatesting using culture, PCR, IFA serology, or a combination of some of these methods. Testing for fungal diseases including blastomycosis, histoplasmosis, aspergillosis, cryptococcosis, and coccidioidomycosis, was performed in nine of the cats; one was positive for Cryptococcusantigen.
In the patient population studied, seroprevalence of infectious agents tested for was as follows: FeLV 2.7%, FIV 7.3%, FCoV 34.7%, T. gondii23.7%, Bartonella spp. 43.2%; there was a combined seroprevalence of 59.2%. However, these agents were not always found to be the cause of endogenous uveitis in the patients found to be seropositive for them.
No etiologic agent was identified in 44 (36.6%) of the cats that were tested for infectious diseases. One of these cats was diagnosed with lymphoma, and five ultimately were diagnosed with feline infectious peritonitis (FIP); the remaining 38/44 were considered to have idiopathic endogenous uveitis. However, less than half of these animals (17/38) were tested in some way for all five non-fungal infectious agents.
Eleven cases with positive FCoV serology were determined to have idiopathic uveitis rather than FIP, as their clinical signs and bloodwork did not support a diagnosis of FIP. A similar distinction for those animals seropositive for T. gondiiand Bartonella spp.was not made, since interpretation of serology for these agents is difficult. Toxoplasmosis and bartonellosis cannot be diagnosed as causes of uveitis based only on serology; there are also no pathognomonic ocular lesions associated with these agents.
Histopathology is required for a definitive diagnosis of ocular toxoplasmosis. Isolation of Bartonellabacteria is the gold standard for diagnosing bartonellosis, but healthy cats in areas endemic for Bartonellacan be bacteremic. Bartonella and T. gondiiserology or PCR, especially on aqueous humor, is very useful in ruling out these diseases as a cause of uveitis, but may not be helpful in diagnosing the cause of uveitis in an individual cat. A total of 49/120 cats (40.8%), therefore, were diagnosed with idiopathic endogenous uveitis; their average age was 8.6 years.
Six of the cats (5.8%) had neoplasia; their average age was 11.1 years. Only one of these animals had primary neoplasia (diffuse iris melanoma), while the other five had metastatic neoplasia. FIP was diagnosed in 19/120 cats (15.8%); 10 of these were diagnosed based on histopathology, while the other nine were diagnosed based on a combination of diagnostic modalities and their clinical course. The average age of patients with endogenous uveitis caused by FIP was 1.82 years. The total number of cases with a definitive cause of endogenous uveitis was 37/120 (30.8%).
FeLV is not usually a cause of primary ocular disease except when it induces lymphosarcoma. None of the study cats seropositive for FeLV had lymphoma, and none of the cats with lymphoma were FeLV positive. Anterior uveitis and conjunctivitis are more commonly associated with FIV infection; many cats with FIV will develop uveitis, and the authors concluded that FIV infection probably contributed to the uveitis in those study cats seropositive for this virus. Seropositivity for FeLV or FIV in the cats evaluated in this study was significantly lower than that found in cats with uveitis in the same geographic area in previous years.
One limitation of this study is that not all patients were consistently tested with the same method for all infectious agents of concern. The etiology of endogenous uveitis in cats appears to vary significantly with age and most likely with geographic area, as well as over time. More attentive and frequent owner and veterinary care, the widespread use of feline leukemia vaccines and effective topical flea products, and a larger number of owners electing an indoor lifestyle for their cats are all hallmarks of 21stcentury cat ownership in first world nations, and probably accounts for the reduced seroprevalence of many of the infectious diseases associated with endogenous uveitis found in this study compared to previous ones.
A stronger index of suspicion for FIP as an etiology is recommended with endogenous uveitis in very young cats, while older cats, especially those over 10 years of age, may have neoplasia. In areas where there is significant fungal disease, such as the valleys of the Mississippi River and its major tributaries, the Ohio and Missouri Rivers, and the southwestern USA, clinicians should be aware of the potential for a fungal etiology in uveitis. In regions of the country with cold or dry climates inhospitable to fleas, Bartonellaexposure may be significantly less than in areas with warm, moist climates such as North Carolina. The role of the feline herpesvirus-1 (FHV-1) in cases of endogenous feline uveitis is not clear. Although this agent is often identified as a cause of superficial ocular disease in cats, studies of the involvement of FHV-1 in endogenous uveitis have had conflicting or confusing results, and it may be that FHV-1 and other, less common, ocular or systemic infectious agents, are responsible for some of the feline uveitis cases currently labeled as idiopathic. [PJS]