Leflunomide for the Treatment of Immune-Mediated Uveitis in a Dog.

A 5 yr old castrated male bichon frise presented with chronic bilateral uveitis that had previously been controlled with systemic steroid administration for 6 mo, resulting in weight gain, polyuria, and polydipsia. To control the uveitis without systemic side effects, oral cyclosporine was started after discontinuing oral steroid, but discontinued one month later because of severe vomiting. Leflunomide (2 mg/kg q 12 hr) was initiated, and the uveitis symptoms resolved after 2 mo. The dose was tapered according to the remission of clinical signs, with no relapse during the following 13 mo. Leflunomide therapy was then discontinued due to vomiting caused by severe gastroenteritis and pancreatitis, and topical prednisolone monotherapy was continued . At 8 mo after discontinuation of leflunomide, bilateral uveitis recurred, and leflunomide therapy was resumed. However, the patient lost vision due to the progression of clinical signs at 33 mo after commencing leflunomide, and evisceration of the glaucomatous right eye was performed at 43 mo. Histopathologic examination revealed lymphocyte and plasma cell infiltration and melanin-laden macrophages in the uveal tissue, and the patient was diagnosed with immune-mediated uveitis. This case indicated that oral leflunomide may be a viable treatment option for canine idiopathic immune-mediated uveitis.

The use of shotgun label-free quantitative proteomic mass spectrometry to evaluate the inflammatory response in aqueous humor from horses with uveitis compared to ophthalmologically healthy horses.

OBJECTIVE: The objective of this study was to use shotgun label-free tandem mass spectrometry (LF-MS/MS) to evaluate aqueous humor (AH) from horses with uveitis (UH) compared to ophthalmologically healthy horses (HH). ANIMALS STUDIED: Twelve horses diagnosed with uveitis based on ophthalmic examination and six ophthalmologically healthy horses (postmortem) purchased for teaching purposes. PROCEDURES: All horses received a complete ophthalmic examination and physical exam. Aqueous paracentesis was performed on all horses and AH total protein concentrations were measured with nanodrop (TPn) and refractometry (TPr). AH samples were analyzed with shotgun LF-MS/MS and proteomic data were compared between groups using Wilcoxon rank-sum test. RESULTS: A total of 147 proteins were detected, 11 proteins had higher abundance in UH, and 38 proteins had lower abundance in UH. Proteins with higher abundance included apolipoprotein E, alpha-2-macroglobulin (A2M), alpha-2-HS-glycoprotein, prothrombin, fibrinogen, complement component 4 (C4), joining chain for IgA and IgM, afamin, and amine oxidase. There were positive correlations between TPn (p = .003) and TPr (p = .0001) compared to flare scores. CONCLUSION: Differential abundance of A2M, prothrombin, fibrinogen, and C4 indicate upregulation of the complement and coagulation cascade in equine uveitis. Proinflammatory cytokines and the complement cascade have potential as therapeutic targets for equine uveitis.

Characterisation of cataracts and other ophthalmic findings in various species of captive penguins.

BACKGROUND: The identification of ophthalmic diseases that affect vision and/or cause discomfort should be a priority in captive penguins to improve their overall health and quality of life. METHODS: A routine ophthalmological examination was performed on 80 clinically normal penguins (160 eyes), and any lesions observed were recorded. RESULTS: Ocular lesions were frequent (56% of penguins), with cataracts being the most common (48.8% of penguins). Cortical cataracts (63% of eyes) and posterior subcapsular cataracts (27.4%) were the most commonly occurring. All maturation stages were found; incipient cataracts (52.1% of eyes with cataracts) were predominant, while Morgagnian cataracts (8.2%) were the least frequent. A correlation existed between lenticular changes and increasing age. Uveitis was present in 43.8% of eyes with cataracts, and ectropion uveae was the predominant clinical sign. Other ocular findings included blepharitis (3.8% of all eyes), corneal leukoma (5.6%) and posterior lens subluxation (7.5%). LIMITATIONS: The small number of birds of some species prevented the comparison of ophthalmic findings between species. CONCLUSION: This study corroborates the high prevalence of ocular lesions in captive penguins. Cataracts were frequent and age related. Most cataracts were cortical, and the predominant maturation stage was incipient. Lens-induced uveitis was a common finding. Lowered intraocular pressure was related to cataract formation.

Etiologies of nontraumatic feline uveitis in the UK: A retrospective observational study of 72 cats.

Background: Uveitis is a common ophthalmic diagnosis in cats, that can lead to discomfort and loss of vision. Identification of nonidiopathic cases facilitates treatment and could reduce morbidity associated with this condition. Aim: To evaluate etiologies of nontraumatic uveitis in the UK, to compare diagnostic features between idiopathic cases and those with an established underlying etiology, and to investigate the association of clinical signs and abnormal diagnostic findings with a confirmed etiology. Methods: Records of cats diagnosed with uveitis at a UK referral center between August 2009 and April 2018 were retrospectively reviewed, excluding traumatic (and reflex) cases. Cases were categorized based on whether an underlying etiology had been established in cases with confirmed etiology, idiopathic, and inconclusive cases. All cases had a minimum of 12-month follow-up unless an underlying etiology had been established. Population characteristics, clinical signs, diagnostic investigation features, and results were reported. Results: 72 cases of uveitis were included, of which male cats and domestic breeds were overrepresented. An underlying etiology was determined in 23.6% of cases: 9.7% had infectious diseases, 5.6% had systemic neoplasia, 4.2% had primary ocular neoplasia, and 4.2% had metabolic disease. Idiopathic uveitis comprised 37.5% of cases, and the remaining 38.9% were inconclusive, of which 35.7% died or were euthanased within the follow-up period. Among the study population, no significant age difference was found between cats with idiopathic disease or confirmed etiology. The unilateral disease was reported in 56.9% of cases and was not different across the idiopathic cases and confirmed etiology groups. The most common ophthalmic clinical sign was an aqueous flare, followed by keratic precipitates and hypotony. Iris color change (p = 0.015) and the presence of an intraocular mass (p = 0.025) were associated with an underlying etiology. Conclusion: Idiopathic uveitis was found to be the most common diagnosis in this study population. However, a similar proportion of cases had possible underlying etiologies as a high proportion manifested systemic disease within the follow-up time. An underlying etiology could be established only in a quarter of cases. Further studies are required to standardize the investigations required when assessing cats with uveitis to minimize patient morbidity.

Polyautoimmunity manifest as inflammatory myopathy, uveitis, and progressive cutaneous depigmentation in a mixed breed dog: a case report.

BACKGROUND: Polyautoimmunity is the expression of more than one autoimmune disease in a single patient. This report documents polyautoimmunity in a mixed breed dog with concurrent uveitis, cutaneous depigmentation, and inflammatory myopathy. CASE PRESENTATION: A 1-year-old male neutered mixed breed dog was presented for progressive generalized leukotrichia and leukoderma, bilateral panuveitis, and masticatory muscle atrophy. The latter progressed to myositis of lingual, pharyngeal, and masticatory muscles confirmed by biopsy. Temporalis muscle was completely replaced by adipose and fibrous tissue, and necrotic myofibers with extensive infiltration of mononuclear cells indicated active myositis of lingual muscle. Skin biopsies showed severe melanin clumping in epidermis, hair follicles, and hair shafts, and perifollicular pigmentary incontinence. Uveitis, depigmentation, and myositis affecting the masticatory, pharyngeal, and tongue muscles were diagnosed based on clinical, histological, and laboratory findings. CONCLUSIONS: To the authors' knowledge, this is the first report of concurrent uveitis, progressive cutaneous depigmentation, and inflammatory myopathy in a dog.

Diagnosis of traumatic scleral perforation in a dog using ocular ultrasound and ultrasound biomicroscopy.

A 10-year-old spayed female Maltese dog was presented for hypotony of the right eye (OD) with decreased vision. The dorsomedial region of conjunctiva was partially swollen but the globe remained intact. Slit-lamp biomicroscopy revealed intraocular haemorrhage, uveitis, and a limbal, corneoconjunctival ulcer near the swollen conjunctiva. During ocular ultrasonography (OUS), the sclera became indented and hypotony occurred, implicating a full-thickness scleral wound. Ultrasound biomicroscopy (UBM) confirmed a full-thickness scleral defect, which was surgically apposed. The intraocular pressure normalised and the uveitis subsided post-operatively. OUS and UBM were helpful in suggesting and definitively diagnosing scleral perforation, leading to accurate treatment and good prognosis.

Use of Biologics and Stem Cells in Equine Ophthalmology.

Regenerative therapy and biologics have the promise to treat equine ocular surface diseases, including corneal ulceration or immune-mediated keratitis, or intraocular diseases such as uveitis. The use of blood-derived products such as serum or platelet-rich plasma, mesenchymal stem cells, or amniotic membrane grafts may be beneficial for the treatment of ulcerative and chronic keratitis in horses. Furthermore, the use of stem cells or gene therapy has promise for the treatment of Intraocular diseases such as equine recurrent uveitis by providing efficacious, practical, and long-term therapy for these blinding diseases.

Primary pyomyositis and uveitis in a cat.

A 6-year-old neutered male Siamese cat was referred for investigation of hindlimb ataxia and blindness of 2 weeks' duration. A swollen right hind limb, with no history of trauma, and no evidence of an external wound, was observed on physical examination. Ophthalmic examination revealed bilateral absence of the menace response and changes consistent with uveitis. Blood tests identified changes consistent with inflammation including serum amyloid A elevation. Infectious disease testing was negative. Degenerate neutrophils and bacterial cocci were detected on fine needle aspiration cytology of the affected limb. Thoracic radiography and abdominal ultrasonography identified no abnormalities. Primary pyomyositis was suspected and clindamycin was prescribed following Penrose drain tube placement. In addition, eye drops containing tobramycin, atropine, and prednisolone were administered. The clinical signs and serum amyloid A level were markedly improved after 5 days of treatment. Based on the medical history and lack of other findings, the uveitis was suspected to be secondary to the pyomyositis. The clinical signs resolved completely, and no recurrence was reported within a 6-month follow-up period. To the best of our knowledge, primary pyomyositis with uveitis has not been previously reported in cats.

Effect of gentamicin on CD3+ T-lymphocyte proliferation for treatment of equine recurrent uveitis: An in vitro study.

OBJECTIVE: The objective of the study was to determine the effect of gentamicin on CD3+ T-lymphocyte proliferation and cell viability using an in vitro cell culture model as a means of investigating the mechanism of action of low-dose intravitreal gentamicin injection. ANIMALS STUDIED: Three adult horses with no evidence of ophthalmic or systemic disease. PROCEDURE: Peripheral blood lymphocytes were treated with gentamicin at concentrations 37.5 µg/mL, 112.5 µg/mL, 187 µg/mL, 375 µg/mL, or 750 µg/mL then stimulated to proliferate with concanavalin A (ConA). 4',6-diamidino-2-phenylindole (DAPI) and carboxyfluoroscein succinimidyl ester (CSFE) were used as markers of cell viability and cell proliferation, respectively. Following 5-day culture, live cell counts and CSFE fluorescent intensity data were collected via automated cell count and flow cytometry. The experimental design was duplicated using preservative-free gentamicin and a proprietary brand formulation. Statistical analysis was performed using two-way ANOVA with Tukey's multiple comparison test. RESULTS: No statistically significant comparisons in CD3+ T-lymphocyte live cell counts and geometric mean fluorescent intensity of CSFE were identified between gentamicin concentrations or formulations. CONCLUSIONS: Gentamicin had no effect on equine peripheral blood CD3+ T-lymphocyte cell viability and proliferation in concentrations ranging from "safe" to "retinotoxic" in relation to intravitreal injection volumes. Low-dose intravitreal gentamicin may not suppress the Th1- and Th17-mediated immune response.

Ophthalmic and immunopathological characterization of systemic infectious diseases in cats.

Ocular involvement in systemic diseases is frequent in cats; however, without concurrent clinical and ophthalmic examinations with gross and/or histologic analysis of the eye, these findings can be underdiagnosed. This article aims to provide gross, histologic, and immunohistochemical characteristics of ocular lesions from cats submitted to necropsy, focusing on those caused by systemic infectious agents. Cats that died due to a systemic infectious disease were selected based on necropsy diagnosis and presence of ocular lesions. Gross, histologic, and immunohistochemical findings were recorded. From April 2018 to September 2019, 849 eyes of 428 cats were evaluated. Histologic abnormalities were seen in 29% of cases, which were classified as inflammatory (41%), neoplastic (32%), degenerative (19%), and metabolic/vascular (8%). Macroscopic changes were present in one-third of eyes with histologic lesions. Of these, 40% were attributed to inflammatory or neoplastic diseases associated with infectious agents. The most important infectious agents causing ocular disease in this study were feline leukemia virus, feline infectious peritonitis virus, and Cryptococcus sp. The most common ocular abnormalities associated with infectious agents were uveitis (anterior, posterior, or panuveitis), optic neuritis, and meningitis of the optic nerve. Ocular lesions secondary to systemic infections in cats are frequent; however, these are not always diagnosed because gross lesions are less common than histologic lesions. Therefore, both gross and histologic evaluation of the eyes of cats is recommended, mainly for cases in which the clinical suspicion or necropsy diagnosis suggests that an infectious agent might be related to the cause of death.

[Ophthalmic findings caused by Encephalitozoon cuniculi (strain III) in a dog]. / Ophthalmologische Befunde durch Enzephalitozoon cuniculi (Stamm III) bei einem Hund.

A 2-year-old female mixed-breed canine patient from Namibia presented originally with chronic uveitis. A serum antibody titer and a PCR test performed on the aqueous humor were positive for encephalitozoon cuniculi. The left eye showed an immature anterior focal cortical cataract in the periphery with suspected lens capsule rupture and signs of chronic uveitis. An incipient anterior focal cortical cataract was also perceivable in the patient's right eye. Despite local treatment as well as systemic administration of carprofen, prednisolone, and fenbendazol recurrent uveitis occurred. The patient then underwent bilateral extracapsular lensextraction via phacoemulsification. A PCR test of the lens material was positive for encephalitozoon cuniculi strain III. Recurring uveitis and secondary glaucoma 10 months post-op resulted in permanent blindness of the left eye. The patient then continued to receive local anti-inflammatory treatment. The last recheck examination of both eyes, 31 month post-op, revealed no signs of uveitis. This is the first case reported of a cataract in a canine patient caused by encephalitozoon cuniculi strain III.

Equine pectinate ligament descemetization is associated with age.

PURPOSE: To evaluate the correlation between equine pectinate ligament descemetization and ocular disease. METHODS: The pathology database of the North Carolina State University Veterinary Medical Center was searched from 2010-2021 for all equine globes. Disease status was then assigned as affected by glaucoma, uveitis, or "other" based upon clinical records. The iridocorneal angles (ICA) of each globe were evaluated for the presence of pectinate ligament descemetization, the length of descemetization, as well as for the degree of angle collapse and the extent of cellular infiltrate or proteinaceous debris. One slide from each eye was evaluated by two separate, blinded investigators (HW & TS). RESULTS: A total of 66 eyes from 61 horses were identified, with a total of 124 sections of ICA of sufficient quality to review. 16 horses were affected by uveitis, 8 by glaucoma, 7 by both glaucoma and uveitis, and 30 horses by other ocular disease, most commonly ocular surface disease or neoplasia, which served as controls. Pectinate ligament descemetization was most prevalent in the control group compared to the glaucoma and uveitis groups. Pectinate ligament descemetization length was positively correlated with age, with an increase of 13.5 µm per year of age (p = .016). Infiltrate scores and angle closure scores were higher in both the glaucoma and uveitis group compared to the control group (p < .001). CONCLUSIONS: Equine pectinate ligament descemetization appears to be correlated with increased age and should not be used as a histologic marker for the presence of glaucoma.

Feline Glaucoma.

Feline glaucoma is best categorized as either secondary, congenital and anterior segment dysgenesis associated, or primary. More than 90% of all feline glaucoma develops secondary to uveitis or intraocular neoplasia. The uveitis is usually idiopathic and assumed to be immune-mediated, whereas lymphosarcoma and diffuse iridal melanoma account for many of the intraocular neoplastic-induced glaucoma in cats. Several topical and systemic therapies are useful in the control of the inflammation and elevated intraocular pressures associated with feline glaucoma. Enucleation remains the recommended therapy for blind glaucomatous feline eyes. Enucleated globes from cats with chronic glaucoma should be submitted to an appropriate laboratory for histologic confirmation of the type of glaucoma.

Effect of Volumes of Solutions on Intraocular Pressure During Intravitreal Injection of Low Dose Gentamicin in Horses With Recurrent Uveitis: A Randomized Controlled Study.

Horses with recurrent uveitis can be treated by intravitreal injection of low dose gentamicin under sedation and after local anesthetic techniques including the retrobulbar nerve block. Since it is reported that retinal degeneration can be secondary to an acute increase of intraocular pressure (IOP), the current randomized controlled study was carried out in order to investigate the changes in IOP following retrobulbar anesthesia, with two different volumes of local anesthetic (lidocaine) solution (10 and 5 mL), and intravitreal injection of 6 mg gentamicin in two different volumes of solution (0.3 and 0.15 mL). Multivariate regression showed that IOP was significantly lower in the pathologic eye at baseline (estimated effect size -6.1 mmHg; P = .0001) and after sedation (estimated effect size -9.4 mmHg; P < .0001). The IOP was significantly higher after a 10 mL block (P .0002) but this effect was very small (+0.5 mmHg). There was no significant difference in IOP after the injection of 0.15 or 0.3 mL solution of gentamicin. There was no significant combined effect of the volume of local anesthetic used for the block and the volume of the gentamicin solution. Since the expected anesthetic effects (desensitization and akinesia) were met in all cases, the smaller volume of 5 mL of lidocaine solution would be preferable for retrobulbar block for intravitreal injections, while intravitreal injections volumes of 0.15 and 0.30 mL can be used indifferently.

A review of investigated risk factors for developing equine recurrent uveitis.

Equine recurrent uveitis (ERU) is an ocular inflammatory disease that can be difficult to manage clinically. As such, it is the leading cause of bilateral blindness for horses. ERU is suspected to have a complex autoimmune etiology with both environmental and genetic risk factors contributing to onset and disease progression in some or all cases. Work in recent years has aimed at unraveling the primary triggers, such as infectious agents and inherited breed-specific risk factors, for disease onset, persistence, and progression. This review has aimed at encompassing those factors that have been associated, implicated, or substantiated as contributors to ERU, as well as identifying areas for which additional knowledge is needed to better understand risk for disease onset and progression. A greater understanding of the risk factors for ERU will enable earlier detection and better prognosis through prevention and new therapeutics.

Risk factors for a first episode of primary uveitis in the UK and proportion of cases that experience recurrence following this first episode.

BACKGROUND: Risk factors for a first episode of primary uveitis in horses have not been determined. In addition, disease progression and the proportion of horses that develop recurrence following the original episode are not known. OBJECTIVES: To determine the risk factors for the development of a first episode of primary uveitis in horses in the UK and to document the proportion of cases that experience recurrence following this first episode. STUDY DESIGN: Prospective case-control longitudinal study. METHODS: Horses with a first episode of primary uveitis between July 2014 and August 2018 were recruited to the study. For each case, two controls were selected. A questionnaire was completed for each horse and multivariable logistic regression analysis was carried out to identify associations between horse and management-level variables and the risk of uveitis. Each case was then followed longitudinally to determine the rate of recurrence of uveitis. RESULTS: Twenty-three cases and 46 controls were recruited. Being close to a pig farm (OR 27.8, CI 1.31-592.06) and a recent history of flooding of the pasture (OR 15.43, CI 2.80-84.98) was associated with increased risk of uveitis. Being in the same owner's possession for a longer amount of time had a protective effect (OR 0.79, CI 0.68-0.93). Horses recovered uneventfully following treatment and showed no evidence of recurrence in 59.1% of the cases (n = 13). In five horses (22.7%), the initial episode of uveitis could not be controlled and required surgical therapy. Recurrence was observed in four horses (18.2%). MAIN LIMITATIONS: Small sample size. Recall bias from owners for some of the data. Possibility of selection bias. CONCLUSIONS: Clinicians can use this information to identify horses with increased risk of uveitis and provide advice to the owners of these horses. The proportion of cases that experience recurrence appears low in the UK.

Survey of ocular abnormalities in draft horses.

OBJECTIVE: To determine the prevalence of ocular disease in draft horses in the United States. ANIMALS: Draft horses of various breeds and ages. PROCEDURE: Nondilated ophthalmic examination was performed using slit lamp biomicroscopy and indirect ophthalmoscopy. Intraocular pressures were measured when possible. RESULTS: One hundred sixty-five draft horses were examined. Age range: 10 days to 33 years (mean 10.8 years, median 10 years); 87 geldings (52.7%), 71 mares (43.0%), 7 stallions (4.2%); 64 Percherons (38.8%), 51 Belgians (30.9%), 29 Clydesdales (17.6%), 15 Shires (9%), and 6 other draft breed (3.6%). Intraocular pressure: mean 24.7 mmHg OD, range 13-37 mmHg; mean 25.0 mmHg OS, range 11-37 mmHg. Vision-threatening disease was present in 9 horses (5.5%): complete cataracts 1, post-traumatic optic nerve atrophy 1, uveitis and secondary glaucoma 1, retinal detachment 1, large chorioretinal scar 3, phthisis bulbi 2. Non-vision-threatening ocular disease was present in 56 horses (33.9%) involving one or more ocular structures: eyelid trauma/notch defect 14 (8.5%), SCC-type adnexal lesions 12 (7.3%), corneal scars 16 (9.7%), keratitis 6 (3.6%), corpora nigra cyst 15 (9.1%), incipient/punctate cataract 50 (30.3%), vitreous degeneration 10 (6.1%), asteroid hyalosis 1, "bullethole" chorioretinal scars 3, RPE coloboma 1. Linear keratopathy was present in 28 horses (17%) with 2/28 having concurrent vision threatening ocular disease. CONCLUSIONS: Ocular abnormalities, in particular minor cataracts, were relatively common in this population, but not typically vision-threatening. Additionally, this survey demonstrated a greater prevalence of linear keratopathy in draft horses compared with reports in other breeds; however, it does not appear to be associated with concurrent ocular disease.

Study of ocular manifestations and humoral immune response in eyes of dogs with leishmaniasis.

BACKGROUND: Ocular manifestations in dogs with leishmaniasis are frequent and complications in affected tissues can lead to blindness. Immune processes play a very important role in the pathogenesis of ocular inflammation. Therefore, the immunology of ocular manifestations in dogs with leishmaniasis remains complex and poorly understood. OBJECTIVES: Estimation and characterisation of ocular and periocular manifestations in dogs naturally infected with Leishmania infantum and investigation of the production site of specific anti-Leishmania infantum IgG. METHODS: The present investigation used 53 confirmed dogs infected with Leishmania infantum, presenting ocular and periocular lesions, and 10 control non-infected dogs. Complete macroscopic ophthalmic examination of eyelids and globes was performed. Both total and anti-Leishmania infantum IgG antibodies were studied in sera and aqueous humour (AH) of all dogs by ELISA technique. A Goldmann-Witmer coefficient (C value) was calculated. RESULTS: The main ophthalmological findings were keratoconjunctivitis (71.7%; 38/53), hyperplasia of conjunctival lymphoid follicles (54.7%; 29/53), blepharitis (50.9%; 27/53) and uveitis (20.7%; 11/53). Ocular production of anti-Leishmania infantum IgG was detected in 73.6% (39/53) of infected dogs. There was no correlation between the antibody levels in AH and sera of the same dog. The mean anti-Leishmania infantum IgG in AH was higher in uveitis, followed by lesions affecting only the adnexa (p < 0.0001). The highest mean C values were observed for uveitis, conjunctivitis and keratitis. CONCLUSIONS: Our findings suggest that production of anti-Leishmania IgG in dogs infected with Leishmania infantum with ocular manifestations begin in situ and follows by a transfer of antibodies from the bloodstream to the AH.

Risk factors for insidious uveitis in the Knabstrupper breed.

BACKGROUND: Equine recurrent uveitis (ERU) is the leading cause of blindness for horses; previous research implicated the leopard complex spotting allele (LP) as a genetic risk factor for insidious uveitis in the Appaloosa. There is limited information about risk in the Knabstrupper. OBJECTIVE: To evaluate clinical manifestations, disease frequency and potential risk factors for ERU in Knabstrupper horses. STUDY DESIGN: Cross-sectional study. METHODS: Ocular examinations were performed on 116 horses, and based on identified anomalies, horses were classified as suspect, ERU-affected or having no clinical signs. Microagglutination testing (MAT) of serum assessed exposure to Leptospira spp. Clinical signs, age, sex, base colour, coat pattern, LP and PATN1 genotypes, percent white at birth, progressive roaning and Leptospira were assessed as risk factors using multivariable exact logistic regression, accounting for clustering at the barn level. Additionally, a pedigree analysis was performed (n = 20 cases and 21 controls), and coefficients of coancestry (CC) and inbreeding were calculated. RESULTS: Prevalence of insidious uveitis in this sample of Knabstruppers was 20.7%. Similar to findings for Appaloosas, LP homozygotes had higher odds of uveitis compared with true solid (N/N) horses (LP/LP OR = 7.64, 95% CI [0.8 to +INF], p = 0.04) and age was also identified as a risk factor. After accounting for LP, the 16-20 age group had higher odds compared with the youngest group (OR = 13.36, 95% CI [1.4-213.4], p = 0.009). The distributions of average CC were significantly different between cases and controls (p = 0.01). MAIN LIMITATIONS: A relatively small sample size decreased the power for detecting additional associations. The progressive nature of insidious uveitis may have prevented identification of younger affected horses. CONCLUSIONS: Our data support genotyping for LP to assess risk of ERU in Knabstruppers. Additional studies are necessary to develop more robust risk models across LP breeds for earlier detection and improved clinical management.

Developing advanced therapeutics through the study of naturally occurring immune-mediated ocular disease in domestic animals.

This review, which is part of the "Currents in One Health" series, describes the importance of the study of immune-mediated ocular disease in the development of innovative therapeutics, such as cell and gene therapy for the eye. Recent examples of cell and gene therapy studies from the author's laboratory are reviewed to emphasize the importance of One Health initiatives in developing innovative therapies for ocular diseases. Spontaneous immune-mediated corneal disease is common in horses, cats, dogs, and humans. Autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) injected subconjunctivally resulted in the resolution of naturally occurring immune-mediated keratitis (IMMK) without adverse effects. These results support that autologous subconjunctival BM-MSC therapy may be a viable treatment alternative for IMMK. Furthermore, the use of subconjunctival MSCs may be an effective method to treat ocular surface immune-mediated diseases in humans and other species, including herpetic stromal keratitis and immunologic dry eye disease. Furthermore, the use of adeno-associated viral (AAV) vectors to deliver the immunosuppressive transgene cDNA of equine interleukin 10 (eqIL-10) or human leukocyte antigen G injected intravitreally was shown to be safe and inhibited the development of uveitis in the experimental autoimmune uveitis rat model. Efficacy and safety studies of ocular gene therapy in models will pave the way for clinical trials in animals with naturally occurring immune-mediated diseases, such as a therapeutic clinical trial for AAV-eqIL-10 in horses with equine recurrent uveitis.