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Retinal Müller glial cells (RMG) play a crucial role in retinal neuroinflammation, including autoimmune uveitis. Increasing evidence supports their function as active modulators of immune responses and potential atypical antigen-presenting cells (APCs). To further investigate this hypothesis, we conducted a differential proteome analysis of primary equine RMG from healthy controls and horses with equine recurrent uveitis (ERU), a spontaneous model of autoimmune uveitis. This analysis identified 310 proteins with differential abundance. Among these, the Major Histocompatibility Complex (MHC) class II and the enzyme Arginase 1 (ARG1) were significantly enriched in RMG from uveitis-affected horses, whereas Mannose Receptor C-type 2 (MRC2) and its interactor Thrombospondin 1 (THBS1) were more abundant in healthy RMG. The detection of MHC class II in equine RMG, consistent with previous studies, validates the robustness of our approach. Furthermore, the identification of ARG1 and MRC2, together with THBS1, provides new insights into the immunomodulatory and antigen-presenting properties of RMG. Immunohistochemical analyses confirmed the proteomic findings and revealed the spatial distribution of ARG1 and MRC2. ARG1 and MRC2 are thus markers for RMG in the neuroinflammatory or physiological milieu and highlight potential differences in the immune function of RMG, particularly in antigen presentation.

Canine uveodermatologic syndrome (UDS) resembles human Vogt-Koyanagi-Harada syndrome but typically lacks associated neurological signs. We report a 3-year-old Australian shepherd dog diagnosed with UDS following bilateral enucleation and histopathology. Twelve days postoperatively, neurological symptoms developed, including head tilt, circling, and deafness. Brain MRI and CSF analyses were consistent with meningoencephalitis of unknown etiology (MUE). Oral immunosuppressive therapy (prednisone and cyclosporine) resulted in substantial improvement. Eight months later, during gradual dose reduction, MUE relapsed, prompting an increase in dose to immunosuppressive levels. The dog's death due to an unrelated cause 4 mo later prompted postmortem evaluation. This report adds to the limited literature on MUE associated with UDS in dogs and underscores challenges in diagnosis and management. Literature review suggests this is the second reported case of Vogt-Koyanagi-Harada-like meningoencephalitis in a dog and the first reported case with a confirmed diagnosis via MRI and CSF analyses. Key clinical message: It is important to include UDS as a differential diagnosis for dogs that present with MUE with concurrent ocular and cutaneous signs. For dogs diagnosed with UDS on histology after enucleation, more aggressive immunosuppressive treatment or vigilant monitoring for neurological signs may help prevent or slow progression to neurological involvement., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Feline coronavirus (FCoV) is a virus endemic in cat populations. Specific genomic mutations give it a strong tropism for macrophages, allowing systemic infection and the development of a disease known as feline infectious peritonitis. This disease takes various clinical presentations, and can manifest as uveitis. Two mutations in the spike protein have been identified as possibly associated with FIP: mutations M1058L and S1060A. 193 clinical samples of aqueous humor were collected, all PCR-positive for feline coronavirus. Samples were taken either from cats with a clinical picture compatible with an ocular form of FIP (with uveitis and general clinical signs), or from cats with uveitis only. We sequenced the region of the S gene coding for positions 1058 and 1060 for 77 samples. The aim of the study was to determine whether viruses from cats with clinical signs compatible with FIP were more likely to harbor the M1058L and S1060A mutations. Our results confirm that these mutations are associated with severe disease, and also show that ocular samples from cats with uveitis alone are more likely to contain FECV., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Uveitis is common in horses, potentially turning chronic (persistent or recurrent) resulting in impaired vision or blindness. All mainstay therapeutics aims at controlling inflammation, but long-term or lifelong treatment is often needed with possibly severe side effects. Therefore, intravitreal injections with low-dose gentamicin (IVGI) have been used in attempt to give a long-lasting result with potentially less side effects., Objectives: To retrospectively assess outcome and long-term complications following one or two low-dose IVGI in Swedish horses with chronic uveitis., Study Design: Retrospective case series., Methods: Medical records of horses diagnosed with uveitis examined at the Equine Clinic of the University Animal Hospital of Sweden between 2016 and 2021 were reviewed. Inclusion criteria were horses with a diagnosis of chronic uveitis that were treated with 4 mg IVGI. After injection, tapering doses of anti-inflammatory medications were administered. Due to persistence or recurrence of uveitis despite IVGI, some horses received a second injection. A positive outcome was defined as controlled uveitis, despite no or minimal anti-inflammatory medication., Results: 32 eyes (29 horses) were included. Based on clinical evaluation, uveitis was classified as anterior (91%) or panuveitis (9%). 10 eyes were treated with IVGI twice. A positive outcome was observed in 13/32 eyes (41%). Inflammation in 9/32 eyes was controlled after the first, and in 4/10 eyes after the second IVGI treatment. Long-term complications included retinal degeneration in seven eyes, and mature cataracts in five eyes. Enucleations were performed in 14/32 eyes, due to lack of favourable response of IVGI, or due to complications, that is, glaucoma, corneal ulceration, and/or corneal mineralisation. One horse was euthanised due to painful bouts of inflammation in both eyes despite treatment., Main Limitations: Small sample size, retrospective design with no control group, no histopathology performed, infrequent sampling for Leptospira and no standardised treatment protocol after the IVGI., Conclusions: In this group of Swedish horses, predominantly diagnosed clinically with anterior uveitis, a positive outcome was observed in 41% of eyes following one or two low-dose IVGI. Retinal degeneration in the visual streak was observed in 22% of eyes, which is a higher proportion of this complication than previously described., (© 2024 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Equine recurrent uveitis (ERU) is a spontaneously occurring autoimmune disease and one of the leading causes of blindness in horses worldwide. Its similarities to autoimmune-mediated uveitis in humans make it a unique spontaneous animal model for this disease. Although many aspects of ERU pathogenesis have been elucidated, it remains not fully understood and requires further research. CD4 + T cells have been a particular focus of research. In a previous study, we showed metabolic alterations in CD4 + T cells from ERU cases, including an increased basal oxygen consumption rate (OCR) and elevated compensatory glycolysis. To further investigate the underlying reasons for and consequences of these metabolic changes, we quantified reactive oxygen species (ROS) production in CD4 + T cells from ERU cases and compared it to healthy controls, revealing significantly higher ROS production in ERU-affected horses. Additionally, we aimed to define mitochondrial fuel oxidation of glucose, glutamine, and long-chain fatty acids (LCFAs) and identified significant differences between CD4 + T cells from ERU cases and controls. CD4 + T cells from ERU cases showed a lower dependency on mitochondrial glucose oxidation and greater metabolic flexibility for the mitochondrial oxidation of glucose and LCFAs, indicating an enhanced ability to switch to alternative fuels when necessary.

Immune-mediated ocular inflammation is a common clinical diagnosis reached for horses with keratitis and uveitis. This diagnosis is made as a diagnosis of exclusion following a thorough effort to rule out an underlying cause for the inflammation, most importantly infectious and neoplastic disease. Practically, response to ophthalmic and systemic anti-inflammatory or immunomodulatory medications is used to support a diagnosis of immune-mediated ocular inflammation; however, such medications are often contraindicated in the face of infection or neoplasia. This article will summarize our current understanding and approach to the diagnosis and management of immune-mediated keratitis and recurrent or insidious uveitis in horses., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to describe the clinical presentation, histopathology, management, and outcome of nodular histiocytic iritis, an intraocular variant of nodular granulomatous episcleritis (NGE)., Methods: A retrospective review of the medical records of five dogs with intraocular NGE-type inflammation as diagnosed by histopathology., Results: Four Border Collies and one crossbreed dog, aged 1.5-3.4 years (mean age 2.38 years). The clinical presentation was an extensive, raised, pale iris lesion of variable location. All cases were unilateral. The physical examination was normal. Complete blood count/serum biochemistry (n = 1) and thoracic radiography (n = 1) were normal. Ocular ultrasound (n = 2) was normal apart from increased iris thickness. Enucleation (n = 4) or excisional biopsy (iridectomy, n = 1) was performed because of suspected neoplasia. Following enucleation, the remaining, contralateral eye did not develop additional lesions (9 days-3.7 years follow-up). There was no recurrence following sector iridectomy with 5 months topical 1% prednisolone acetate (3.9 years follow-up). The histopathologic findings in all five cases indicated a focal histiocytic and lymphoplasmacytic anterior uveitis (iritis), similar to that seen in cases of NGE., Conclusion: Nodular histiocytic iritis presents as unilateral iris thickening in isolation and young Collies appear to be predisposed. The histopathological findings are similar to NGE. Although the clinical presentation resembles intraocular neoplasia, an inflammatory process should be considered, which may be amenable to medical management. Definitive diagnosis may be obtained by iris sampling., (© 2023 American College of Veterinary Ophthalmologists.)

Objective: To describe the hyperproliferation of Elschnig pearl-type posterior capsule opacification and concurrent uveitis in two canine eyes after phacoemulsification, followed by spontaneous resolution of the Elschnig pearls., Animal Studied: A 10-year-old castrated male Spitz (Case 1) and a 4-year-old spayed female Bichon Frise (Case 2)., Procedure: Elschnig pearls proliferating beyond the anterior capsulotomy site were observed in the right eye 10 months after bilateral diabetic cataract surgery (Case 1) and 7 months after unilateral cataract surgery (Case 2). In both cases, hyperproliferation occurred where the anterior capsule did not overlap with the intraocular lens (IOL), and was accompanied by aqueous flare. In Case 1, the pearls extended from the anterior capsule and adhered to the iris, causing focal posterior synechia. No other possible causes of uveitis were apparent., Results: Initially, uveitis severity improved after the administration of topical and systemic anti-inflammatory drugs. However, uveitis recurred when the dosage of anti-inflammatory treatment was reduced. The Elschnig pearls underwent morphological changes throughout the follow-up period. In both cases, the pearls beyond the anterior capsulotomy resolved spontaneously after 5 months. Only a few pearls remained between the IOL and posterior capsule, and no recurrence of pearl proliferation was observed at the last follow-up., Conclusions: To the best of our knowledge, this is the first report of spontaneous Elschnig pearl regression in dogs. Lens-induced uveitis (LIU) may have been caused by anterior chamber hyperproliferative pearls. LIU associated with hyperproliferative pearls may be managed with appropriate anti-inflammatory treatment and monitoring., (© 2023 American College of Veterinary Ophthalmologists.)

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., (© 2023 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

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., (© 2024 by American Animal Hospital Association.)

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., (© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., (© 2022 EVJ Ltd.)

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., (© 2023 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare that there is no conflict of interest.

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., (© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

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.

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., (© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

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., (© 2022 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

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., (© 2022 American College of Veterinary Ophthalmologists.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

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., (© 2022 EVJ Ltd.)

Equine recurrent uveitis (ERU) is a blinding ocular disorder among horses, and the Appaloosa horse breed is disproportionally affected by a chronic form of this intraocular inflammatory disease known as insidious uveitis. Strong breed predisposition and previous investigations suggest that there is a genetic component to the pathology of insidious uveitis among Appaloosa horses; however, no estimates of the heritability of the disease have previously been determined. This study aimed to characterize the genetic underpinning of the disease by estimating the heritability for insidious uveitis among Appaloosas. After combining two genotyping array datasets from the Illumina Equine SNP70 BeadChip and the Axiom Equine 670 K Genotyping Array, heritability was estimated for 59 affected and 83 unaffected horses using both restricted maximum likelihood (REML) and phenotype correlation - genotype correlation solvers from the linkage disequilibrium adjusted kinship software. Based on previous research, age and sex were used as covariates, and the locus responsible for the characteristic Appaloosa coat pattern (LP), previously associated with ERU risk, was included as a fixed effect ('top predictor'). Using prevalence values from 0.05 to 0.42, the heritability estimate for insidious uveitis ranged from 0.95 (SE = 0.14) to 1.74 (SE = 0.25) with LP contributing 0.16-0.33 to the estimate. This study suggests that insidious uveitis is highly heritable (REML 95% CI, h 2  = 0.68-1.0) and additional loci outside of LP are contributing to the genetic risk for insidious uveitis for Appaloosas. Once identified, these other genetic factors may lead to new disease mitigation efforts in veterinary care and breeding practices., (© 2022 Stichting International Foundation for Animal Genetics.)

Equine uveitis is a common eye disease that affect horses from different breeds, ages, and genders. Uveitis has been described as inflammation of the uvea secondary immunomediated processes or eye trauma. Renal cell carcinoma (RCC) is the most common tumor that can affect the equine kidneys. The present case describe a horse that was referred to the Veterinary Teaching Hospital of the University of Extremadura with bilateral uveitis. The horse was treated for the primary complain but the horse collapse and die during hospitalization. At necropsy, a tumoral mass in kidney with extensive in other locations as liver, lung, and lymphonodes was described. Within peritoneal cavity a pedunculated mass has been observed next to severe hemoperitoneum. Histologically, primary neoplasia and its metastasis was composed by a proliferation of epithelial cells, which were organized in a tubulopapillary pattern, similarly in the ciliary body this pattern was also observed. The diagnosis of renal carcinoma with metastasis in both uveal structures was performed. Immunomarker with CD10, AE1-AE3, and vimentin evidenced the same origin of primary neoplasia. Uveal metastasis should be included as differential diagnoses in aged horses with uveitis that not response with the medical treatment., (Copyright © 2022. Published by Elsevier Inc.)

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.

In this article, which is part of the Currents in One Health series, the role of naturally occurring ocular disease in animals is reviewed with emphasis on how the understanding of these ocular diseases contributes to one health initiatives, particularly the pathogenesis and treatment of ocular diseases common to animals and humans. Animals spontaneously develop ocular diseases that closely mimic those in humans, especially dry eye disease, herpes virus infection (cats), fungal keratitis (horses), bacterial keratoconjunctivitis, uveitis, and glaucoma. Both uveitis and glaucoma are common in domestic animals and humans, and many similarities exist in pathogenesis, genetics, and response to therapy. Furthermore, the study of inherited retinal disease in animals has particularly epitomized the one health concept, specifically the collaborative efforts of multiple disciplines working to attain optimal health for people and animals. Through this study of retinal disease in dogs, innovative therapies such as gene therapy have been developed. A unique opportunity exists to study ocular disease in shared environments to better understand the interplay between the environment, genetics, and ocular disease in both animals and humans. The companion Currents in One Health by Gilger, AJVR, December 2022, addresses in more detail recent studies of noninfectious immune-mediated animal ocular disease and their role in advancing ocular health globally.

Background: Due to recent developments in artificial intelligence, deep learning, and smart-device-technology, diagnostic software may be developed which can be executed offline as an app on smartphones using their high-resolution cameras and increasing processing power to directly analyse photos taken on the device., Objectives: A software tool was developed to aid in the diagnosis of equine ophthalmic diseases, especially uveitis., Study Design: Prospective comparison of software and clinical diagnoses., Methods: A deep learning approach for image classification was used to train software by analysing photographs of equine eyes to make a statement on whether the horse was displaying signs of uveitis or other ophthalmic diseases. Four basis networks of different sizes (MobileNetV2, InceptionV3, VGG16, VGG19) with modified top-layers were evaluated. Convolutional Neural Networks (CNN) were trained on 2346 pictures of equine eyes, which were augmented to 9384 images. 261 separate unmodified images were used to evaluate the performance of the trained network., Results: Cross validation showed accuracy of 99.82% on training data and 96.66% on validation data when distinguishing between three categories (uveitis, other ophthalmic diseases, healthy)., Main Limitations: One source of selection bias for the artificial intelligence presumably was the increased pupil size, which was mainly present in horses with ophthalmic diseases due to the use of mydriatics, and was not homogeneously dispersed in all categories of the dataset., Conclusions: Our system for detection of equine uveitis is unique and novel and can differentiate between uveitis and other equine ophthalmic diseases. Its development also serves as a proof-of-concept for image-based detection of ophthalmic diseases in general and as a basis for its further use and expansion., (© 2021 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Equine recurrent uveitis (ERU) is an autoimmune disease defined by inflammation of the uveal tract of the eye. The cause of ERU is thought to be complex, involving both genetic and environmental factors. The purpose of this study was to investigate potential genetic risk factors for ERU in the Icelandic horse. Fifty-six Icelandic horses (11 affected with ERU and 45 controls) living in Denmark and the USA, eight years or older, were included in the study. A case-control GWAS was performed using the GGP Equine 80K array on the Illumina Infinium HD Beadchip using 40 horses. A mixed linear model analysis identified a single SNP on ECA 11 (BIEC2&#95;141650; NC&#95;009154.3:g.3817009A>G) that reached genome-wide significance (p = 1.79 × 10 -7 ). This variant was within an intron of tissue inhibitor of metalloproteinase 2 (TIMP2), a gene previously implicated in ERU. Sanger sequencing identified a single coding variant in this gene; however it was a synonymous mutation (NC&#95;009154.3:g.3858193C>T) and was not perfectly concordant with ERU phenotype (p = 0.68). Further investigation of TIMP2 is warranted. Additional horses and markers are needed to identify other potential loci worthy of further investigation as contributors to ERU risk in Icelandic horses., (© 2022 Stichting International Foundation for Animal Genetics.)

Equine recurrent uveitis (ERU) is a painful and debilitating autoimmune disease and represents the only spontaneous model of human recurrent uveitis (RU). Despite the efficacy of existing treatments, RU remains a leading cause of visual handicap in horses and humans. Cytokines, which utilize Janus kinase 2 (Jak2) for signaling, drive the inflammatory processes in ERU that promote blindness. Notably, suppressor of cytokine signaling 1 (SOCS1), which naturally limits the activation of Jak2 through binding interactions, is often deficient in autoimmune disease patients. Significantly, we previously showed that topical administration of a SOCS1 peptide mimic (SOCS1-KIR) mitigated induced rodent uveitis. In this pilot study, we test the potential to translate the therapeutic efficacy observed in experimental rodent uveitis to equine patient disease. Through bioinformatics and peptide binding assays we demonstrate putative binding of the SOCS1-KIR peptide to equine Jak2. We also show that topical, or intravitreal injection of SOCS1-KIR was well tolerated within the equine eye through physical and ophthalmic examinations. Finally, we show that topical SOCS1-KIR administration was associated with significant clinical ERU improvement. Together, these results provide a scientific rationale, and supporting experimental evidence for the therapeutic use of a SOCS1 mimetic peptide in RU., (© 2022. The Author(s).)

Purpose: To describe the most common ocular abnormalities in the Icelandic horse with focus on equine recurrent uveitis (ERU) and association between ocular abnormalities and summer eczema and coat colors., Methods: A descriptive cross-sectional study. A complete physical and ophthalmic examination as well as measurement of serum titers for Leptospira serovariants was performed on Icelandic horses from Denmark (DK) and the United States (USA)., Results: One hundred and twelve Icelandic horses living in DK and 26 Icelandic horses living in the United States were included in this study (total of 138 horses, 274 eyes). The three most common ocular abnormalities were follicular conjunctivitis (55.8%, 153/274 eyes), cataracts (27.4%, 75/274 eyes), and multifocal chorioretinopathy ("bullet holes"; 19%, 52/274 eyes). The prevalence for ERU among Icelandic horses aged "eight years and older" was 8% (6/75 horses). The "insidious ERU" type was found in 83% of the ERU cohort (5/6 horses), while "classic ERU" was found in 17% (1/6 horses). A correlation between ERU and cataracts was found in the population (p < .01). Leptospiral serology results were not associated with ERU in either DK or US-Icelandic horses (p = 1.00, p = 1.00, respectively). ERU was not associated with summer eczema (p = .49), and no coat colors were associated with the ocular abnormalities found in the Icelandic horse (all p-values > .05)., Conclusion: Follicular conjunctivitis, cataracts, and multifocal chorioretinopathy were the three most common ocular abnormalities findings. Icelandic horses who were 8 years or older had an 8% prevalence for ERU. Summer eczema and coat color were not associated with evidence of ERU or other ocular abnormalities., (© 2021 American College of Veterinary Ophthalmologists.)

The objective of this study was to determine the complication risk and prevalence after phacoemulsification in cats with presumed congenital/inherited cataracts. Twelve client-owned cats were included in the study. This retrospective study spanned 13 yr and involved 22 eyes. The median age at the time of surgery was 15 mo (range: 4.5-168 mo of age). Recorded complications were 3 eyes developed postoperative ocular hypertension, 1 eye developed glaucoma, 7 eyes developed feline herpes virus-1 signs, and 7 eyes developed postoperative uveitis >2 wk after surgery. No eyes had developed intraocular sarcomas at the time of their last exam. All eyes remained visual at last follow-up (range: 0.5-121 mo). Success was defined as a comfortable and visual eye without intraocular neoplasia, glaucoma, a partial or complete retinal detachment, or uveitis that occurred >2 wk after surgery or persisted longer than 2 wk. Twenty-one out of 22 eyes had a successful outcome. In this study, cats with presumed congenital/juvenile cataracts who underwent phacoemulsification had an excellent outcome., (© 2022 by American Animal Hospital Association.)

Objective: Domestic Cat Hepadnavirus (DCH) is a novel virus recently identified in the domestic cat. Currently, little is known regarding its clinical significance. The hepadnaviridae family includes the Hepatitis B Virus (HBV). Co-infection of HBV and Hepatitis C in humans increases the risk of uveitis. We aimed to determine whether DCH is present in the United Kingdom (UK) and whether DCH warrants investigation as a potential cause of uveitis in cats., Procedures: Clinical records from the Royal Veterinary College (RVC) and the Animal Health Trust (AHT) were reviewed for feline cases diagnosed with endogenous uveitis. A healthy control group was identified from cats presented to the RVC as blood donors. DNA was extracted from stored blood samples using commercially available kits. Polymerase chain reaction assays were performed to confirm the presence of feline DNA and to detect the presence of DCH DNA using previously described protocols., Results: Blood samples were available from 65 cats with endogenous uveitis and 43 healthy control cats. Two blood samples from cats with endogenous uveitis tested positive for the presence of DCH DNA. DCH DNA was not detected in the control group. There was no statistically significant difference between the prevalence of DCH between the groups., Conclusions: Domestic Cat Hepadnavirus is present in the UK. This study failed to demonstrate a conclusive link between DCH and uveitis in cats, although further studies to investigate an association with other feline diseases are warranted., (© 2021 American College of Veterinary Ophthalmologists.)

A 4-year-old male Canada lynx (Lynx canadensis) was referred to the ophthalmology service at the University of Saskatchewan with a 7-month history of cataract and chronic phacoclastic uveitis secondary to penetrating trauma from a lynx claw. Ophthalmic examination of the right eye revealed a corneal scar, marked aqueous flare, extensive fibrovascular membranes extending from the iris to the lens, anterior and posterior synechiae, immature cataract, and anterior vitritis; the fundus was not visible. Phacoemulsification surgery and intraocular lens implantation using a custom lens of D+46 and 14 mm (An-vision, West Jordan, Utah, USA) was performed. Post-operative medications included sub-conjunctival injections of atropine, cefazolin, and triamcinolone, and oral doxycycline and prednisolone. At the 5-month follow-up, the uveitis was controlled, and a normal fundus was visualized; at 21 mo, the eye remained comfortable and visual. This is the first case report to describe phacoemulsification in a wild felid as a treatment for a traumatic cataract and severe phacoclastic uveitis. Key clinical message: Despite chronic phacoclastic uveitis, phacoemulsification surgery can provide a positive outcome for mature wild felids with traumatic lens rupture, even when topical treatment cannot be administered., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Equine recurrent uveitis (ERU) is a common ocular disease of horses and described as a model for human autoimmune uveitis. This immune-mediated, inflammatory condition progressively destroys the eye, ultimately leading to blindness. Genetic and autoimmune factors, next to infections with Leptospira , are discussed as key factors in the pathogenesis. Furthermore, a release of neutrophil extracellular traps (NETs) by activated neutrophils is involved. NETs are composed of decondensed chromatin and proteins that can immobilize invading pathogens. However, if NETs accumulate, they can contribute to detrimental autoimmune processes. Thus, we aimed to investigate the impact of NETs in ERU patients. Therefore, we quantified several NET-markers (cell-free DNA, nucleosomes, citrullinated histone H3, histone-myeloperoxidase complexes, interleukin-17, equine cathelicidin 1 and DNase I activity) and NET-autoantibodies in sera and vitreous body fluids (VBF) of ERU-diseased horses and correlated the data with the disease status (signalment, ERU scores and Leptospira infection status). NET markers were detected to varying degrees in VBF of diseased horses, and partially correlated to disease severity and the presence of Leptospira spp. Cell-free DNA and nucleosomes as NET markers correlate with ERU severity in total and VBF scores, despite the presence of active DNases. Additionally, a significant correlation between fundus affection in the eye and NET autoantibodies was detectable. Therefore, we further investigated the influence of VBF samples from equine patients and isolated NETs on the blood-retina barrier in a cell culture model. VBF of diseased horses significantly induced cytotoxicity in retinal pigment epithelial cells. Moreover, partially digested NETs also resulted in cytotoxic effects. In the presence of lipopolysaccharide (LPS), the main component of the leptospiral surface, both undigested and completely digested NETs were cytotoxic. Correlations between the ERU-scores and Leptospira were also calculated. Detection of leptospiral DNA, and antibody titers of the serovar Grippotyphosa correlated with disease severity. In addition, a correlation between Leptospira and several NET markers was observed in VBF. Altogether, our findings suggest a positive correlation between NET markers with disease severity and involvement of Leptospira in the VBF of ERU-diseased horses, as well as a cytotoxic effect of NETs in eyes., Competing Interests: Author KS-M is employed by IVD Innovative Veterinary Diagnostics (IVD GmbH), Seelze, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fingerhut, Yücel, Strutzberg-Minder, von Köckritz-Blickwede, Ohnesorge and de Buhr.)

An 8-year-old female spayed domestic short-haired cat was examined for recurrent unilateral anterior uveitis of 5 month's duration. No underlying cause was found on infectious disease screening. The cat also had a 4-year history of allergic or immune-mediated skin disease that was controlled with corticosteroid injections followed by long-term oral cyclosporine therapy. Medical management with frequent topical anti-inflammatory drugs (prednisolone acetate 1% suspension, diclofenac 0.1% solution) controlled the intraocular inflammation; however, the uveitis would relapse when therapy was discontinued. Eventually, secondary glaucoma developed OD and the eye was enucleated. At the time of surgery, a complete blood count showed a mild eosinophilia. Histopathology revealed a marked panuveitis characterized by an abundant accumulation of mixed inflammatory cells, with a predominantly eosinophilic infiltrate in the anterior chamber, iris, ciliary body, and choroid. No etiologic agents were found on serial sections, and there were no cellular criteria for malignancy noted. Nine months after enucleation, the chronic dermatitis appeared to be in remission despite no further medical management. This is the first known report of a primarily eosinophilic uveitis in a cat with chronic allergic skin disease and may be considered an ocular variant of feline eosinophilic granuloma complex., (© 2021 American College of Veterinary Ophthalmologists.)

Purpose: The purpose of this study was to investigate the most common causes of endogenous feline uveitis in a UK referral population and to investigate associations based on signalment., Methods: Retrospective multicenter cross-sectional study from 2010 to 2019 including cats presented to the Animal Health Trust and the Royal Veterinary College with clinical signs consistent with uveitis. Cats were included in analyzes if they had a full physical examination including an ophthalmic examination, complete blood count, serum biochemistry, and infectious disease testing for at least two diseases unless the diagnosis was found on clinical examination (eg, neoplasia)., Results: A total of 92 cats were included in the study. The majority of cats presenting with uveitis were male (66.3%). The most common causes of endogenous uveitis were idiopathic uveitis (42/92 45.7%), feline infectious peritonitis (FIP) 15/92 16.3%), and lymphoma (10/92 10.9%). Fisher's exact test showed differences in breed across diagnosis groups (p = .002) with purebred cats being overrepresented in the lymphoma and FIP groups. Kruskal-Wallis test showed differences in median age across diagnosis groups (p < .001) with cats in the FIP group having the youngest age (median 1.4 years, interquartile range (IQR) 0.4-1.8 years) and cats in the neoplasia (primary or paraneoplastic) group having the oldest age (median 12.8 IQR 10.8-13.8). Idiopathic uveitis was unilateral in 56.1% of cases, and infectious causes were unilateral in 47.8% of cases., Conclusions: The most common cause of endogenous uveitis in a population of cats in the UK was idiopathic uveitis, followed by FIP and lymphoma., (© 2021 American College of Veterinary Ophthalmologists.)

Desialylation of cell surface glycoproteins carried out by sialidases affects various immunological processes. However, the role of neuraminidase 1 (NEU1), one of the four mammalian sialidases, in inflammation and autoimmune disease is not completely unraveled to date. In this study, we analyzed the retinal expression of NEU1 in equine recurrent uveitis (ERU), a spontaneous animal model for autoimmune uveitis. Mass spectrometry revealed significantly higher abundance of NEU1 in retinal Müller glial cells (RMG) of ERU-diseased horses compared to healthy controls. Immunohistochemistry uncovered NEU1 expression along the whole Müller cell body in healthy and uveitic states and confirmed higher abundance in inflamed retina. Müller glial cells are the principal macroglial cells of the retina and play a crucial role in uveitis pathogenesis. To determine whether higher expression levels of NEU1 in uveitic RMG correlate with the desialylation of retinal cells, we performed lectin-binding assays with sialic acid-specific lectins. Through these experiments, we could demonstrate a profound loss of both α2-3- and α2-6-linked terminal sialic acids in uveitis. Hence, we hypothesize that the higher abundance of NEU1 in uveitic RMG plays an important role in the pathogenesis of uveitis by desialylation of retinal cells. As RMG become activated in the course of uveitis and actively promote inflammation, we propose that NEU1 might represent a novel activation marker for inflammatory RMG. Our data provide novel insights in the expression and implication of NEU1 in inflammation and autoimmune disease., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ophthalmic problems account for up to 20% of emergencies in equine practice. Presenting problems may involve the periocular region, adnexa, or globe. Practitioners must have the experience to restrain horses with painful ocular conditions and the knowledge of how to perform a thorough eye examination. A range of clinical skills is required for the necessary diagnostic tests such as corneal cytology, ultrasound and tonometry, and common standing surgical procedures such as eyelid repair or instillation of a subpalpebral lavage system. Therapy, which may involve frequent administration of multiple medications, must be targeted to the specific diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A 32-year-old captive female Chilean flamingo ( Phoenicopterus chilensis ) was diagnosed with a hypermature resorbed cataract in the right eye and a mature cataract with phacolytic uveitis in the left eye. No other systemic or neurologic physical abnormalities were detected. The patient was considered blind from bilateral cataracts, and with a reduced quality of life, surgery was indicated to remove the mature cataract in the left eye. Before surgery, the phacolytic uveitis was treated in the left eye for 1 week with topical and systemic anti-inflammatory and antibiotic medication. Unilateral phacoemulsification was performed on the left eye while under general anesthesia. The individual recovered uneventfully and regained vision in the left eye. The bird was returned to its enclosure 8 days after the surgical procedure. No abnormalities were noted in behavior or reintegration. Three weeks after the phacoemulsification was performed in the left eye, the individual presented with active uveitis, without vision loss, suspected secondary to incisional infection, which was managed with topical and systemic anti-inflammatory and antibiotic medication. At day 41 the patient was discharged with no disease conditions affecting the left eye, and the flamingo's vision was considered significantly improved compared with initial presentation. Phacoemulsification was safe and effective in removing the lens, resolving phacolytic uveitis, and restoring vision in spite of the postsurgical incisional infection. Some adaptations in the surgical approach and medical management are recommended on the basis of morphology, feeding habits, and behavior of this aquatic avian species to avoid postsurgical incisional infection and uveitis.

Objective: To perform retrospective analysis of captive pteropodid bats presented to the University of Florida for ocular or adnexal disease from 2003-2020., Animals Studied: Twenty-four individuals from seven species were included., Procedures: Records were analyzed for disease process, methods of treatment, and surgical techniques and complications., Results: The most frequently reported abnormality was corneal disease (79%), followed by cataracts (54%), and uveitis (42%). Corneal disease was primarily attributed to either trauma or exposure keratitis secondary to buphthalmia. The majority of uveitis appeared to be lens-induced. Five cases (21%) of glaucoma were reported, all of which accompanied lens luxation. Of the seven enucleations performed, six had post-operative complications (85.7%), including swelling at the surgical site, seroma formation, and bacterial infection. There was no significant relationship between age and trauma, age and cataract formation, sex and trauma, or species and cataract formation., Conclusions: The most common underlying cause of ocular pathology in these cases was trauma. While the bats tolerated topical and systemic treatment well, individual temperament must be taken into account when developing treatment plans, and prevention of injury is the most effective management strategy., (© 2021 American College of Veterinary Ophthalmologists.)

Objective: Equine recurrent uveitis (ERU), a chronic, immune-mediated intraocular inflammatory disease, is a common cause of blindness in horses. The severity and recurrent nature of ERU makes it difficult to treat with current therapeutics leading to a poor visual prognosis. The suprachoroidal space (SCS), a potential space between the choroid and sclera surrounding the ocular posterior segment, offers a promising alternative site for drug application to the eye. Corticosteroid administration within this space is hypothesized to be safe and effective at controlling intraocular inflammation, especially in horses with poorly responsive ERU., Animal Studied: Horses with active, poorly responsive ERU., Procedure(s): A retrospective study was performed with 29 horses (36 total eyes) that received SCS injection of triamcinolone acetonide (TA) with ERU not well controlled with standard uveitis treatment. A standardized ocular inflammation score (OIS) was used to assess inflammation at the time of injection and at follow-ups., Results: Standardized OIS revealed a significant decrease in ocular inflammation over time after SCS TA administration (p < .004). Adverse effects after injections occurred in <20% of the horses at follow-up, but some of these effects were attributed to chronic inflammation prior to effective treatment, long-term topical corticosteroid use, or complications from hospitalization rather than the SCS injections. Most horses (86.7%) in this study remained visual greater than 3 months after SCS injection., Conclusions: Based on these results, SCS TA injections appear to be a safe and possible effective treatment modality for managing poorly responsive ERU; further clinical study is warranted., (© 2021 American College of Veterinary Ophthalmologists.)

Equine recurrent uveitis (ERU) is a spontaneous, remitting-relapsing autoimmune disease driven by the adaptive immune system. Although T cells are described as the main effector cells in pathogenesis, granulocytes have also emerged as possible disease mediators. To explore the role of these innate immune cells, we investigated the whole cell proteome of granulocytes from equine recurrent uveitis cases and healthy controls. Among the 2362 proteins identified by mass spectrometry, we found 96 proteins with significantly changed abundance between groups (p < 0.05, fold change >1.2), representing 4.1% of total granulocyte proteome. Within these differential identifications, calgranulin B, a protein associated with pathogenesis in other autoimmune diseases, showed highest abundance in equine recurrent uveitis (18 fold). For a better interpretation of the results from our hypothesis-generating approach, we added a threshold for biological significance (ratio ERU/controls >2: 36 proteins) to the proteins with increased abundance in equine recurrent uveitis and analyzed their allocation to the subsets within the Immune System superpathway. The 36 differentially abundant proteins predominantly associated to RAF/MAP kinase cascade, MHC-I-mediated antigen presentation and neutrophil degranulation, suggesting a latently activated phenotype of these innate immune cells in disease. Raw data are available via ProteomeXchange with identifier PXD013648. SIGNIFICANCE: Our study provides new insights into the protein repertoire of primary equine granulocytes and identifies protein abundance changes associated to equine recurrent uveitis (ERU), an organ specific, spontaneously occurring autoimmune disease. We show that granulocyte proteins with increased abundance in ERU strongly associate to RAF/MAP kinase signaling, MHC-I antigen presentation and neutrophil degranulation, pointing to a more activated state of these cells in ERU cases. Since cells were obtained in quiescent stage of disease, latent activation of granulocytes underlines the role of these innate immune cells in ERU. These findings are highly relevant for veterinary medicine, further establishing the importance of granulocytes in this T cell-driven autoimmune disease. Moreover, they have translational quality for autoimmune uveitis in man, due to strong similarity in disease occurrence, progression and pathogenesis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Overview: Encephalitozoon cuniculi is a common obligate intracellular microsporidian parasite of rabbits that is increasingly recognised as a pathogen of cats and other mammalian species. These guidelines aim to review the literature on feline E cuniculi infection and provide recommendations on prevention and management., Infection in Cats: E cuniculi infection should be considered as a differential diagnosis in cases of feline uveitis and cataract formation. It is not significantly associated with either chronic kidney disease or meningoencephalitis. E cuniculi infection is more common in stray or feral cats than in pet cats., Diagnosis and Treatment: Serological tests for antibody detection in the blood are easy to perform and can be useful for diagnosis, but their specificity is low as antibodies have been found in apparently healthy cats. PCR appears to be more sensitive than histopathology for diagnosis, and is more sensitive when performed on cataractous lenses compared with aqueous humour, although ease of sampling is an obvious limitation. Treatment is with fenbendazole for 3 weeks and phacoemulsification to remove microsporidia from cataractous lenses., Zoonotic Risk: E cuniculi is a potential zoonotic agent, and there is a particular risk to immunocompromised humans posed by infected rabbits. Albeit infrequent, spore shedding has been identified in cats, so care should be taken around infected cats.

Objective: In previous reports, almost half of Golden Retrievers with Pigmentary Uveitis (GRPU) have lost vision in an eye within a year of diagnosis. The purpose of this study was to determine the proportion of GRPU affected dogs with vision loss, risk factors for the development of glaucoma, and effect of treatment on disease progression., Animals Studied: Client owned Golden Retrievers., Procedures: Two complete ophthalmic examinations were performed at least 6 months apart. Visual status, presence of glaucoma, GRPU score, and treatment were recorded. A proportional odds (ordinal logistic) model was fitted to determine whether the use of topical steroidal or non-steroidal (NSAID) ophthalmic preparations was associated with a change in GRPU scores., Results: Twenty-nine Golden Retrievers, 58 eyes, were included. One eye was enucleated after the first examination. On first examination, 57/58 (98.3%) eyes and 29/29 (100%) dogs were visual. At the second examination, 48/57 (84.2%) eyes and 25/29 (86.2%) dogs were visual. Vision loss in 7/9 (77.8%) eyes was secondary to glaucoma. Posterior synechia and fibrinous material in the anterior chamber were significant risk factors for the development of glaucoma (P < .001). There was no significant difference in the change in GRPU score between eyes receiving topical steroids and topical NSAIDs (P = .14). Time between examinations was a significant factor in disease progression (increased GRPU score; P = .016)., Conclusion: The number of eyes and dogs that retained vision was higher than previous reports. No topical treatment was superior in slowing disease progression. Golden Retriever Pigmentary Uveitis is a slowly progressive disease., (© 2020 American College of Veterinary Ophthalmologists.)

Background: Uveitis is reported to be a leading cause of blindness in horses. Little work has been undertaken to date to investigate whether donkeys are affected by a similar disease prevalence., Objectives: To investigate the disease prevalence of uveitis in a population of donkeys in the UK., Study Design: Descriptive observational study., Methods: An ophthalmic examination was performed on each donkey, in a darkened stable. Each donkey underwent slit lamp biomicroscopy, and direct and/or indirect ophthalmoscopy. Fluorescein staining, STT1 and IOPs were measured when deemed clinically necessary. Pharmacological pupillary dilation was achieved using 1% tropicamide., Results: A total of 207 donkeys were examined: 139 males (67.1%) and 68 females (32.9%). Age range was 2-37 years (median: 17 years, interquartile range: 9-25 years). Three donkeys (1.5%) were blind in one eye, and one was monocular at the time of examination. Signs consistent with either previous or current uveitis were identified in eight eyes of six animals (2.9%). Clinical signs included are as follows: miosis (n = 1), corpora nigra atrophy (n = 6), anterior lens capsule pigment (n = 2), cataract (n = 8), posterior synechiae (n = 3), lens subluxation (n = 1), vitreal changes (n = 2), peripapillary scarring (n = 3) and phthisis bulbi (n = 1). Significant ocular pathology precluded fundic examination in three eyes. Three out of eight eyes (37.5%) were blinded by the pathology. The risk of uveitis was found to increase with age (OR 1.1, CI: 1.01-1.25) on univariable analysis (P = .046.)., Main Limitations: Fluorescein staining, tonometry and Schirmer tear test measurements were not performed on all donkeys., Conclusions: The disease prevalence reported here is comparable to that reported for horses in the UK. Larger prospective studies are necessary to determine whether there is a similar trend in disease prevalence in the donkey population worldwide. In addition, further investigations should aim to establish whether uveitis in donkeys is similar to the ERU syndrome seen in horses., (© 2020 EVJ Ltd.)

This is the first report of a successful treatment of a non-effusive feline infectious peritonitis (FIP) uveitis case using an oral adenosine nucleoside analogue drug and feline interferon omega, and alpha-1 acid glycoprotein (AGP) as an indicator of recovery. A 2-year-old male neutered Norwegian Forest Cat presented with uveitis, keratic precipitates, mesenteric lymphadenopathy and weight loss. The cat was hypergammaglobulinaemic and had a non-regenerative anaemia. Feline coronavirus (FCoV) RNA was detected in a mesenteric lymph node fine-needle aspirate by a reverse-transcriptase polymerase chain reaction-non-effusive FIP was diagnosed. Prednisolone acetate eye drops were administered three times daily for 2 weeks. Oral adenosine nucleoside analogue (Mutian) treatment started. Within 50 days of Mutian treatment, the cat had gained over one kilogram in weight, his globulin level reduced from 77 to 51 g/L and his haematocrit increased from 22 to 35%; his uveitis resolved and his sight improved. Serum AGP level reduced from 3100 to 400 μg/mL (within normal limits). Symmetric dimethylarginine (SDMA) was above normal at 28 μg/dL, reducing to 14 μg/dL on the cessation of treatment; whether the SDMA increase was due to FIP lesions in the kidney or Mutian is unknown. Mutian treatment stopped and low-dose oral recombinant feline interferon omega begun-the cat's recovery continued.