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Background: Inherited primary open-angle glaucoma (POAG) in Beagle dogs is a well-established large animal model of glaucoma and is caused by a G661R missense mutation in the ADAMTS10 gene. Using this model, the study describes early clinical disease markers for canine glaucoma. Methods: Spectral-domain optical coherence tomography (SD-OCT) was used to assess nine adult, ADAMTS10-mutant (median age 45.6 months, range 28.8–52.8 months; mean diurnal intraocular pressure (IOP): 29.9 +/− SEM 0.44 mmHg) and three related age-matched control Beagles (mean diurnal IOP: 18.0 +/− SEM 0.53 mmHg). Results: Of all the optic nerve head (ONH) parameters evaluated, the loss of myelin peak height in the horizontal plane was most significant (from 154 +/− SEM 38.4 μm to 9.3 +/− SEM 22.1 μm; p < 0.01). There was a strong significant negative correlation between myelin peak height and IOP (Spearman correlation: −0.78; p < 0.003). There were no significant differences in the thickness of any retinal layers evaluated. Conclusions: SD-OCT is a useful tool to detect early glaucomatous damage to the ONH in dogs before vision loss. Loss in myelin peak height without inner retinal thinning was identified as an early clinical disease marker. This suggests that initial degenerative changes are mostly due to the loss of myelin. [ABSTRACT FROM AUTHOR]

Objective s : To identify canine breeds at risk for ocular melanosis and to compare the clinical and histologic features between affected Cairn Terriers (CTs) and non‐Cairn Terriers (NCTs). Design: Relative risk (RR) analysis and retrospective cohort study of dogs histologically diagnosed with ocular melanosis. Procedures: The COPLOW archive was searched for globe submissions diagnosed with ocular melanosis. Six hundred fifty globes were included, and RR analysis was performed to identify at‐risk NCT breeds. A cohort of 360 CT and NCT globes diagnosed from 2013 to 2023 were included in the retrospective cohort study. Clinical data were collected from submission forms, medical records, and follow‐up surveys. One hundred fifty‐seven submissions underwent masked histologic review. Immunohistochemical staining for CD204 was performed to determine the predominance of melanophages in affected uvea from five NCTs. Results: At‐risk NCT breeds included the Boxer, Labrador Retriever, and French Bulldog. Glaucoma was the reported reason for enucleation in 79.4% of submissions. At enucleation, clinical features less prevalent in NCTs than CTs included pigmentary abnormalities in the contralateral eye (33.7% vs. 63.1%, p =.0008) and abnormal episcleral/scleral pigmentation in the enucleated globe (25.4% vs. 53.6%, p =.0008). Histologic involvement of the episclera was also less frequent in NCTs than in CTs (39.7% vs. 76.9%, p =.008). Concurrent melanocytic neoplasms arising in melanosis were more common in NCTs (24.4%) than CTs (3.9%). Melanophages were not predominant in any samples evaluated immunohistochemically. Conclusions: Several popular NCT breeds carry risk for ocular melanosis, and some clinicopathologic disease features may differ from those described in CTs. [ABSTRACT FROM AUTHOR]

Captive fish populations, such as those encompassing aquarium and pet fish, offer significant economic value and are integral to conservation, research, and education. However, these ornamental fish exhibit a reduced ability to protect their ocular surfaces, and our understanding of the ocular diseases that affect them remains limited. Although corneal neoplasms in carp are uncommon, identifying their distinct characteristics is crucial in selecting appropriate therapeutic interventions that aim to preserve vision, prevent the ocular loss, and ultimately ensure the survival of the affected fish. This study provides clinical and histopathological details of various proliferative corneal masses in Cyprininae species, including five koi (Cyprinus carpio) and four goldfish (Carassius auratus). It discusses a spectrum of neoplasms, including soft tissue sarcoma, spindle cell sarcoma, chromatophoroma, and papilloma, in addition to conditions like exuberant granulation tissue and proliferative carp pox. These findings bear significant implications for clinical decision‐making and treatment, offering valuable insights into the incidence and characteristics of corneal tumors in captive fish, which could inform further studies in this area. [ABSTRACT FROM AUTHOR]

Purpose: Angle closure glaucoma (PACG) is highly prevalent in dogs and is often refractory to medical therapy. We hypothesized that pathology affecting the post‐trabecular conventional aqueous outflow pathway contributes to persistent intraocular pressure (IOP) elevation in dogs with PACG. The goal of this study was to determine the potential for aqueous angiography (AA) and optical coherence tomography (OCT) to identify abnormalities in post‐trabecular aqueous outflow pathways in canine PACG. Methods: AA and anterior segment OCT (Spectralis HRA + OCT) were performed ex vivo in 19 enucleated canine eyes (10 normal eyes and 9 irreversibly blind eyes from canine patients enucleated for management of refractory PACG). Eyes were cannulated and maintained at physiologic IOP (10–20 mmHg) prior to intracameral infusion of fluorescent tracer. OCT scleral line scans were acquired in regions of high and low perilimbal AA signal. Eyes were then perfusion fixed and cryosections prepared from 10/10 normal and 7/9 PACG eyes and immunolabeled for a vascular endothelial marker. Results: Normal canine eyes showed segmental, circumferential limbal AA signal, whereas PACG eyes showed minimal or no AA signal. AA signal correlated with scleral lumens on OCT in normal dogs, but lumens were generally absent or flattened in PACG eyes. Collapsed vascular profiles were identified in tissue sections from PACG eyes, including those in which no lumens were identified on AA and OCT. Conclusions: In canine eyes with PACG, distal aqueous outflow channels are not identifiable by AA, despite normalization of their IOP, and intra‐scleral vascular profiles are collapsed on OCT and histopathology. [ABSTRACT FROM AUTHOR]

Objective: Investigate histopathology and spectral‐domain optical coherence tomography (OCT) imaging of wild owls with chorioretinitis and identify any potential correlation with an infectious etiology. Materials and Methods: Ophthalmic examination and retinal OCT imaging were performed on fifteen great horned (Strix varia) and barred (Bubo virginianus) owls (30 eyes) with chorioretinitis and five owls with normal eyes (10 eyes). Testing to investigate the presence of potential infectious diseases included a complete blood count, biochemistry, protein electrophoresis, West Nile virus (WNV) plaque reduction neutralization test, Toxoplasma gondii modified direct agglutination test, WNV RT‐PCR, and Avian Influenza RT‐PCR. A necropsy was performed on all owls, including ocular histopathology. Results: Fundus lesions included retinal detachment (7/15 owls), depigmented lesions (12/15), pigment clumping (8/15), and retinal tear (4/15). All birds were negative for WNV and Avian Influenza on RT‐PCR. Of the owls with chorioretinitis, 3/15 were seropositive for WNV and 7/15 for T. gondii. Optical coherence tomography of 25/30 affected eyes revealed outer retinal lesions (19/25 eyes), retinal detachment (16/25), and retinal tears (3/25). Histopathological examination revealed outer nuclear layer atrophy (19/30 eyes), retinal detachment (18/30), retinal tears (7/30), suprachoroidal hemorrhage (12/30), scleral rupture (3/30), and ossicle fracture (3/30). Conclusions: Although 20% of birds were seropositive for WNV and 46.6% for T. gondii, histopathologic findings supported that the posterior segment lesions in the study group were likely due to blunt ocular trauma rather than an infectious etiology. The results of OCT imaging and histopathology documented retinal changes most consistent with blunt ocular trauma. [ABSTRACT FROM AUTHOR]

We describe a case of chronic ocular trauma that resulted in fixed and free‐floating, pigmented epithelial iridociliary cysts, inflammation, and secondary glaucoma in a caiman (Caiman latirostris). A 20‐ to 25‐year‐old male caiman was presented with phthisis bulbi in the right eye, and congested episcleral vessels, corneal leukoma, disorganized anterior chamber, multifocal anterior synechia, and elevated intraocular pressure in the left eye. Ocular ultrasound of the left eye revealed round structures dispersed in the anterior and posterior chambers and vitreous cavity. Bilateral enucleation was performed, and gross pathology of the left eye revealed multiple pigmented cysts attached to the iris and posterior corneal surface causing marked distortion of the anterior uvea, and free‐floating in the vitreous cavity. Histopathology demonstrated heavily pigmented cystic structures of iridociliary epithelium origin carpeting the anterior segment surfaces and causing obstruction of the iridocorneal angles, leading to secondary glaucoma. To the authors' knowledge, this is the first report of iridociliary cysts in wildlife species. [ABSTRACT FROM AUTHOR]

The objectives of this retrospective study were to evaluate the histopathologic changes associated with porcupine ocular quill injuries in dogs, to discuss the various methods of quill detection when quills are not grossly visible, and to discuss the pathogenesis of delayed ocular quill injuries in dogs. Seventeen globes sustaining ocular quilling injuries from 17 dogs (1986‐2018) were identified in the COPLOW archives and the gross and histologic changes tabulated and compared. All cases were dogs, with one whole globe submitted from each patient. Sixteen of 17 cases had known or suspected porcupine encounters in the weeks or years preceding enucleation. Histopathologic findings included retinal detachment, hyphema, cataract, granulomatous to pyogranulomatous inflammation (uveitis, endophthalmitis, panophthalmitis), lens capsule rupture, suppurative phakitis, scleral perforation, stromal keratitis, breaks in Descemet's membrane, preiridal fibrovascular membrane, anterior and posterior synechia, Schnabel's cavernous atrophy, and periorbital fibrosis. Quill‐associated ocular trauma can have a significant deleterious effect on vision and result in enucleation. The time from initial quilling to the manifestation of ocular signs may be prolonged (weeks to years). Any dog presenting for ocular signs with a history of a previous porcupine encounter should be carefully checked for quill migration into the globe as the source of ocular disease. Quills may not be visible grossly, and ancillary imaging techniques can be utilized with various rates of success. [ABSTRACT FROM AUTHOR]

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design. [ABSTRACT FROM AUTHOR]

Purpose: To describe ocular clinical findings, gross/histopathologic findings, and treatment regimens in a series of migratory chuck-will's-widows (Antrostomus carolinensis) (CWW) with corneal epithelial defects. Methods: Seven CWW were presented to the South Florida Wildlife Center (SFWC). Four presented with bilateral (OU) corneal ulceration; two developed corneal ulceration OU; one had no ocular lesions. Treatment protocols for patients with corneal ulcers included the following: medical therapy only or medical therapy combined with an additional procedure. Four patients including the bird with no ocular lesions were euthanized, and one patient died. Their globes were submitted for histopathology. Two patients were released. Results: Clinical findings prior to enucleation included superficial corneal ulceration with redundant epithelium persisting weeks to >1 month. On histopathology, epithelium in nonulcerated globes was remarkably thin; this was considered normal. Common histopathologic findings of ulcerated globes revealed epithelial and conjunctival attenuation with an acellular superficial stromal layer and hypercellular mid-stromal layer. One globe healed with medical therapy and cotton tip applicator debridement. Four globes healed by combination of medical therapy, equine amnion, nictitating membrane (NM) flap, and temporary tarsorrhaphy. No globes healed with diamond burr debridement or grid keratotomy. Conclusions: Factors that may be contributing to these corneal epithelial defects include, but are not limited to, normally thin epithelium, exposure keratopathy, neurotrophic disease, epithelial turnover and inadequate stem cell recruitment, inherited/genetic causes, and unidentified infectious agents (eg, viral etiologies). Of the 12 eyes treated, one healed with medical therapy/cotton tip applicator debridement, and four healed with medical therapy/equine amnion/nictitating membrane flap/temporary tarsorrhaphy. [ABSTRACT FROM AUTHOR]

Objective: To describe the historical, clinical, and diagnostic features of small animal patients affected by cactus‐induced keratoconjunctivitis and their response to therapy. Animals studied: Three dogs and one cat. Procedures: Ophthalmic examination directed subsequent selected diagnostic tests in each case including light microscopy of extracted foreign bodies, in vivo confocal microscopy (IVCM), corneal histopathology, and corneal bacterial culture. Treatments consisted of foreign body surgical extraction with concurrent medical therapy (three cases), or medical therapy alone (one case). Results: Clinical histories obtained supported acute cactus injury in all cases. Ophthalmic abnormalities were unilateral in each case and included ulcerative keratoconjunctivitis associated with linear, microscopic conjunctival and/or corneal penetrating cactus spines, known as glochids. Light microscopy and IVCM showed glochids to be heavily barbed, consistent with the spine morphology Prickly Pear (Opuntia) cactus species. Bacterial culture yielded Proprionicimonas sp. in one case with keratomalacia. Surgical extraction of spines was challenging, and residual conjunctival and/or corneal glochids were present in all cases. Patient discomfort resolved at a median of 21 days (range 10‐51 days). Vision‐threatening complications were not observed in any case at the time of last follow‐up examination. Epithelial downgrowth, demonstrated by IVCM and histopathology, was present in one case at 108‐day follow‐up. Conclusions: Cactus‐induced keratoconjunctivitis should be considered as a differential in regions in which Opuntia cacti are prevalent, and microscopic ocular foreign bodies are observed. Although glochids are difficult to extract, positive clinical outcomes can occur in small animal patients despite the presence of residual organic corneal foreign material. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical, histopathological, and immunohistochemical features of 17 cases of ocular surface xanthogranuloma (OSX) in dogs. Methods: Archived records from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were searched for cases of canine OSX. Cases were evaluated for lipid‐laden macrophages and Touton giant cells. Seventeen cases matching those criteria were identified (1993‐2018). Clinical and epidemiological data were collected from the submission forms and additional follow‐up survey. Results: Ocular surface xanthogranuloma in dogs presented as small bland nodules. OSX commonly occurred at the limbus (8/17) or cornea (4/17). Three of 17 affected animals were less than 1‐year‐old and the average age was 6.9 years (range 0.7‐14 years). Fourteen of 17 cases did not report any lipid or metabolic abnormalities. Histologically, lesions were composed mainly of dense sheets of vacuolated lipid‐laden macrophages and Touton giant cells with scant additional inflammatory cells and an intact overlying epithelium. No recurrence was noted in cases where complete surgical resection was achieved, and medical treatment either pre or post‐resection led to only partial resolution. Conclusions: Xanthogranulomas are histiocytic lesions characterized by abundant lipid‐laden macrophages. The authors use the term, ocular surface xanthogranuloma, to describe nodules with rigidly defined cellular characteristics. Although these lesions share characteristics with human limbal xanthogranulomas, further investigation is needed to suggest the different subsets that have been reported in the medical literature. Complete surgical excision is the most effective treatment for OSX in dogs, and intralesional triamcinolone and topical steroids can be useful adjunctive therapies to surgery. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to describe and classify cats with intraocular lymphoma, determine the proportion of cases with presumed solitary ocular lymphoma (PSOL) compared with ocular manifestations of multicentric disease and assess the clinical outcomes of these patients. One hundred seventy‐two cases identified through biopsy submissions were reviewed histologically; 163 of these cases were subtyped according to the WHO classification system. Cases were categorized as having PSOL or ocular lymphoma with suspected systemic involvement (SSI) based on submission forms and follow‐up data. The majority of cases exhibited concurrent uveitis (75%) and secondary glaucoma (58%). Diffuse large B‐cell lymphoma was the most common subtype (n = 86; 53%), followed by peripheral T‐cell lymphoma (n = 44; 27%). Other subtypes included anaplastic large T‐ (n = 8; 5%) and B‐cell (n = 4; 2.5%) lymphomas, and 15 cases (9%) were negative for all immunohistochemical markers. In sixty‐nine cases (40%), adequate clinical data and sufficient survival data were obtained to distinguish PSOL from SSI. PSOL comprised the majority of cases (64%), while 36% had SSI. When covarying for age at diagnosis, the median survival time was significantly higher (P = 0.003) for cases of PSOL (154 days) versus those with SSI (69 days); hazards ratio of 0.47 for PSOL (95% CI: 0.241‐0.937). The subtype of lymphoma did not affect survival time. Cats with PSOL represent a greater proportion of the disease population, and this subset of cats with intraocular lymphoma has a better clinical outcome. [ABSTRACT FROM AUTHOR]

Purpose: To describe the clinical and histopathologic features secondary to ocular and periocular snakebites in dogs requiring enucleation. Methods: Retrospective review of patients with recorded snakebite envenomation from the archives of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) and Texas A&M Veterinary Medical Teaching Hospital (1997‐2017). The cases included in this study required witnessed snakebites to the dog by the owner, clinical signs supportive of periocular or ocular envenomation, and/or histopathologic lesions compatible with snakebites. Two groups were established: ocular bites (OB) and periocular bites (PB). Results: Nineteen cases were included in the study (OB = 16/19; PB = 3/19). Dogs affected were typically older (median 8 years; range 1‐18), and both sexes were equally represented. Left eyes (14/19) were more likely to sustain snake‐induced trauma compared to right eyes (5/19). Fifteen breeds were identified, with terriers (9/19) commonly represented. Snakes bites occurred in six US states, with the majority of cases from Texas (7/19), California (5/19), and Arizona (4/19). Common clinical signs included facial edema, corneal ulceration, keratomalacia, uveitis, hyphema, and secondary glaucoma. All eyes demonstrated vision loss prior to enucleation. Histologically, the ocular and periocular tissues contained extensive necrosis associated with envenomation. Retinal detachment, lens capsule rupture, and intraocular hemorrhage/inflammation were commonly found. Conclusions: Snakebite envenomation is a largely necrotizing disease process that can result in profound infiltrative and destructive ocular changes presumed to be related to the proteolytic factors and necrotoxins in venom. Ocular alterations secondary to snakebites may be irreversible regardless of supportive therapy instituted. [ABSTRACT FROM AUTHOR]

We describe a case series of photoreceptor dysplasia with secondary retinal degeneration in juvenile Peregrine Falcons. Six Peregrine Falcons (Falco peregrinus) and three Peregrine Falcon × Prairie Falcon (Falco mexicanus) hybrids had early-life visual deficits. Eight birds had visual defects shortly after hatching, and one bird had visual deficits first noticed at 5 mo of age. Complete ophthalmic examinations were performed in each animal. Eight of the animals had electroretinograms, and nine of the animals had their eyes examined histologically after euthanasia. Ophthalmic examinations did not reveal consistent and potentially blinding abnormalities, including an absence of ophthalmoscopic retinal lesions. Electroretinographic findings included subnormal amplitudes (with rod responses more abnormal than cone responses), with a negative b-wave amplitude occurring in one bird. Histologically, a reduction in the number of photoreceptors was present with numerous degenerative changes to the remaining photoreceptors, including frequent blunting and disorganization of photoreceptor outer segments, decreased numbers of cells in the inner nuclear layer, decreased numbers of ganglion cells, decreased thickness of the nerve fiber layer, and decreased myelinated axons within the optic nerve. Ultrastructurally, only minor cone outer segment changes and occasional phagocytic cells were seen. Results strongly suggested a primary retinopathy, characterized by photoreceptor dysplasia and secondary retinal degeneration with loss of cellular elements throughout the retina. The presence of a similar spectrum of findings in related individuals, the early age of onset, and the relative lack of other environmental, ocular, or systemic abnormalities suggested possible heritability. [ABSTRACT FROM AUTHOR]

Observational studies are a basis for much of our knowledge of veterinary pathology, yet considerations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offered advice on planning and carrying out an observational study. Part 2 of the series focuses on methodology. Our general recommendations are to consider using already-validated methods, published guidelines, data from primary sources, and quantitative analyses. We discuss 3 common methods in pathology research—histopathologic scoring, immunohistochemistry, and polymerase chain reaction—to illustrate principles of method validation. Some aspects of quality control include use of clear objective grading criteria, validation of key reagents, assessing sample quality, determining specificity and sensitivity, use of technical and biologic negative and positive controls, blinding of investigators, approaches to minimizing operator-dependent variation, measuring technical variation, and consistency in analysis of the different study groups. We close by discussing approaches to increasing the rigor of observational studies by corroborating results with complementary methods, using sufficiently large numbers of study subjects, consideration of the data in light of similar published studies, replicating the results in a second study population, and critical analysis of the study findings. [ABSTRACT FROM AUTHOR]

Spontaneously occurring ocular neoplasia is rarely reported in rabbits. This case series presents four cases of rabbits diagnosed with iridociliary tumors, which have not been previously reported in this species. Major pathological findings include epithelial tumors affecting the anterior uvea with variable pigmentation and basement membrane formation. Follow‐up information was only available for two cases, but neither showed evidence of metastasis, suggesting that the prognosis for these tumors in rabbits, as in other species, may be very good. [ABSTRACT FROM AUTHOR]

Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To describe the clinical presentations of patients diagnosed with ocular adnexal or orbital squamous cell carcinoma (SCC), which possess features similar to feline restrictive orbital myofibroblastic sarcoma (FROMS). Procedures: A retrospective review of adnexal and/or orbital SCC was performed. Cases were collected from the University of Georgia College of Veterinary Medicine and the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) (1990‐2016). Data included signalment, ophthalmic clinical signs, nonophthalmic history and clinical signs, clinician suspicion of FROMS, advanced imaging results, and subsequent histopathologic diagnosis. FROMS cases from the COPLOW over the same time span were reviewed and compared statistically to the SCC cases with a significance threshold of 0.05. Results: Nineteen cases (20 eyes) were identified with adnexal SCC with features similar to FROMS, including keratitis and eyelid/third eyelid restriction and/or thickening. There were no statistically significant differences between clinical findings in the SCC cases and the identified and compared FROMS cases (57 cases; 67 eyes), except for exophthalmos and/or resistance to retropulsion, which was less common in SCC cases (20%) than in FROMS cases (47.8%) (P = 0.027); and clinical or imaged presence of an overt eyelid or orbital mass, which was more common in the SCC cases (30%) than in the FROMS cases (4.5%) (P = 0.0010). Conclusions: SCC with adnexal involvement has many features similar to FROMS. In addition to FROMS, SCC should be considered a differential diagnosis in cats with restrictive adnexal or orbital signs and corneal changes. [ABSTRACT FROM AUTHOR]

An eleven-year-old, female spayed Boxer dog was diagnosed with a uveal schwannoma (formerly known as the spindle cell tumor of the blue-eyed dog or SCTBED) despite having a uniformly brown iris. The patient presented to emergency for ocular discomfort, and the right globe was subsequently enucleated due to glaucoma and submitted for histopathology. Upon histopathologic evaluation, a uveal schwannoma was diagnosed and confirmed with immunohistochemical staining. Complete metastatic evaluation 1 and 6 months after initial presentation did not reveal evidence of metastasis, and the dog remains systemically healthy. This case represents a unique variant of uveal schwannoma and is relevant because although the vast majority of these tumors occur in blue-eyed dogs, clinicians should not completely rule out this tumor as a differential based on the iris color. [ABSTRACT FROM AUTHOR]

Objective To report 14 neoplasia-free feline eyes enucleated for suspected intraocular neoplasia containing only iridociliary cysts. To analyze clinical findings that may have led veterinarians to suspect neoplasia in these globes. Procedures The archives at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were searched to identify neoplasia-free feline globes enucleated for suspected neoplasia. Clinical data were obtained from medical records, veterinarian surveys, and COPLOW submission forms. All samples were examined grossly and histologically. Results All eyes were free of neoplasia and contained one or more iridociliary cysts. Nine of 14 globes were enucleated by or based on the recommendation of a boardcertified veterinary ophthalmologist. In eight of 14 cases, the submitting clinician listed melanoma as the only suspected diagnosis; in six of 14 cases, 'tumor' or 'mass' was listed. Clinical examination revealed a darkly pigmented intraocular mass in 11 of 14 cases. The mass was clinically perceived to be within the iris in seven of 14 cases. When examined histologically, 11 of 14 eyes contained multiple cysts, 13 of 14 contained multiloculated cysts, eight of 14 had a hyperplastic iris pigmented epithelium or cysts with thick black walls, and five of 14 had cysts prolapsed into the anterior chamber. Conclusions Although most iridociliary cysts in cats are easily diagnosed on clinical examination, a subset may be mistaken for neoplasia. In cases of suspected iris melanoma, iridociliary cysts should be considered as a differential diagnosis, especially if a mass appears to emanate from behind the iris, dyscoria is present, or if similar changes are noted in the contralateral eye. [ABSTRACT FROM AUTHOR]

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection. [ABSTRACT FROM AUTHOR]

Objective To present a description and categorization of the histopathological lesions in avian ocular trauma. Animal studied Seventy-five birds diagnosed with ocular trauma at to the Comparative Ocular Pathology Laboratory of Wisconsin. Procedures Histological slides were reviewed, and the type of trauma was classified by cause into either (i) blunt trauma or (ii) penetrating trauma and by duration into (i) acute or (ii) chronic. Results Blunt trauma was the most common source of trauma, and the most frequent lesions were observed in the retina (91%), with 71% of retinas having a tear or detachment and 46% of retinas showing chronic degenerative changes. Damage to the iris/ciliary body was present in 77% of cases. Corneal (17%) and lens (31%) lesions were relatively low. Acute traumatic events had a higher prevalence of readily identifiable discrete retinal tears/detachments (64%). Nearly all cases of chronic trauma exhibited chronic retinal lesions (93.7%), as well as a greater percentage of cartilage/bone lesions (71.4%), irido/cyclodialysis (51.9%), lenticular lesions (72.7%), and corneal damage (83.3%). However, the incidence of iridocyclodialysis was roughly equivalent for acute and chronic blunt trauma. Conclusions Ocular trauma can lead to profound acute and chronic lesions within the eye. Here, we provide insight into understanding ocular damage caused by trauma, which may help future studies suggest new therapeutic options and provide insight regarding the releasability of avian wildlife. [ABSTRACT FROM AUTHOR]

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10–12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated. [ABSTRACT FROM AUTHOR]

Purpose To describe the clinical and histopathologic features of glaucoma associated with Descemet's membrane ( DM) detachment in five horses without prior history of intraocular surgery. Animals studied Three Appaloosa horses and two Thoroughbreds were included in this study. The affected horses ranged in age from 16 to 27 years and presented with severe diffuse corneal edema. Procedure Five eyes were enucleated due to intraocular hypertension and/or chronic corneal ulceration. The enucleated globes were evaluated by the Comparative Ocular Pathology Laboratory of Wisconsin ( COPLOW). Each globe was routinely processed for histopathology and analyzed by light microscopy. A histologic diagnosis of glaucoma was reached by demonstrating a loss of optic nerve axonal tissue by measuring neurofilament-immunopositive axons with automated image analysis software. Results All five horses presented with unilateral severe diffuse corneal edema that had developed between 2 and 16 weeks prior to enucleation. Intraocular pressures for the affected eyes were between 9 and 87 mmHg prior to enucleation. Descemet's membrane detachment was identified histopathologically in all five globes (5/5, 100%). All five eyes had an avascular spindle cell proliferation filling the space between the displaced peripheral DM and the corneal stroma. Neurofilament immunostaining revealed axonal loss consistent with glaucoma. Conclusion Equine glaucoma may be associated with Descemet's membrane detachment. This detachment and glaucoma is a possible differential diagnosis for severe equine corneal edema. In this case series, an eye with a DM detachment had a poor prognosis for retention. [ABSTRACT FROM AUTHOR]

The 2015 Annual National Toxicology Program Satellite Symposium, entitled “Pathology Potpourri” was held in Minneapolis, Minnesota, at the American College of Veterinary Pathologists/American Society for Veterinary Clinical Pathology/Society of Toxicologic Pathology combined meeting. The goal of this symposium is to present and discuss diagnostic pathology challenges or nomenclature issues. Because of the combined meeting, both laboratory and domestic animal cases were presented. This article presents summaries of the speakers’ talks, including challenging diagnostic cases or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included hepatocellular lesions, a proposed harmonized diagnostic approach to rat cardiomyopathy, crop milk in a bird, avian feeding accoutrement, heat exchanger in a tuna, metastasis of a tobacco carcinogen–induced pulmonary carcinoma, neurocytoma in a rat, pituicytoma in a rat, rodent mammary gland whole mounts, dog and rat alveolar macrophage ultrastructure, dog and rat pulmonary phospholipidosis, alveolar macrophage aggregation in a dog, degenerating yeast in a cat liver aspirate, myeloid leukemia in lymph node aspirates from a dog, Trypanosoma cruzi in a dog, solanum toxicity in a cow, bovine astrovirus, malignant microglial tumor, and nomenclature challenges from the Special Senses International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Group. [ABSTRACT FROM AUTHOR]

Purpose To examine a series of 14 cases of canine ocular protothecosis from archived cases from the Comparative Ocular Pathology Laboratory of Wisconsin ( COPLOW), and compare gross and histologic findings. Methods Archival records from COPLOW were searched for canine cases of ocular protothecosis. Fourteen cases that contained matching criteria were identified, and gross and histologic findings, and clinical records for each case were tabulated, examined, and compared (2001-2013). Results Of the 14 cases identified, six had evidence of systemic disease, as per clinical history. Two of the 14 cases had Prototheca identified via cytology of ocular fluid or retinal exudate; in the remainder of cases, Prototheca identified via cytology of ocular fluid or retinal exudate in the remaining 12 cases, Prototheca was identified upon histologic examination of the submitted globe(s). Presenting ocular clinical signs were variable and nonspecific. Duration of ocular clinical signs varied from days to months. Fundoscopically, white membranes or plaques were identified on or around the retina in five cases. Retinal detachment was identified in 13 of the 14 submitted globes on gross examination following fixation and sectioning. The predominant histologic finding was granulomatous chorioretinitis with retinal detachment, with variable numbers of Prototheca within the inflammatory infiltrate. Conclusions Due to the nonspecific nature of the ocular signs, a diagnosis of protothecosis generally is not made until enucleation and histopathologic examination of the globe(s). Retinal detachment and blindness were common. Cytologic sampling of retinal plaques and exudate may provide a rapid way to identify Prototheca. [ABSTRACT FROM AUTHOR]

Following unilateral enucleation, 4 Domestic Shorthair cats with an average age of 12.5 years (range: 9–16 years) were histologically diagnosed with a presumed primary intraocular chondrosarcoma at the Comparative Ocular Pathology Laboratory of Wisconsin (Madison, Wisconsin). Medical records and follow-up were available for 3 of the 4 cats. Clinically, only 1 eye was affected in each cat; a mass lesion was noted in 2 cats, and a neoplasm was suspected in the other 2 cats. Grossly, 3 tumors presented as coalescing, poorly demarcated, white, friable masses filling the vitreous and intraocular chambers; 1 tumor presented as a solitary, well-demarcated, tan mass involving the iris and ciliary body. Histologically, all 4 neoplasms were composed of haphazardly arranged plump neoplastic spindle cells surrounded by irregular islands and thick trabeculae of abundant, variably basophilic, and Alcian blue–positive chondromatous matrix. None of the cats presented histologically or clinically with signs suggestive of feline posttraumatic ocular sarcoma. Two cats are still alive and healthy 6 months and 3 years following enucleation. One cat died 6 months following enucleation; however, this cat suffered from poorly controlled diabetes mellitus, and the cause of death is undetermined. No other tumors or skeletal lesions were identified that could suggest a metastatic tumor to the eye. The origin of primary intraocular chondrosarcoma is unclear, but is presumed to be ocular multipotent mesenchymal stem cells. Four cases of intraocular chondrosarcoma in cats not associated with the posttraumatic sarcoma complex of intraocular tumors are described. [ABSTRACT FROM PUBLISHER]

Cutaneous meningiomas are rare tumors in human beings and animals. Two canine cases of cutaneous meningiomas affecting the eyelid are described in the current study: the first from a 5-week-old female Springer Spaniel dog with an 8 cm in diameter congenital mass expanding the left upper eyelid and medial canthus; the second from a 10-year-old female spayed Maltese–Poodle mix dog with 3 firm subcutaneous nodules affecting the right upper eyelid. All masses were removed surgically. Histologically, tumors were composed of spindle-to-epithelioid cells arranged in small lobules forming solid concentric whorls. Neoplastic cells were positive for vimentin and S100 and negative for pancytokeratin, glial fibrillar acid protein, and neurofilament. Transmission electron microscopy revealed meningothelial cells with convoluted interdigitating processes, desmosomes, and hemidesmosomes, and moderate numbers of cytoplasmic microfilaments. None of the cases presented a primary neuroaxial meningioma. The first case presents clinicopathological features consistent with human type I (congenital) cutaneous meningioma. The second case is consistent with a type II (acquired ectopic) tumor, and both are hypothesized to arise from ectopic arachnoid cells displaced during development. [ABSTRACT FROM PUBLISHER]

s The excisional dorsal full-thickness skin wound model with or without splinting is widely utilized in wound healing studies using diabetic or normal mice. However, the effects of splinting on dermal wound healing have not been fully characterized, and there are limited data on the direct comparison of wound parameters in the splinted model between diabetic and normal mice. We compared full-thickness excisional dermal wound healing in db/db and heterozygous mice by investigating the effects of splinting, semi-occlusive dressing, and poly(ethylene glycol) treatment. Two 8-mm full-thickness wounds were made with or without splinting in db/db and heterozygous mice. Body weights, splint maintenance, wound contraction, wound closure, and histopathological parameters including reepithelialization, wound bed collagen deposition, and inflammation were compared between groups. Our results show that silicone splint application effectively reduced wound contraction in heterozygous and db/db mice. Splinted wounds, as opposed to nonsplinted wounds, exhibited no significant differences in wound closure between heterozygous and db/db mice. Finally, polyethylene glycol and the noncontact dressing had no significant effect on wound healing in heterozygous or db/db mice. We believe these findings will help investigators in selection of the appropriate wound model and data interpretation with fully defined parameters. [ABSTRACT FROM AUTHOR]

A formalin-fixed left, blue eye, from a 9-year-old, spayed female beagle dog was submitted to the Comparative Ocular Pathology Laboratory of Wisconsin ( COPLOW) for light microscopic evaluation. The history included glaucoma and an abnormal appearance for 6 months and then the development of a uveal mass. The histologic diagnosis was a spindle cell tumor of blue-eyed dogs ( SCTBED). In June of 2012, the dog was euthanized due to ailing health, and there was radiographic and postmortem examination evidence of neoplastic metastasis. This is the first reported case of this primary ocular neoplasm metastasizing, and we propose to rename SCTBED as a uveal schwannoma of blue-eyed dogs. [ABSTRACT FROM AUTHOR]

A captive, adult, male northern saw-whet owl (Aegolius acadicus) was examined for blepharospasm of the left eye. The owl was diagnosed with bilateral anterior uveitis and a corneal ulceration in the left eye. It was treated with oral and topical nonsteroidal anti-inflammatory medications and a topical antibiotic. Multiple recheck examinations and medication adjustments were performed over the next 4 months, at the end of which time the bilateral anterior uveitis was controlled with a topical nonsteroidal anti-inflammatory applied 3 times per week to both eyes. The owl was re-examined 2 months later after 2 suspected neurologic episodes. On physical examination, the owl was quiet and had difficulty standing and ambulating. Five firm multilobular and immobile masses were identified overlying the pectoral muscle and sternum. Fine-needle aspiration from 1 mass revealed neoplastic cells consistent with a sarcoma. The owl was euthanatized. On the basis of results of histopathologic examination, the mass was diagnosed as a pleomorphic spindle cell sarcoma with features of rhabdomyosarcoma, liposarcoma, and osteosarcoma. Numerous tumor cells were immunopositive for myoglobin and desmin, indicating striated muscle origin. Although a metastatic lesion was present in 1 adrenal gland, lesions of inflammation or neoplasia were absent in either eye on histopathologic examination. This report describes an apparent ocular manifestation of systemic disease in an avian species with clinically diagnosed recurrent anterior uveitis. [ABSTRACT FROM AUTHOR]

Purpose: To characterize early trabecular meshwork (TM) morphologic abnormalities in a feline model of human primary congenital glaucoma (PCG) caused by mutation in LTBP2., Methods: Eyes from 41 cats, including 19 normal and 22 homozygous for LTBP2 mutation, across various postnatal stages (birth, 2 weeks, 5 weeks, and 12 weeks) were paraformaldehyde fixed, anterior segments dissected, post-fixed in glutaraldehyde, osmicated, and processed and sectioned for transmission electron microscopy. Cell morphology, nuclear shape, and intertrabecular space (ITS) were quantitatively assessed, and the structure of the fibrillar extracellular matrix in the TM was systematically evaluated., Results: The earliest differences in TM morphology between PCG and normal cats were identified at 2 weeks postnatally. Elastic fibers in the TM were discontinuous and disorganized (P = 0.0122), and by 5 weeks of age PCG cats presented significantly less ITS (P = 0.0076) and morphologically rounder TM cells than normal cats (P = 0.0293). By 12 weeks of age, the ITS was further collapsed (P < 0.0001), and the TM cells were morphologically elongated and attenuated in PCG compared to controls (P = 0.0028)., Conclusions: In this feline model of PCG due to LTBP2 mutation, development of ultrastructural TM extracellular matrix abnormalities are first observed by 2 weeks and cellular abnormalities by 5 weeks of age. By 12 weeks of age, when intraocular pressure becomes significantly elevated, the TM morphologic abnormalities are already well established. These findings suggest that the postnatal period between 0 and 5 weeks of age is critical for TM and PCG development and progression in cats.

Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluated changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley rats were fed a high-fat diet (45% fat) or normal diet, and rats fed the high-fat diet were injected with streptozotocin intraperitoneally to generate a model of T2DM. Cataract formation and corneal endothelial cell density were assessed using microscopic analysis. Diabetes-related rat aqueous humor alterations were assessed using metabolomics screening. Transmission electron microscopy was used to assess qualitative ultrastructural changes ciliary process microvessels at the site of aqueous formation in the eyes of diabetic rats and humans. Eyes from the diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes, including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. These results support the use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. All rights reserved.)

In collaboration with the American College of Veterinary Pathologists.

The lamina cribrosa (LC) region of the optic nerve head (ONH) is considered a primary site for glaucomatous damage. In humans, biology of this region reflects complex interactions between retinal ganglion cell (RGC) axons and other resident ONH cell-types including astrocytes, lamina cribrosa cells, microglia and oligodendrocytes, as well as ONH microvasculature and collagenous LC beams. However, species differences in the microanatomy of this region could profoundly impact efforts to model glaucoma pathobiology in a research setting. In this study, we characterized resident cell-types, ECM composition and ultrastructure in relation to microanatomy of the ONH in adult domestic cats (Felis catus). Longitudinal and transverse cryosections of ONH tissues were immunolabeled with astrocyte, microglia/macrophage, oligodendrocyte, LC cell and vascular endothelial cell markers. Collagen fiber structure of the LC was visualized by second harmonic generation (SHG) with multiphoton microscopy. Fibrous astrocytes form glial fibrillary acidic protein (GFAP)-positive glial columns in the pre-laminar region, and cover the collagenous plates of the LC region in lamellae oriented perpendicular to the axons. GFAP-negative and alpha-smooth muscle actin-positive LC cells were identified in the feline ONH. IBA-1 positive immune cells and von Willebrand factor-positive blood vessel endothelial cells are also identifiable throughout the feline ONH. As in humans, myelination commences with a population of oligodendrocytes in the retro-laminar region of the feline ONH. Transmission electron microscopy confirmed the presence of capillaries and LC cells that extend thin processes in the core of the collagenous LC beams. In conclusion, the feline ONH closely recapitulates the complexity of the ONH of humans and non-human primates, with diverse ONH cell-types and a robust collagenous LC, within the beams of which, LC cells and capillaries reside. Thus, studies in a feline inherited glaucoma model have the potential to play a key role in enhancing our understanding of ONH cellular and molecular processes in glaucomatous optic neuropathy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the safety and tolerability of a microsphere thermo-responsive hydrogel drug delivery system (DDS) loaded with aflibercept in a nonhuman primate model., Methods: A sterile 50 µL of aflibercept-loaded microsphere thermo-responsive hydrogel-DDS (aflibercept-DDS) was injected intravitreally into the right eye of 10 healthy rhesus macaques. A complete ophthalmic examination, intraocular pressure (IOP) measurement, fundus photography, spectral-domain optical coherence tomography (SD-OCT), and electroretinogram were performed monthly for 6 months. One macaque was euthanized monthly, and the enucleated eyes were submitted for measurement of bioactive aflibercept concentrations. Four eyes were submitted for histopathology., Results: Injected aflibercept-DDS was visualized in the vitreous until 6 months postinjection. No abnormalities were observed in the anterior segment, and IOP remained within normal range during the study period. A small number of cells were observed in the vitreous of some macaques, but otherwise the remainder of the posterior segment examination was normal. No significant changes in retinal architecture or function as assessed by SD-OCT and histology or full-field electroretinography, respectively, were observed. A mild, focal foreign body reaction around the injectate was observed with histology at 6 months postinjection. A mean of 2.1 ng/µL of aflibercept was measured in the vitreous., Conclusions: Intravitreally injected aflibercept-DDS achieved controlled, sustained release of aflibercept with no adverse effects for up to 6 months in the eyes of healthy rhesus macaques., Translational Relevance: Aflibercept-DDS may be a more effective method to deliver bioactive antivascular endothelial growth factor agents than current practice by reducing the frequency of intravitreal injections and providing controlled drug release., Competing Interests: Disclosure: S. Kim, None; J.J. Kang-Mieler, microsphere thermo-responsive drug delivery system (P); W. Liu, None; Z. Wang, None; G. Yiu, None; L.B.C. Teixeira, None; W.F. Mieler, None; S.M. Thomasy, None, (Copyright 2020 The Authors.)