Leandro B. C. Teixeira

Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy primarily caused by mutations in OPA1 . We identified and defined a spontaneous nonhuman primate (NHP) model of ADOA using rhesus macaques heterozygous for a missense mutation ( OPA1 A8S). With ocular examinations, ophthalmic imaging, electroretinography, histopathology, immunohistochemistry, and transmission electron microscopy (TEM), we documented retinal nerve fiber layer (RNFL) thinning, retinal ganglion cell (RGC) loss and dysfunction, OPA1 mislocalization, and reduced axonal mitochondrial density in affected macaques. Our investigation revealed substantial phenotypic variability among affected macaques, shedding light on the pathogenesis of ADOA. The retinas were evaluated using techniques such as spectral-domain optical coherence tomography and fundus photography facilitating observation of structural changes in the retina and optic nerve. Thinning of the RNFL and optic nerve head degeneration, hallmark features of ADOA, were observed in affected macaques. Decreased RGC function in the OPA1 heterozygotes was demonstrated with pattern electroretinography. Histopathological analysis and immunohistochemical staining of postmortem retinal tissue suggested RGC loss in the papillomacular bundle, with reduced OPA1 and mitochondria in the RGC axons, indicating dysfunctional mitochondrial dynamics and reduced function consistent with ADOA. Ultrastructural changes were evident with TEM including dysmorphic mitochondria, axonal loss, myelin disruption, and hypertrophic astrocytic processes. The observed similar pattern of RGC loss and dysfunction coupled with phenotypic heterogeneity in our NHP model reflects the clinical variability observed in human ADOA patients indicating that therapeutic interventions in this foveate model will likely translate to the human condition.

Dogs with sudden acquired retinal degeneration syndrome (SARDS) have rapid onset visual dysfunction and subsequent outer retinal atrophy. The pathophysiology of SARDS is poorly understood. This study’s objective was to examine the histologic features of choriocapillaris perfusion and Bruch’s membrane morphology in eyes from dogs with SARDS. Archived, paraffin-embedded, sagittal eye sections of dogs with SARDS ( n = 12), age/breed-matched healthy control dogs ( n = 24), and age-matched dogs with progressive retinal atrophy (PRA, n = 12) were evaluated. Choriocapillaris density and patency were estimated using light microscopy and immunofluorescence to quantify patent vessels containing luminal erythrocytes and nonpatent vessels with empty lumens. The outer nuclear layer (ONL) nuclei density was quantified to determine the extent of atrophy. The thickness of Bruch’s membrane was measured from transmission electron microscopy images ( n = 5 SARDS, 5 PRA, 6 controls). Statistical analyses were performed using 1-way analysis of variance (ANOVA) and the Spearman rank correlation. Both SARDS and PRA samples had lower patent vessel densities compared with controls ( P = .006 and .04, respectively). ONL nuclei density and choriocapillaris vessel density were associated in samples from dogs with PRA ( r = 0.94–1.00, P < .05), but not SARDS ( r = 0.14–0.66, P > .05). Eyes with SARDS had thicker Bruch’s membrane than controls and dogs with PRA ( P < .0001). Outer retinal disorders in dogs, including SARDS and PRA, are associated with alterations in choriocapillaris characteristics and Bruch’s membrane thickness. Whether these findings are causative or correlative with disease is unknown.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project ( www.toxpath.org/ inhand.asp) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying lesions observed in ocular tissues (eyes and glands and ocular adnexa) from laboratory nonrodent species (rabbits, dogs, minipigs, and nonhuman primates) used in nonclinical safety studies with an emphasis on ocular-targeted dosing. Some of the lesions are illustrated by color photomicrographs. The standardized nomenclature presented in this document is also available electronically on the Internet ( http://www.goreni.org/ ). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes descriptions and visual depictions of spontaneous lesions and lesions induced by exposure to various test materials. A widely accepted and utilized internationally harmonized nomenclature for lesions in laboratory animals will provide a common language among regulatory and scientific research organizations in different countries and increase and enrich international exchanges of information among toxicologists and pathologists.

An approximately 26‐year‐old, suspected female, red‐tailed hawk (Buteo jamaicensis) was presented with a history of chronic ocular changes of the left eye likely secondary to blunt trauma resulting in blindness and phthisis bulbi. Ophthalmic evaluation of OS revealed a large intraocular mass, 3+ aqueous flare indicating anterior uveitis, and severely decreased intraocular pressure measuring 5 mmHg. Ocular ultrasound revealed an abnormal, spherical shaped and hyperechoic lens, as well as hyperechoic material or a mass lesion in the posterior segment. An enucleation procedure was performed, and histopathology of the eye revealed no signs of neoplasia but instead intraocular osseous metaplasia with bone marrow and adipose tissue replacing the lens. Similar mass lesions were found in the retina and choroid. Multiple fractures in the scleral ossicle and cartilage correlated the intraocular lesions with a blunt traumatic event. A bioresorbable disk of porcine small intestine submucosa (BioSIS Vetrix®) was incorporated to relieve tension during closure. The graft sloughed during healing process, revealing a healed wound underneath. The BioSIS was not incorporated into the wound as designed but may have facilitated healing. This is the first report of intraocular osseous metaplasia in a raptor and the use of BioSIS Vetrix® with enucleation in an avian species.

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.

Objectives: 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.

A 21‐year‐old, suspected female captive ferruginous hawk (Buteo regalis) was followed for 3 years due to an iridial mass of the left eye (OS) that progressively increased in size. Enucleation of OS was eventually recommended due to the iridial mass taking up approximately 75% of the anterior chamber, and the bird seemed less active. A complete physical examination, complete blood cell count, biochemistry, and survey radiographs were performed pre‐surgery with no findings indicating metastasis. A subconjunctival enucleation was performed and the globe was submitted for histopathology through the Comparative Ocular Pathology Lab of Wisconsin. The histopathologic evaluation determined the mass to be consistent with an iris melanocytoma, which has not been previously reported in this species. The patient recovered well from surgery and has remained comfortable and active for 117 days post‐surgery. This case report aimed to review the current available information on avian ocular neoplasms as well as describe the clinical presentation, medical management and surgical procedure, and long‐term follow‐up for this patient to enhance clinical understanding of the behavior of iris melanocytic tumors in avian species.

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.

Sebaceous carcinomas of the human ocular adnexa commonly exhibit pagetoid spread, mutations in tumor-suppressor genes, and protooncogene copy number gain. Sebaceous carcinomas are rarely reported in other species, and while the Meibomian gland (MG) represents the most common ocular adnexal structure of the canine eyelid to develop neoplasia, most are clinically and histologically benign. The objective of this study was to compare molecular features of canine MG carcinomas and adenomas. Two retrospectively identified MG carcinomas were subject to immunohistochemistry and qPCR. When compared with normal glands, MYC was upregulated in benign and malignant MG neoplasms. Aberrant p53 expression was restricted to the nuclei of intraepithelial neoplastic cells in MG carcinomas. Adipophilin expression was diminished in MG neoplasms compared with the normal MG. Our findings, if confirmed in a larger cohort of cases, could suggest that MG oncogenesis in a dog may exhibit similar molecular features as their human counterparts.

In collaboration with the American College of Veterinary Pathologists