Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye.

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.

Clinicopathologic profiles of canine ocular melanosis: A comparative study between cairn terriers and non-cairn terriers.

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.

Collagen crosslinking impacts stromal wound healing and haze formation in a rabbit phototherapeutic keratectomy model.

Purpose: The purpose of this study was to evaluate the elastic modulus, keratocyte-fibroblast-myocyte transformation, and haze formation of the corneal stroma following combined phototherapeutic keratectomy (PTK) and epithelium-off UV-A/riboflavin corneal collagen crosslinking (CXL) using an in vivo rabbit model. Methods: Rabbits underwent PTK and CXL, PTK only, or CXL 35 days before PTK. Rebound tonometry, Fourier-domain optical coherence tomography, and ultrasound pachymetry were performed on days 7, 14, 21, 42, 70, and 90 post-operatively. Atomic force microscopy, histologic inflammation, and immunohistochemistry for α-smooth muscle actin (α-SMA) were assessed post-mortem. Results: Stromal haze formation following simultaneous PTK and CXL was significantly greater than in corneas that received PTK only and persisted for more than 90 days. No significant difference in stromal haze was noted between groups receiving simultaneous CXL and PTK and those receiving CXL before PTK. Stromal inflammation did not differ between groups at any time point, although the intensity of α-SMA over the number of nuclei was significantly greater at day 21 between groups receiving simultaneous CXL and PTK and those receiving CXL before PTK. The elastic modulus was significantly greater in corneas receiving simultaneous CXL and PTK compared with those receiving PTK alone. Conclusions: We showed that stromal haze formation and stromal stiffness is significantly increased following CXL, regardless of whether it is performed at or before the time of PTK. Further knowledge of the biophysical cues involved in determining corneal wound healing duration and outcomes will be important for understanding scarring following CXL and for the development of improved therapeutic options.

Iridial melanocytoma in a ferruginous hawk (Buteo regalis): A case report and review of avian melanocytic neoplasia.

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.

Clinical and histopathological features of proliferative corneal lesions in Cyprininae fishes: Implications for treatment and insights into corneal tumors.

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.

Atypical chorioretinal lesions in Siberian Husky dogs with primary angle-closure glaucoma: a case series.

BACKGROUND: A number of etiologies for different canine chorioretinal lesions have been proved or suggested but some fundic lesions remain unclear in terms of an etiologic diagnosis, treatment options and prognosis. The purpose of this case series is to describe atypical chorioretinal lesions observed in dogs with primary angle-closure glaucoma (PACG). CASE PRESENTATION: Two spayed-female Siberian Huskies (3- and 4-year-old) and one Siberian Husky/Australian Shepherd mixed breed dog (11-month-old) that had multifocal depigmented retinal lesions and PACG were included. PROCEDURES: Ophthalmic examination, gross, and histopathologic examination findings are described. One of the dogs underwent further clinical diagnostics. Advanced clinical diagnostics on the fellow, presumed to be non-glaucomatous eye of a dog revealed: pectinate ligament dysplasia by gonioscopy, retinal thinning in the depigmented area and wedge shaped retinal thinning with delayed choroidal vascular perfusion by optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein and indocyanine green angiography. Quantifiable maze testing for the same eye revealed mild nyctalopia but the full-field electroretinogram showed no generalized decrease of retinal function. Genetic testing for mutations within the retinitis pigmentosa GTPase regulator gene causing X-linked progressive retinal atrophy in Siberian Huskies was negative. Histopathologic evaluations on enucleated eyes in two dogs confirmed goniodysgenesis, PACG with optic nerve head cupping, and diffuse inner retinal atrophy. In addition, segmental profound retinal atrophy, loss of retinal pigment epithelium, and adhesion of the retina to Bruch's membrane was observed and coincided with multifocal depigmented lesions noted on fundic examination. CONCLUSIONS: To our knowledge, this is the first case series with clinical and histopathologic data of chorioretinal lesions, most likely caused by severely impaired choroidal perfusion. Further studies are warranted to elucidate the etiology and pathophysiology, including its possible association with PACG.

Development and validation of methods to visualize conventional aqueous outflow pathways in canine primary angle closure glaucoma.

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.

Clinical and pathologic evaluation of chorioretinal lesions in wild owl species.

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.

Mapping retinal ganglion cell somas in a large-eyed glaucoma model.

Purpose: The purpose of this study was to identify a robust, representative region of interest (ROI) for studies of retinal ganglion cell (RGC) soma loss in feline congenital glaucoma (FCG), a spontaneous, large-eyed glaucoma model. Methods: Seven FCG and three wild-type (wt) eyes were collected from 10 adult cats of both sexes. Eyes enucleated postmortem were immediately fixed overnight in 4% paraformaldehyde and then stored in 0.1 M PBS at 4 °C. The retinas were wholemounted, Nissl stained with cresyl violet, and imaged using light microscopy. Somas of RGCs were manually identified according to long-established morphological criteria and quantified using a semiautomated method; their coordinates were used to create density maps and plots of the retinal topography. The RGC axon counts for the corresponding eyes were obtained from glutaraldehyde-fixed, resin-embedded optic nerve cross-sections stained with 0.1% p-phenylenediamine (PPD) using a semiautomated counting method. Correlations between total optic nerve axons and RGC soma counts were assessed by linear regression. A k-means cluster algorithm was used to identify a retinal ROI, with further definition using a probability density algorithm. Results: Interindividual variability in RGC total soma counts was more pronounced in FCG cats (mean = 83,244, range: 0-155,074) than in wt cats (mean = 117,045, range: 97,373-132,972). In general, RGC soma counts were lower in FCG cats than they were in wt cats. RGC axon counts in the optic nerve cross-sections were lower than, but strongly correlated to, the total RGC soma count across all cats (in wt and FCG retinas; R2 = 0.88) and solely FCG eyes (R2 = 0.92). The k-means cluster algorithm indicated a region of the greatest mean difference between the normal wt retinas and FCG-affected retinas within the temporal retina, incorporating the region of the area centralis. Conclusions: As in other species, RGC soma count and topography are heterogeneous between individual cats, but we identified an ROI in the temporal retina for future studies of RGC soma loss or preservation in a large-eyed model of congenital glaucoma. Many of the methods refined and established to facilitate studies in this FCG model will be broadly applicable to studies in other large-eyed models.

Microstructure and resident cell-types of the feline optic nerve head resemble that of humans.

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.

Ocular porcupine quilling in dogs: Gross, clinical and histopathologic findings in 17 cases (1986-2018).

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.

Atypical free-floating iridociliary pigmented epithelial cysts and secondary glaucoma in a caiman (Caiman latirostris).

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.

Prophylactic anti-glaucoma therapy in dogs with primary glaucoma: A practitioner survey of current medical protocols.

AIM: To examine the use of prophylactic anti-glaucoma medications in the normotensive fellow eye in dogs with unilateral overt primary glaucoma by veterinary ophthalmology clinicians. METHODS: A survey of veterinary ophthalmology clinicians was distributed over two international list serves servicing veterinary ophthalmologists, trainees, and individuals whose practice consisted primarily of ophthalmic patients. The survey was developed following analysis of historical and currently available medical options for control of intraocular pressure and for neuroprotection. RESULTS: Responses from 199 veterinary ophthalmology clinicians were evaluated. While a large variety of topical anti-hypertensive drugs and protocols were used, the most commonly used medications were aqueous humor production suppressors such as dorzolamide 2.0% ophthalmic solution, timolol 0.5% ophthalmic solution, and a combination product containing both drugs. Latanoprost 0.005% ophthalmic solution was used infrequently for prophylaxis by comparison. The majority of respondents do not use concurrent anti-inflammatory medications (61.22%), although a sizeable minority used prednisolone acetate, dexamethasone, or ketorolac as prophylactic treatment. Systemically administered ocular anti-hypertensive agents were rarely used. Only 40% of respondents used neuroprotectant agents; the most commonly prescribed were the calcium channel blocker amlodipine and the nutraceutical Ocu-Glo™. Recommended intervals between re-examination by the clinician ranged from one month to one year, with most re-evaluations occurring every 3 to 6 months. The majority of respondents recommended more frequent assessments of IOP at intervals between once monthly and once every 3 months. CONCLUSIONS: Data analysis of medical therapy for the normotensive fellow eye of dogs previously diagnosed with primary glaucoma suggests that there is a great need for well-designed, prospective, controlled, multi-center studies to determine which protocols have the greatest efficacy in delaying an overt attack in the previously normotensive eye in dogs with a genetic predisposition to glaucoma. Prospective studies utilizing a carbonic anhydrase inhibitor such as dorzolamide and a prostaglandin analogue such as latanoprost would be reasonable as these two drugs are widely used in the treatment of overt glaucoma and would allow for an exploration of the impact of different mechanisms of action of lowering IOP on the pathophysiology of primary glaucoma.

A clinicopathological study of 17 cases of ocular surface xanthogranuloma in dogs.

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.

Cactus-induced keratoconjunctivitis in Texas: A case series of three dogs and one cat.

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.

Clinical and histopathological classification of feline intraocular lymphoma.

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.

Management of corneal epithelial defects in a population of mature chuck-will's-widows (Antrostomus carolinensis) in South Florida.

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.

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.

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.

Ocular phenotypic consequences of a single copy deletion of the Yap1 gene (Yap1 +/-) in mice.

Purpose: To identify the effects of a single copy deletion of Yap1 (Yap1 +/-) in the mouse eye, the ocular phenotypic consequences of Yap1 +/- were determined in detail. Methods: Complete ophthalmic examinations, as well as corneal esthesiometry, the phenol red thread test, intraocular pressure, and Fourier-domain optical coherence tomography were performed on Yap1 +/- and age-matched wild-type (WT) mice between eyelid opening (2 weeks after birth) and adulthood (2 months and 1 year after birth). Following euthanasia, enucleated eyes were characterized histologically. Results: Microphthalmia with small palpebral fissures, corneal fibrosis, and reduced corneal sensation were common findings in the Yap1 +/- mice. Generalized corneal fibrosis precluded clinical examination of the posterior structures. Histologically, thinning and keratinization of the corneal epithelium were observed in the Yap1 +/- mice in comparison with the WT mice. Distorted collagen fiber arrangement and hypercellularity of keratocytes were observed in the stroma. Descemet's membrane was extremely thin and lacked an endothelial layer in the Yap1 +/- mice. The iris was adherent to the posterior cornea along most of its surface creating a distorted contour. Most of the Yap1 +/- eyes were microphakic with swollen fibers and bladder cells. The retinas of the Yap1 +/- mice were normal at 2 weeks and 2 months of age, but the presence of retinal abnormalities, including retinoschisis and detachment, was markedly increased in the Yap1 +/- mice at 1 year of age. Conclusions: The results show that the heterozygous deletion of the Yap1 gene in mice leads to complex ocular abnormalities, including microphthalmia, corneal fibrosis, anterior segment dysgenesis, and cataract.

In vivo confocal microscopy characteristics of equine epithelial and subepithelial nonulcerative keratomycosis.

OBJECTIVE: To describe the in vivo confocal microscopy features of horses with epithelial and subepithelial nonulcerative keratomycosis. ANIMALS STUDIED: Four horses with a clinical diagnosis of epithelial or subepithelial keratomycosis. PROCEDURES: Horses were examined on one or more occasions by in vivo laser scanning confocal microscopy of the cornea. Confocal microscopic examination characteristics were correlated with clinical, cytological, and histopathological findings for the horses. RESULTS: All horses had an irregular corneal epithelial surface during slit-lamp biomicroscopy examination. Epithelial or subepithelial corneal opacities were present in multifocal or diffuse patterns. Positive rose bengal corneal staining was present focally or diffusely in all cases. Fungal hyphae were detected in cytological or histopathological corneal samples from all horses. Aspergillus, Fusarium, and Penicillium spp. were cultured from corneal samples. Confocal microscopy detected hyphae diffusely distributed over the axial cornea in horses with epithelial clinical disease. Fungal hyphae were present in all layers of the corneal epithelium and associated with disorganized and sloughing epithelial cells with minimal leukocytes. Subepithelial keratomycosis was correlated with focal, dense accumulations of hyphae in the immediate subepithelial anterior stroma that were surrounded by moderate numbers of leukocytes. Two horses were examined by confocal microscopy on multiple occasions during the course of medical therapy, and fungal hyphae were observed to migrate from the epithelium into the subepithelial stroma as the clinical corneal disease progressed. CONCLUSIONS: With in vivo confocal microscopy, both epithelial and subepithelial keratomycosis appear as unique clinical entities. Equine epithelial keratomycosis is a potential precursor to subepithelial keratomycosis.