Parasiticide use and obesity in dogs with sudden acquired retinal degeneration syndrome.

OBJECTIVE: To investigate parasiticide use and describe signalment features in patients with sudden acquired retinal degeneration syndrome (SARDS). ANIMALS: Retrospective case-control study of dogs with (n = 71) and without (136) SARDS. METHODS: Parasiticide use, presentation season, weight, body condition, and signalment were compared between dogs diagnosed with SARDS and the reference population by use of descriptive statistics and logistic regression. RESULTS: Animals with SARDS were at a 5.99 times higher odds of having previously used imidacloprid (95% CI, 1.6 to 22.2; P = .003). However, time of last imidocloprid administration was > 6 years prior to diagnosis in 6 SARDS-affected individuals and 15, 26, or 42 months before diagnosis (n = 1 each). No other class of parasiticide had a significant association with SARDS. Seasonal variation was observed with a negative association identified between incidence of SARDS and tick season (October to January; P < .001). Overweight and obese dogs were 4.42 (95% CI, 1.9 to 10.4) and 4.96 (95% CI, 2.1 to 11.6) times more likely to have SARDS (P ≤ .001). History of polyphagia or weight gain was not associated with an increased likelihood of being overweight or obese within the SARDS-affected population (P > .108). CLINICAL RELEVANCE: While a statistically significant association was found between imidacloprid use and SARDS, this is unlikely to be clinically significant given the lack of a temporal association, sparse exposure numbers, and low point estimate of the OR. A positive association between being overweight or obese and a diagnosis of SARDS was found independent of polyphagia and weight gain, suggesting that it may be a risk factor for the development of SARDS.

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.

Andrographolide Inhibits Corneal Fibroblast to Myofibroblast Differentiation In Vitro.

Corneal opacification due to fibrosis is a leading cause of blindness worldwide. Fibrosis occurs from many causes including trauma, photorefractive surgery, microbial keratitis (infection of the cornea), and chemical burns, yet there is a paucity of therapeutics to prevent or treat corneal fibrosis. This study aimed to determine if andrographolide, a labdane diterpenoid found in Andrographis paniculate, has anti-fibrotic properties. Furthermore, we evaluated if andrographolide could prevent the differentiation of fibroblasts to myofibroblasts in vitro, given that the transforming growth factor beta-1(TGF-ß1) stimulated persistence of myofibroblasts in the cornea is a primary component of fibrosis. We demonstrated that andrographolide inhibited the upregulation of alpha smooth muscle actin (αSMA) mRNA and protein in rabbit corneal fibroblasts (RCFs), thus, demonstrating a reduction in the transdifferentiation of myofibroblasts. Immunofluorescent staining of TGF-ß1-stimulated RCFs confirmed a dose-dependent decrease in αSMA expression when treated with andrographolide. Additionally, andrographolide was well tolerated in vivo and had no impact on corneal epithelialization in a rat debridement model. These data support future studies investigating the use of andrographolide as an anti-fibrotic in corneal wound healing.

Cytotoxicity of 2D engineered nanomaterials in pulmonary and corneal epithelium.

Two-dimensional (2D) engineered nanomaterials are widely used in consumer and industrial goods due to their unique chemical and physical characteristics. Engineered nanomaterials are incredibly small and capable of being aerosolized during manufacturing, with the potential for biological interaction at first-contact sites such as the eye and lung. The unique properties of 2D nanomaterials that make them of interest to many industries may also cause toxicity towards epithelial cells. Using murine and human respiratory epithelial cell culture models, we tested the cytotoxicity of eight 2D engineered nanomaterials: graphene (110 nm), graphene oxide (2 um), graphene oxide (400 nm), reduced graphene oxide (2 um), reduced graphene oxide (400 nm), partially reduced graphene oxide (400 nm), molybdenum disulfide (400 nm), and hexagonal boron nitride (150 nm). Non-graphene nanomaterials were also tested in human corneal epithelial cells for ocular epithelial cytotoxicity. Hexagonal boron nitride was found to be cytotoxic in mouse tracheal, human alveolar, and human corneal epithelial cells. Hexagonal boron nitride was also tested for inhibition of wound healing in alveolar epithelial cells; no inhibition was seen at sub-cytotoxic doses. Nanomaterials should be considered with care before use, due to specific regional cytotoxicity that also varies by cell type. Supported by U01ES027288 and T32HL007013 and T32ES007059.

Retinal organoids derived from rhesus macaque iPSCs undergo accelerated differentiation compared to human stem cells.

PURPOSE: To compare the timing and efficiency of the development of Macaca mulatta, a nonhuman primate (NHP), induced pluripotent stem cell (rhiPSC) derived retinal organoids to those derived from human embryonic stem cells (hESCs). RESULTS: Generation of retinal organoids was achieved from both human and several NHP pluripotent stem cell lines. All rhiPSC lines resulted in retinal differentiation with the formation of optic vesicle-like structures similar to what has been observed in hESC retinal organoids. NHP retinal organoids had laminated structure and were composed of mature retinal cell types including cone and rod photoreceptors. Single-cell RNA sequencing was conducted at two time points; this allowed identification of cell types and developmental trajectory characterization of the developing organoids. Important differences between rhesus and human cells were measured regarding the timing and efficiency of retinal organoid differentiation. While the culture of NHP-derived iPSCs is relatively difficult compared to that of human stem cells, the generation of retinal organoids from NHP iPSCs is feasible and may be less time-consuming due to an intrinsically faster timing of retinal differentiation. CONCLUSIONS: Retinal organoids produced from rhesus monkey iPSCs using established protocols differentiate through the stages of organoid development faster than those derived from human stem cells. The production of NHP retinal organoids may be advantageous to reduce experimental time for basic biology studies in retinogenesis as well as for preclinical trials in NHPs studying retinal allograft transplantation.

Host Immune Responses after Suprachoroidal Delivery of AAV8 in Nonhuman Primate Eyes.

The suprachoroid is a potential space located between the sclera and choroid of the eye, which provides a novel route for ocular drug or viral vector delivery. Suprachoroidal injection of adeno-associated virus (AAV)8 using transscleral microneedles enables widespread transgene expression in eyes of nonhuman primates, but may cause intraocular inflammation. We characterized the host humoral and cellular immune responses after suprachoroidal delivery of AAV8 expressing green fluorescent protein (GFP) in rhesus macaques, and found that it can induce mild chorioretinitis that resolves after systemic corticosteroid administration, with recovery of photoreceptor morphology, but persistent immune cell infiltration after 3 months, corresponding to a loss of GFP expression from retinal pigment epithelial cells, but persistent expression in scleral fibroblasts. Suprachoroidal AAV8 triggered B cell and T cell responses against GFP, but only mild antibody responses to the viral capsid compared to intravitreal injections of the same vector and dose. Systemic biodistribution studies showed lower AAV8 levels in liver and spleen after suprachoroidal injection compared with intravitreal delivery. Our findings suggest that suprachoroidal AAV8 primarily triggers host immune responses to GFP, likely due to sustained transgene expression in scleral fibroblasts outside the blood-retinal barrier, but elicits less humoral immune reactivity to the viral capsid than intravitreal delivery due to lower egress into systemic circulation. As GFP is not native to primates and not a clinically relevant transgene, suprachoroidal AAV delivery of human transgenes may have significant translational potential for retinal gene therapy.

Drug content on receipt and over time for compounded formulations of famciclovir.

OBJECTIVES: The aim of this study was to determine famciclovir content (strength) in compounded formulations and to determine if potency changed over time. METHODS: Four concentrations of oral oil suspension in three distinct flavors, three concentrations of oral paste, three chew treats and 62.5 mg tablets from one compounding pharmacy were evaluated for famciclovir content. Specific sample preparation procedures were used for each drug formulation prior to determination of famciclovir content through mass spectrometry tandem liquid chromatography. Analysis was performed on arrival from the compounder and on days 7, 14, 28, 56 and 120. Samples were run in triplicate and concentration determined by comparison with a standard curve. Content was considered appropriate if within 90-110% of the labeled concentration. RESULTS: On arrival from the compounding pharmacy, 5/12 oral oil suspensions of varying concentrations were <90% of the labeled concentration and 3/3 oral pastes were >110%. Famciclovir content in oil suspensions ranged from 72% to 118% of the label value while oral pastes ranged from 95% to 202% of the label concentration over the 120 study days, and all concentrations varied in an unpredictable fashion. Tablets contained 90-110% of the labeled value throughout the study period. Chew treats could not be successfully analyzed. CONCLUSIONS AND RELEVANCE: This study found substantial variation in famciclovir content in the compounded products evaluated, which, in turn, raises concerns that substandard dosing could result in lack of efficacy or a failed treatment trial. Drug toxicity might also be encountered. Veterinarians must be aware that while compounded medications can improve compliance, they might not deliver the drug dose expected.

Subcutaneous administration of triamcinolone as part of the management of feline eosinophilic keratoconjunctivitis.

OBJECTIVES: The aim of this retrospective case-control study was to report the efficacy of subcutaneous triamcinolone as part of a regimen for feline eosinophilic keratoconjunctivitis (FEK). METHODS: Records and clinical photographs were reviewed and lesions semiquantitatively graded for cats with cytologically confirmed FEK. Clinical data were compared between a study population of nine cats (11 eyes) treated with, and a reference population of seven cats (eight eyes) treated without, a median of 0.11 mg/kg (range 0.10-0.20 mg/kg) of triamcinolone acetonide subcutaneously. RESULTS: Breed, sex, age and prevalence of corneal ulceration at presentation; corneal disease severity before and at the initiation of immunomodulation; and duration of antiviral treatment before immunomodulation did not differ significantly between populations (P ⩾0.059). Corneal plaques resolved in five cats each from the study and reference populations (P = 0.366). Median (range) time from immunomodulation to corneal plaque resolution did not significantly differ (P = 0.246) between the study (median 14 days; range 8-38 days) and reference (median 28 days, range 14-46 days) populations. No adverse reactions were attributed to triamcinolone administration, and all corneal ulcers in the study population re-epithelialized within 14 days (range 8-38 days) following triamcinolone injection. Time to corneal ulcer re-epithelialization following triamcinolone injection varied minimally in those receiving antivirals prior to (8 or 30 days until re-epithelialization), simultaneously with (38 days) or after (14 or 24 days) triamcinolone. CONCLUSIONS AND RELEVANCE: In otherwise healthy cats with FEK, subcutaneous administration of triamcinolone appears to be well tolerated and as efficacious as conventional topical immunomodulatory therapies. It may be especially useful in ulcerated eyes where topical immunomodulation is contraindicated.

Safety and Biocompatibility of Aflibercept-Loaded Microsphere Thermo-Responsive Hydrogel Drug Delivery System in a Nonhuman Primate Model.

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.

Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis.

Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS-441524 (5-10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]-PCR) and serial ocular imaging using Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS-441524 shows clinical efficacy and may result in clearance and long-term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.

Suprachoroidal and Subretinal Injections of AAV Using Transscleral Microneedles for Retinal Gene Delivery in Nonhuman Primates.

Retinal gene therapy using adeno-associated viruses (AAVs) is constrained by the mode of viral vector delivery. Intravitreal AAV injections are impeded by the internal limiting membrane barrier, while subretinal injections require invasive surgery and produce a limited region of therapeutic effect. In this study, we introduce a novel mode of ocular gene delivery in rhesus macaques using transscleral microneedles to inject AAV8 into the subretinal or suprachoroidal space, a potential space between the choroid and scleral wall of the eye. Using in vivo imaging, we found that suprachoroidal AAV8 produces diffuse, peripheral expression in retinal pigment epithelial (RPE) cells, but it elicited local infiltration of inflammatory cells. Transscleral subretinal injection of AAV8 using microneedles leads to focal gene expression with transduction of RPE and photoreceptors, and minimal intraocular inflammation. In comparison, intravitreal AAV8 shows minimal transduction of retinal cells, but elicits greater systemic humoral immune responses. Our study introduces a novel mode of transscleral viral delivery that can be performed without vitreoretinal surgery, with focal or diffuse transgene expression patterns suitable for different applications. The decoupling of local and systemic immune responses reveals important insights into the immunological consequences of AAV delivery to different ocular compartments surrounding the blood-retinal barrier.

Comprehensive Clinical, Diagnostic, and Advanced Imaging Characterization of the Ocular Surface in Spontaneous Aqueous Deficient Dry Eye Disease in Dogs.

PURPOSE: To perform a comprehensive clinical, diagnostic, and imaging characterization of the ocular surface in West Highland White Terriers (WHWTs) diagnosed with aqueous deficient dry eye (ADDE) disease. METHODS: Six ADDE-affected and 13 ADDE-unaffected WHWT dogs were enrolled and underwent clinical assessment and disease scoring, tear osmolarity, phenol red thread test, Schirmer tear test, tear film breakup time, fluorescein staining, Rose bengal and lissamine green vital dye staining, meibometry, corneal esthesiometry, ultrasound pachymetry, optical coherence tomography, in vivo confocal microscopy, and conjunctival biopsy. Subjective assessment of their condition was provided by owner-reported surveys. RESULTS: ADDE-affected WHWT dogs had higher median clinical disease (conjunctiva: 5.75 vs. 0.00; cornea: 14.00 vs. 5.00; total: 17.50 vs. 5.00), vital staining (Rose bengal: 2.25 vs. 1.50; lissamine green: 2.00 vs. 1.00), and histologic disease (conjunctiva: 2 vs. 0) scores when compared with the controls. In addition, ADDE-affected WHWTs had significantly lower phenol red thread test (5.0 vs. 17.5, mm/15 s), Schirmer tear test (3 vs. 20, mm/min), tear film breakup time (3.6 vs. 13.9, s) values and higher area under the curve values for meibometry (394 vs. 245, meibometry units [MU]). There were no significant differences in other tear film tests performed. Advanced imaging revealed decreased tear meniscus height (optical coherence tomography) and variable pigment deposition within corneal epithelial cells (in vivo confocal microscopy). CONCLUSIONS: This comprehensive assessment of ADDE-affected WHWTs depicts the ocular surface changes associated with quantitative lacrimal gland dysfunction. Importantly, ADDE-affected WHWTs may prove a valuable naturally occurring ADDE model for investigating underlying pathophysiological mechanisms and the development of novel therapeutics.

Medical management of deep ulcerative keratitis in cats: 13 cases.

CASE SERIES SUMMARY: Described are 13 cats diagnosed with deep ulcerative keratitis and successfully managed medically without grafting procedures. Typical treatment involved frequent topical application of serum and antibiotics (usually a fluoroquinolone and a cephalosporin). Seven cats also received systemic antibiotics. Analgesia was achieved using various combinations of topical atropine and systemic buprenorphine, robenacoxib or corticosteroids. Six cats were hospitalized for a median (range) period of 2.5 (1-8) days, typically because of frequent medication administration. Median (range) follow-up time was 41.5 (9-103) days. Median (range) number of recheck examinations was 4 (2-6). Median (range) time to corneal re-epithelialization was 21 (9-103) days. Median (range) topical antibiotic course was 29.5 (16-103) days. Median (range) duration of Elizabethan collar use was 28 (13-73) days. At the time of writing, no further recheck examinations were recommended for 10 cats; median (range) time between initial to final examinations in these cats was 35 (20-103) days. All cats retained the affected globes and were apparently comfortable and visual at the latest recheck examination. RELEVANCE AND NOVEL INFORMATION: These cases reveal that aggressive medical management is highly successful in select cats with deep ulcerative keratitis, and can result in a cosmetically acceptable, apparently comfortable and visual globe. However, therapy is intensive with frequent administration of multiple topical and sometimes systemic medications, and requires multiple veterinary visits over many weeks. Referral to a veterinary ophthalmologist for consideration of surgical stabilization is recommended, as not all cases may be amenable to the medical therapy described here.

Prophylactic and therapeutic effects of twice-daily famciclovir administration on infectious upper respiratory disease in shelter-housed cats.

OBJECTIVES: In humans with herpetic disease, early or pre-emptive famciclovir therapy reduces disease duration and severity. This prospective, masked, placebo-controlled study tested therapeutic and prophylactic effects of two famciclovir doses given to cats for 7 days following shelter entry. METHODS: Cats were assigned to prophylactic or therapeutic study arms based on clinical evidence of herpetic disease at study entry. Cats in the therapeutic arm received no treatment (n = 19), placebo (lactose; n = 18) or famciclovir at ~30 (n = 21) or ~90 mg/kg (n = 20) PO q12h for 7 days. Cats in the prophylactic arm received no treatment (n = 25) or famciclovir at ~30 (n = 28) or ~90 mg/kg (n = 27) PO q12h for 7 days. Disease scores, body weight, conjunctival feline herpesvirus 1 (FHV-1) shedding, and adoption rates were recorded on days 1 (admission), 8 (end of therapy) and 15 (1 week after cessation of therapy). RESULTS: No significant differences in clinical scores were observed among groups in the prophylactic or therapeutic arms at any of the three time points. However, within the therapeutic arm, viral shedding on day 8 was significantly higher in cats receiving no treatment than in those receiving ~30 or ~90 mg/kg famciclovir, and this effect persisted 1 week after famciclovir was stopped (day 15) only in cats receiving ~30 mg/kg, although this approached significance in cats receiving ~90 mg/kg. No significant differences in adoption rates were detected among groups in either arm throughout the study. CONCLUSIONS AND RELEVANCE: Although we did not demonstrate a statistically or clinically significant effect of famciclovir administration upon clinical signs of infectious upper respiratory disease or adoption, when it was administered at ~30 or ~90 mg/kg q12h for 1 week famciclovir reduced conjunctival FHV-1 shedding. This suggests a potential role in interrupting the infectious cycle within a shelter population; however, cost in time and resources, and stress and pathogen transmission induced by oral administration should be considered.

Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the Rhesus macaque.

Purpose: To identify changes induced by environmental tobacco smoke (ETS) in circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque and compare these changes to normal age-related changes. Tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (AMD). Methods: All Rhesus macaques were housed at the California National Primate Research Center (CNPRC), University of California, Davis. Four groups of animals were used: Group 1 (1-3 years old), Group 2 (19-28 years old), Group 3 (10-16 years old), and Group 4 (middle aged, 9-14 years old). Group 4 was exposed to smoke for 1 month. Ocular fluids and plasma samples were collected, miRNAs isolated, and expression data obtained using Affymetrix miRNA GeneTitan Array Plates 4.0. Bioinformatics analysis was done on the Affymetrix Expression Console (EC), Transcriptome Analysis Software (TAS) using ANOVA for candidate miRNA selection, followed by Ingenuity Pathway Analysis (IPA). Results: The expression of circulatory miRNAs showed statistically significant changes with age and ETS. In the plasma samples, 45 miRNAs were strongly upregulated (fold change >±1.5, p<0.05) upon ETS exposure. In the vitreous, three miRNAs were statistically significantly downregulated with ETS, and two of them (miR-6794 and miR-6790) were also statistically significantly downregulated with age. Some retinal layers exhibited a thinning trend measured with optical coherence tomography (OCT) imaging. The pathways activated were IL-17A, VEGF, and recruitment of eosinophils, Th2 lymphocytes, and macrophages. Conclusions: ETS exposure of Rhesus macaques resulted in statistically significant changes in the expression of the circulatory miRNAs, distinct from those affected by aging. The pathways activated appear to be common for ETS and AMD pathogenesis. These data will be used to develop an animal model of early dry AMD.

A Population Study of Common Ocular Abnormalities in C57BL/6N rd8 Mice.

Purpose: The purpose of this study was to quantify the frequency and severity of ocular abnormalities affecting wild-type C57BL/6N mice, the most common strain used worldwide for the creation of single-gene knockouts. Methods: A total of 2773 animals (5546 eyes) were examined at one colony at UC Davis and in three more colonies at the Institut Clinique de la Souris in Strasbourg, France. Mice were examined at 15 to 16 weeks postnatal age by performing anterior segment biomicroscopy, posterior segment examination by indirect ophthalmoscopy, intraocular pressure measurement, and optical coherence tomography of anterior and posterior segment structures. Results: Common ocular findings in the C57BL/6N strain included corneal deposits (3%), increased optical density of the anterior lens capsule (67%), punctate nuclear cataracts (98%), vitreous crystalline deposits (61%), hyaloid vascular remnant (6%), and retinal dysplasia attributed to the rd8 mutation (58%). Interestingly, retinal dysplasia was more common in male mice in all four breeding colonies evaluated in this study. The thickness of ocular tissues and compartments were measured by spectral-domain optical coherence tomography, including the central cornea, anterior chamber, vitreous, and retinal layers. Intraocular pressure was measured by rebound tonometry. Conclusions: Ocular abnormalities are common in anterior and posterior segments of the C57BL/6N mouse, the most common background on which single-gene knockout mice have been made. It is important that vision scientists understand the extent and variability of ocular findings associated with this particular genetic background of mice.

Clinical findings and outcomes for dogs with uveodermatologic syndrome.

OBJECTIVE To evaluate signalment, clinical signs, treatment, and factors affecting visual prognosis in dogs with uveodermatologic syndrome (UDS). DESIGN Retrospective case series and nested cohort study. ANIMALS 50 dogs (37 Akitas and 13 non-Akitas) with UDS evaluated at 4 ophthalmology practices. PROCEDURES Data were collected from the medical records regarding signalment, clinical signs, biopsy results, medications, adverse effects, vision and glaucoma status at initial and subsequent examinations, and duration of follow-up. Various factors were examined for associations with development of blindness or glaucoma following initial examination. RESULTS The most common ophthalmic signs included aqueous flare (n = 35 [70%]), iris abnormalities (29 [58%]), retinal detachment (23 [46%]), and choroidal depigmentation or chorioretinal infiltrates (10 [20%]). At initial examination, 36% (18/50) of dogs had glaucoma and 57% (26/46) were blind in both eyes. Twenty-five (50%) dogs had vision at their final visit, representing 78% of the 32 dogs that had vision at initial examination or regained vision during the follow-up period. In dogs that lost vision, median time to permanent blindness in both eyes was 13.5 months (range, 0.4 to 59 months) after initial examination. No significant associations with time to glaucoma or vision loss were identified for signalment variables, specific medications, or duration of clinical signs prior to initial examination. CONCLUSIONS AND CLINICAL RELEVANCE UDS commonly resulted in glaucoma, vision loss, or both in affected dogs. No evaluated factor was associated with visual prognosis; however, a subset of patients maintained vision through to the final recheck examination.

Comparison of corneal degeneration and calcific band keratopathy from 2000 to 2013 in 69 horses.

OBJECTIVE: To compare signalment, presentation, treatment, and outcome in horses diagnosed with corneal degeneration (CD) or calcific band keratopathy (CBK) at a referral hospital. ANIMALS STUDIED: Sixty-nine horses (87 eyes) diagnosed with either CD or CBK. PROCEDURES: Medical records of horses diagnosed with CD or CBK at the University of California-Davis Veterinary Medical Teaching Hospital (UCD-VMTH) between 2000 and 2013 were reviewed. Signalment, concurrent ophthalmic diagnoses, previous therapies, diagnostic tests, systemic diagnoses, treatment, follow-up, and outcomes were compared between horses diagnosed with CD or CBK. Age, breed, and gender were compared between the CD/CBK and UCD-VMTH populations. RESULTS: Thirty-three horses (42 eyes) and 36 horses (45 eyes) were diagnosed with CD and CBK, respectively. Horses with CD or CBK were significantly older (P < 0.001) than the UCD-VMTH population with a median age of 16 or 18 years, respectively. Appaloosas were significantly overrepresented in the CD/CBK population (33%) in comparison with the UCD-VMTH population (1.8%, P < 0.001). Equine recurrent uveitis was concurrently diagnosed in 67% and 84% of horses with CD or CBK, respectively. Pituitary pars intermedia dysfunction (PPID) was diagnosed significantly less often in horses with CD vs. CBK (P = 0.03). Chemical chelation with ethylenediaminetetraacetic acid was performed significantly less frequently in horses diagnosed with CD (7.1%) vs. CBK (31.1% of eyes) (P = 0.012). CONCLUSIONS: Despite some differences, equine CD and CBK are relatively similar conditions and may represent a continuum of disease severity. Horses with PPID should be monitored closely for corneal disease including CBK.

Effect of Uveal Melanocytes on Choroidal Morphology in Rhesus Macaques and Humans on Enhanced-Depth Imaging Optical Coherence Tomography.

PURPOSE: To compare cross-sectional choroidal morphology in rhesus macaque and human eyes using enhanced-depth imaging optical coherence tomography (EDI-OCT) and histologic analysis. METHODS: Enhanced-depth imaging-OCT images from 25 rhesus macaque and 30 human eyes were evaluated for choriocapillaris and choroidal-scleral junction (CSJ) visibility in the central macula based on OCT reflectivity profiles, and compared with age-matched histologic sections. Semiautomated segmentation of the choriocapillaris and CSJ was used to measure choriocapillary and choroidal thickness, respectively. Multivariate regression was performed to determine the association of age, refractive error, and race with choriocapillaris and CSJ visibility. RESULTS: Rhesus macaques exhibit a distinct hyporeflective choriocapillaris layer on EDI-OCT, while the CSJ cannot be visualized. In contrast, humans show variable reflectivities of the choriocapillaris, with a distinct CSJ seen in many subjects. Histologic sections demonstrate large, darkly pigmented melanocytes that are densely distributed in the macaque choroid, while melanocytes in humans are smaller, less pigmented, and variably distributed. Optical coherence tomography reflectivity patterns of the choroid appear to correspond to the density, size, and pigmentation of choroidal melanocytes. Mean choriocapillary thickness was similar between the two species (19.3 ± 3.4 vs. 19.8 ± 3.4 µm, P = 0.615), but choroidal thickness may be lower in macaques than in humans (191.2 ± 43.0 vs. 266.8 ± 78.0 µm, P < 0.001). Racial differences in uveal pigmentation also appear to affect the visibility of the choriocapillaris and CSJ on EDI-OCT. CONCLUSIONS: Pigmented uveal melanocytes affect choroidal morphology on EDI-OCT in rhesus macaque and human eyes. Racial differences in pigmentation may affect choriocapillaris and CSJ visibility, and may influence the accuracy of choroidal thickness measurements.

Superficial Keratectomy and Conjunctival Advancement Hood Flap (SKCAHF) for the Management of Bullous Keratopathy: Validation in Dogs With Spontaneous Disease.

PURPOSE: To evaluate the efficacy of superficial keratectomy and conjunctival advancement hood flap (SKCAHF) for the treatment of bullous keratopathy in canine patients. METHODS: Nine dogs (12 eyes) diagnosed with progressive corneal edema underwent superficial keratectomy followed by placement of conjunctival advancement hood flaps. The canine patients were examined pre- and postoperatively using in vivo confocal microscopy, ultrasonic pachymetry (USP), and Fourier-domain optical coherence tomography (FD-OCT). All owners responded to a survey regarding treatment outcomes. RESULTS: Mean central corneal thickness (CCT) as measured by FD-OCT was 1163 ± 290 µm preoperatively and significantly decreased postoperatively to 795 ± 197 µm (P = 0.001), 869 ± 190 µm (P = 0.005), and 969 ± 162 µm (P = 0.033) at median postoperative evaluations occurring at 2.2, 6.8, and 12.3 months, respectively. Owners reported significant improvement (P < 0.05) in vision and corneal cloudiness at 6.8 and 12.3 months postoperatively. The percentage of cornea covered by the conjunctival flap was correlated (P = 0.0159) with a reduction in CCT by USP at 12.3 months postoperatively. All canine patients were comfortable pre- and postoperatively. CONCLUSIONS: SKCAHF results in a reduction of corneal thickness in canine patients with bullous keratopathy. The increase in corneal thickness over time, after performing SKCAHF, is likely because of progressive endothelial decompensation. This surgery is a potentially effective intervention for progressive corneal edema in dogs that may have value in treatment of human patients with bullous keratopathy.