In vivo confocal microscopic features of canine primary corneal squamous cell carcinoma.

OBJECTIVE: To describe the in vivo confocal microscopy (IVCM) findings in dogs with primary corneal squamous cell carcinoma (SCC). ANIMALS: Eight dogs with primary corneal SCC. PROCEDURES: Dogs diagnosed with primary corneal SCC by histopathology were examined with a modified Heidelberg Retina tomograph and Rostock Cornea Module prior to surgical intervention. The findings from the IVCM examination were correlated with clinical details from ophthalmic examinations and diagnostic test results. RESULTS: Eight eyes from eight dogs with unilateral primary corneal SCC were examined. Corneal lesions were characterized with IVCM by abnormal epithelial cells that were polygonal and enlarged with marked morphological variability and anisocytosis within individual corneas. The abnormal cells displayed variable reflectivity, but most had highly reflective cellular borders and moderately reflective cytoplasm. Cells that were markedly and diffusely hyperreflective were also occasionally observed possibly representing keratinization and dyskeratosis. On IVCM, neoplastic cells were grouped into cords, clusters, and sheets, and nests of neoplastic cells often invaded the underlying corneal stroma. Keratin pearls were a frequent finding and appeared as circular whirls of neoplastic epithelial cells arranged around concentric layers of hyperreflective amorphous material within a dark cyst-like space. Abundant blood vessels and scattered leukocytes were present in all tumors. There was a high degree of morphologic agreement between IVCM analysis and histopathological findings in all cases. CONCLUSIONS: The distinguishing features of primary corneal SCC during IVCM examine were similar to those seen in histopathologic examination of tumor sections, including enlarged and pleomorphic squamous epithelial cells, anisocytosis, keratin pearl formation, and dense vascularization.

Risk factors for corneal conjunctival grafting failure in dogs at four referral centers in the southern United States (203 patients): 2015-2021.

OBJECTIVE: To report risk factors associated with conjunctival graft failure in dogs at four referral specialty centers. PROCEDURES: Records of 203 dogs (229 eyes) undergoing conjunctival graft repair of ulcerative keratitis at four hospitals from 2015 to 2021 were reviewed. Success was defined as full graft integration with globe retention at the last postoperative evaluation; vision status was reported separately. Factors assessed included patient signalment, ophthalmic examination findings, surgical factors, and follow-up information. RESULTS: Conjunctival graft failure occurred in 11% (25/229) of eyes and was significantly associated with ulcer depth, with corneal perforations having increased odds of graft failure compared with descemetoceles (odds ratio [OR] = 3.22, 95% confidence interval [CI] 1.11-9.32; p = .03) and stromal ulcers (OR = 10.89 [95% CI 1.38-86.18], p = .02). Brachycephalic dogs were significantly more likely than non-brachycephalic dogs to experience graft failure (OR = 5.02 [95% CI 1.42-17.74], p < .01). Surgery on the opposite eye relative to surgeon handedness was significantly associated with an increased risk of graft failure (OR 4.28 [95% CI 1.53-11.94], p < .01). The use of 7-0 and 8-0 suture versus 9-0 (p = .03) and the use of a combined simple continuous and interrupted pattern (p = .03) were significantly associated with an increased risk of graft failure. At the last follow-up, (median 61.5 days), 87% of dogs were visual. CONCLUSIONS: Corneal perforations, surgery on the opposite eye relative to surgeon handedness, suture size and pattern, and brachycephalic conformation were significantly associated with an increased risk of graft failure in this study. These characteristics can be considered when determining prognosis for ulcerative keratitis requiring surgical intervention.

Clinical ophthalmic parameters of the Quaker parrot (Myiopsitta monachus).

PURPOSE: Ophthalmic diagnosis in many avian species remains hindered by a lack of normative values. This study aimed to establish normal ophthalmic parameters for select diagnostic tests in clinically normal Quaker parrots. METHODS: Ninety-six captive Quaker parrots aged 8-18 years underwent ophthalmic examination to include assessment of neuro-ophthalmic reflexes, phenol red thread test, rebound tonometry, fluorescein staining, palpebral fissure length measurements, slit lamp biomicroscopy, indirect ophthalmoscopy, and ocular ultrasound biometry. RESULTS: Menace response, dazzle reflex, and direct pupillary light reflex were present for all Quaker parrots. Tear production (mean ± SD) was 13.3 ± 4.0 mm/15 s and intraocular pressure (IOP, mean ± SD) was 10.6 ± 1.4 and 6.0 ± 1.3 mmHg in the D and P rebound tonometer calibration settings, respectively. For IOP measurement, D and P calibration settings were not interchangeable, with the lesser variation of the D setting preferred in the absence of a gold standard. Ultrasound measurement of the anterior chamber depth increased with age and males had longer axial globe and vitreous lengths. Incidental adnexal and ocular lesions, identified in 36/96 (37.5%) of Quaker parrots, did not statistically affect the created reference data. CONCLUSIONS: This work provides reference values and clinical findings to assist with monitoring the health of wild populations and maintaining the health of captive Quaker parrots.

Relationship between the bacterial ocular surface microbiota and outcomes for cats with feline herpesvirus type 1 ocular surface disease.

OBJECTIVE: Feline herpesvirus 1 (FHV-1) causes ocular surface disease in domestic cats. The purpose of this study was to assess the relationship between bacterial ocular surface microbiota and outcomes for cats with FHV-1 ocular surface disease. ANIMALS STUDIED: Twenty-two shelter-housed cats with confirmed FHV-1 ocular surface disease. PROCEDURES: Animals were grouped according to FHV-1 shedding and ocular clinical scores following intervention: worsened outcome (WorOut, n = 11) or improved outcome (ImpOut, n = 11). Scoring and conjunctival sampling were completed on Days 1 and 8 of twice daily antiviral treatment. Bacterial DNA was extracted and submitted for 16S rRNA gene sequencing. Real-time polymerase chain reaction was performed for selected bacterial species. Overall DNA concentration between groups was assessed. RESULTS: Bacterial microbiota relative abundance composition was significantly different between ImpOut and WorOut groups (weighted UniFrac p = .006). Alpha diversity was significantly higher in the ImpOut group compared with the WorOut group (Shannon p = .042, Simpson's p = .022, Pielou's p = .037). Differences in the relative abundance of various phyla and species were detected between groups. Total DNA concentration was higher in the WorOut group compared with the ImpOut group (p = .04). Feline GAPDH (p = .001) and Bilophila wadsworthia (p = .024) copy number was significantly higher in the ImpOut group compared with the WorOut group. CONCLUSIONS: The results highlight the important relationship between the bacterial ocular surface microbiota and FHV-1 infection outcomes in cats treated with antiviral medications. Low bacterial species diversity, higher overall DNA (presumed predominantly bacterial) load, and certain bacterial phyla/species were associated with poor outcomes for cats with FHV-1 ocular disease.

Traumatic Injury Under COVID-19 Stay-at-Home Advisory: Experience of a New England Trauma Center.

BACKGROUND: With the onset of the COVID-19 pandemic and subsequent widespread stay-at-home advisories throughout early 2020, hospitals have noticed a decrease in illnesses unrelated to COVID-19. However, the impact on traumatic injury is relatively unknown. This study aims to characterize patterns of trauma during the COVID-19 pandemic at a Level I Trauma Center. MATERIALS & METHODS: A retrospective review was performed of adult trauma patients from March to June, in the years 2018 through 2020. Primary outcome was the number of trauma activations (volume). Secondary outcomes included activation level, mechanism of injury, mortality rate, and length of stay, and other demographic background. Trauma patterns of the 2018 and 2019 periods were combined as historical control, and compared to patterns of the biweekly-matched period of 2020. RESULTS: A total of 2,187 patients were included in analysis (Pre-COVID n = 1,572; COVID n = 615). Results were significant for decreased trauma volume but longer length of stay during COVID cohort, and for an increased proportion of males. No significant difference was found for other demographic variables, trauma mechanisms, or severity. Trauma volume patterns mirrored COVID rates in the state. CONCLUSIONS: Despite a decline in trauma volume, other trauma patterns including severity and mechanism remained unchanged during the COVID-19 period. The decreased volume was not associated with a markedly lower clinical workload, change in team structure, or provider coverage re-distribution. Our data suggests that trauma volume and severity remained high enough during COVID-19 peak to necessitate full staffing, which may provide guidance in the event of a pandemic resurgence.

An abbreviated Caprini model for VTE risk assessment in trauma.

The Caprini risk assessment model (RAM) is widely used to assess risk of venous thromboembolism (VTE). However, it is cumbersome with 31 variables and poses challenges with inter-rater reliability. This study aimed to determine if an abbreviated model could perform similarly in VTE risk assessment. We performed a retrospective review of trauma patients ≥ 18 years old and admitted for over 24 h at a Level I trauma center from January 1, 2018, to December 31, 2018. Demographic and clinical data were analyzed to generate Caprini scores. Using a p-value cutoff of < 0.05, the individual components of the original Caprini RAM most highly associated with VTE were identified and used to calculate an abbreviated Caprini score. Logistic regression assessed odds of inpatient VTE with the original or abbreviated Caprini RAMs. Receiver operating characteristic curves and c-statistics were generated to assess discriminatory ability. The study sample included 1279 patients. Ten risk factors were included in the abbreviated model (recent major surgery, length of surgery > 2 h, transfusion, restricted mobility > 72 h, central venous catheter, current major surgery, age, history of VTE, hip or leg fracture, and serious trauma). Compared to the original, the abbreviated model had a similar odds ratio (1.17 vs 1.07, both p-values < 0.001), c-statistic (0.747 vs 0.753), sensitivity (0.73 vs 0.76) and specificity (0.62 vs 0.61). An abbreviated Caprini RAM performs similarly to the original, may streamline workflow and allow for automation in electronic health records, potentially enhancing its use in resource limited settings.

Description of non-brachycephalic canine conjunctival microbiome before and after application of an antiseptic preparation.

OBJECTIVE: To evaluate canine conjunctival microbiome before and after an antiseptic preparation using aerobic culture and DNA sequencing. ANIMALS STUDIED: Six healthy non-brachycephalic dogs. PROCEDURES: Dogs randomly received povidone-iodine 1:50 dilution solution in one eye with the second eye serving as a control. Standardized volumes of solution, number of sterile cotton tipped applicators, and preparation times of 5 min were used. Aerobic culture and DNA sequencing samples were collected from inferior conjunctival fornices at baseline, immediately following, 24 h, and 4 weeks following antiseptic preparation. Aerobic culture data were evaluated using paired t-test and linear regression. Illumina platform was used to sequence bacterial DNA using primers to target the V4 region of bacterial 16S rRNA. Quantitative Insights Into Molecular Ecology (QIIME 2.0) was used to analyze data. RESULTS: Baseline aerobic cultures consisted of Bacillus (35%), Staphylococcus (30%), Streptococcus (20%), Moraxella (5%), Micrococcus (5%), and Simonsiella spp. (5%). No significant difference was detected in mean number of species cultured at baseline and following treatment (p = .465). Treatment, sample time, or interaction was not significant (p > .393). The most abundant phyla at baseline via DNA sequencing were Proteobacteria (57.04%), Actinobacteria (19.89%), Firmicutes (3.25%), and Bacteroidetes (5.5%). Alpha and beta diversity matrices at baseline and over time revealed no significant change in species richness or bacterial composition. Relative abundance of bacterial taxa did not significantly differ in treated or control eyes over time. CONCLUSIONS: Conjunctival bacterial flora identified differed between culture dependent and independent methods. The bacterial community remained stable over time after application of the antiseptic preparation.

Current ocular microbiome investigations limit reproducibility and reliability: Critical review and opportunities.

Enthusiasm for research describing microbial communities using next-generation sequencing (NGS) has outpaced efforts to standardize methodology. Without consistency in the way research is carried out in this field, the comparison of data between studies is near impossible and the utility of results remains limited. This holds true for bacterial microbiome research of the ocular surface, and other sites, in both humans and animals. In addition, the ocular surface remains under-explored when compared to other mucosal sites. Low bacterial biomass samples from the ocular surface lead to further technical challenges. Taken together, two major problems were identified: (1) Normalization of the workflow in studies utilizing NGS to investigate the ocular surface bacteriome is necessary in order to propel the field forward and improve research impact through cross-study comparisons. (2) Current microbiome profiling technology was developed for high bacterial biomass samples (such as feces or soil), posing a challenge for analyses of samples with low bacterial load such as the ocular surface. This article reviews the challenges and limitations currently facing ocular microbiome research and provides recommendations for minimum reporting standards for veterinary ophthalmologists and clinician scientists to limit inter-study variation, improve reproducibility, and ultimately render results from these studies more impactful. The move toward normalization of methodology will expedite and maximize the potential for microbiome research to translate into meaningful discovery and tangible clinical applications.

Analgesic effects of a retrobulbar block with 0.75% ropivacaine in dogs undergoing enucleation.

OBJECTIVE: To assess the analgesic effects of a retrobulbar block with ropivacaine in dogs undergoing enucleation. STUDY DESIGN: Prospective, randomized, masked placebo-controlled trial. ANIMALS: A total of 23 client-owned dogs. METHODS: Dogs were randomized to be administered a preoperative inferior-temporal palpebral retrobulbar injection of either ropivacaine 0.75% (1 mL 10 kg-1; group RG) or equivalent volume of 0.9% saline (control; group CG). Intraoperative variables recorded to detect a response to noxious stimuli included heart rate (HR) and mean arterial pressure (MAP). Three observers assessed and recorded pain using a numerical rating pain scale and visual analog scale (VAS) before anesthesia (baseline) and postoperatively at 0, 0.5, 1, 2, 3, 4, 5, 6 and 24 hours after extubation. Rescue analgesia was administered if intraoperative HR or MAP increased by ≥ 20% from the previously recorded surgical time point, average postoperative pain scores totaled ≥ 9/20, scored ≥ 3/4 in any one category with VAS ≥ 35/100, or if VAS was ≥ 35/100 with a palpation score > 0/4. RESULTS: Intraoperatively, there was no significant difference in HR or MAP between groups. Rescue analgesia was administered intraoperatively to four and one dogs and postoperatively to five and seven dogs in groups CG and RG, respectively, with no significant difference between groups. VAS scores were significantly lower in ropivacaine dogs at extubation (p = 0.02), but not at other postoperative time points. Adverse events were not observed in either group. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative retrobulbar 0.75% ropivacaine injection (1 mL 10 kg-1) provided analgesia in dogs following enucleation at extubation; however, intraoperative and postoperative pain control did not differ from a placebo injection with saline. Lack of differences between groups may have been influenced by sample size limitations.

CLINICAL OPHTHALMIC PARAMETERS OF THE TEXAS TORTOISE (GOPHERUS BERLANDIERI).

Ophthalmic studies of the Texas tortoise (Gopherus berlandieri) established normal ophthalmic parameters for select diagnostic tests in captive tortoises and assessment of differences among individuals of differing size and health status. Sixty-one tortoises of varying weight, shell size, Mycoplasma seroprevalence, and herpesvirus exposure were included. Complete ophthalmic examinations, including neuro-ophthalmic reflexes, phenol red thread test, rebound tonometry, fluorescein staining, palpebral fissure length measurement, slit lamp biomicroscopy, indirect fundoscopy, and ocular ultrasound measurements of axial globe length, anterior chamber depth, lens thickness, and vitreous length, were recorded. All tortoises had negative dazzle and pupillary light reflexes, inconsistent menace responses, and positive palpebral reflexes. Mean ± SD tear production and intraocular pressure (IOP) were 14.2 ± 5.6 mm/15 sec and 13.8 ± 2.4 mm Hg in healthy tortoises, respectively. Mycoplasma-seropositive tortoises (with or without herpesvirus exposure) had significantly increased tear production (20.2 ± 8.1 and 19.9 ± 8.9 mm/15 sec, respectively) compared with healthy seronegative tortoises (14.2 ± 5.6 mm/15 sec; P = 0.02). As body size decreased, so too did palpebral fissure length and ocular ultrasound measurements, while IOP increased. Overall, palpebral fissure length appeared relatively small, and tear production relatively increased compared with other chelonian species, likely on the basis of the relatively arid native habitat. Further work is recommended to establish baseline values in related species, as well as comparison in aquatic versus terrestrial chelonians. The authors further suggest that the finding of relatively increased tear production in tortoises may indicate the need to rule out mycoplasmosis as a cause of upper respiratory tract disease.

Uveal Malignant Melanoma in a Hybrid Macaw Parrot (Ara chloropterus × Ara militaris).

An adult male green-winged (Ara chloropterus) × military (Ara militaris) hybrid macaw of unknown age was presented to the Texas A&M Veterinary Medical Teaching Hospital for evaluation of left periocular swelling, blepharospasm, and ocular discharge. Complete ophthalmic examination and B mode ocular ultrasonography were performed to evaluate the affected eye. Ocular examination revealed a blind left globe with exophthalmos, periocular swelling, diffuse corneal edema, and severe anterior fibrinous uveitis obscuring visualization of the intraocular structures. An ultrasound examination revealed a hyperechoic mass that filled the posterior segment of the globe. Focal discontinuity of the posterior sclera suggested scleral rupture. Enucleation with histopathology was recommended and performed 1.5 months later. Intraoperatively, a heavily pigmented and friable soft tissue mass extruded through the posterior sclera and extended into the orbit. Histologically, the mass was consistent with a malignant melanoma. The patient died 18 hours after the surgical procedure because of unknown complications. Postmortem examination did not identify evidence of metastasis. This study described the clinical appearance and histopathologic findings of a rare ocular neoplasm with extrascleral extension in a hybrid macaw. Although uncommon in psittacine birds, primary ocular melanocytic neoplasms may display features of malignancy with scleral or orbital invasion, or both.

Normative ocular data for juvenile and adult Japanese quail (Coturnix japonica).

OBJECTIVE: To obtain normative ocular data for Japanese quail as they mature from juveniles to adults. ANIMALS STUDIED: Twenty-six captive Japanese quail comprising thirteen males and thirteen females, free of ocular disease, were included in the study. PROCEDURES: Ophthalmic reference values were measured in both eyes at 1 and 5 months of age. A complete ophthalmic examination was performed, including neuro-ophthalmic reflexes, slit lamp biomicroscopy, phenol red thread test (PRTT), rebound tonometry, fluorescein staining, horizontal corneal diameter measurement, indirect ophthalmoscopy, and ocular ultrasound biometry. Ultrasound biomicroscopy measurements of axial globe length, lens thickness, vitreal chamber length, and pecten length were recorded. The depth of the anterior chamber was calculated by subtracting the lens thickness and vitreous length from the axial globe length. Measures of association and descriptive statistics were analyzed using STATA-14 and STATA-15. RESULTS: Juvenile and adult females were heavier than age-matched males. Weight, intraocular pressure, horizontal corneal diameter, axial globe length, and lens thickness measurements increased with age. No statistically significant differences were found in the remainder of measurements among individuals in different sex or age-groups. CONCLUSIONS: This work provides reference values and clinical findings that can be used in future research on quail and ocular disease.

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.

Self-limiting Orbital Emphysema Following Ocular Evisceration and Demonstration of Nasolacrimal-Oropharyngeal Communication in a South African Ostrich (Struthio camelus australis).

A 25-year-old, male, sanctuary-owned, South African ostrich (Struthio camelus australis) was evaluated for orbital emphysema after evisceration of a nonvisual and chronically irritated eye. On initial ophthalmic examination, the ostrich's left eye displayed severe corneal fibrosis, broad anterior synechia, and a shallow anterior chamber, all suggestive of a previous corneal perforation. Conjunctival hyperemia and eyelid crusts were also present, reportedly associated with chronic rubbing. Evisceration of the left eye was performed by excising the eyelid margins, conjunctiva, nictitans, cornea, and intraocular contents. Four weeks postoperatively, a nonpainful, fluctuant swelling of the surgical site was noted. Trocarization of the surgical site verified orbital emphysema and served to temporarily decompress the orbit. Orbital emphysema reoccurred within 48 hours but gradually regressed without intervention over the subsequent 9 months. A Jones test was performed in the healthy, right eye and demonstrated clear communication to the oropharynx. To our knowledge, this is the first reported case of an evisceration performed on an ostrich and the first reported case of orbital emphysema in any avian species. It is probable that the emphysema noted in this case was secondary to nasolacrimal duct-oropharynx communication.

Next Generation of Global Surgeons: Aligning Interest With Early Access to Global Surgery Education.

BACKGROUND: Although interest in global surgery is increasing among medical students,1 several questions remain unanswered such as: the association of demographics with said interest, the extent that global surgical burden education has been integrated into medical education, and the availability of global surgery electives. This study aimed to assess the current state of global surgery education in the United States (U.S.) to support recommendations for future curriculum development. MATERIALS AND METHODS: An anonymous online survey was distributed to medical students currently enrolled in the U.S. Descriptive data were compiled regarding interest in and access to global surgery programs; demographic data were analyzed using chi-squared testing for categorical variables. RESULTS: A total of 754 students from 18 medical schools throughout the U.S. responded to the survey. Only complete responses were included in final analysis (n = 658). Most of the respondents (66%) reported interest in global surgery, with a higher proportion of those interested being in their preclinical years. However, the majority (79%) reported that global surgery issues are rarely or never addressed in their required curriculum. Over half of respondents were unaware of whether their school even offers such programs. CONCLUSIONS: Although interest in global surgery is on the rise among medical students, results suggest that many currently lack exposure to global surgery concepts in their medical education. To that end, early exposure may be most effective during the preclinical years, so that the next generation may align global surgery participation with clinical aspirations, with the ultimate goal of addressing global disparities.

Canine ocular and periocular snakebites requiring enucleation: A report of 19 cases.

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.

Overlap of abnormal photoreceptor development and progressive degeneration in Leber congenital amaurosis caused by NPHP5 mutation.

Ciliary defects can result in severe disorders called ciliopathies. Mutations in NPHP5 cause a ciliopathy characterized by severe childhood onset retinal blindness, Leber congenital amaurosis (LCA), and renal disease. Using the canine NPHP5-LCA model we compared human and canine retinal phenotypes, and examined the early stages of photoreceptor development and degeneration, the kinetics of photoreceptor loss, the progression of degeneration and the expression profiles of selected genes. NPHP5-mutant dogs recapitulate the human phenotype of very early loss of rods, and relative retention of the central retinal cone photoreceptors that lack function. In mutant dogs, rod and cone photoreceptors have a sensory cilium, but develop and function abnormally and then rapidly degenerate; L/M cones are more severely affected than S-cones. The lack of outer segments in mutant cones indicates a ciliary dysfunction. Genes expressed in mutant rod or both rod and cone photoreceptors show significant downregulation, while those expressed only in cones are unchanged. Many genes in cell-death and -survival pathways also are downregulated. The canine disease is a non-syndromic LCA-ciliopathy, with normal renal structures and no CNS abnormalities. Our results identify the critical time points in the pathogenesis of the photoreceptor disease, and bring us closer to defining a potential time window for testing novel therapies for translation to patients.

Tropical Keratopathy (Florida Spots) in Cats.

The authors used microscopy and synchrotron-based small-angle X-ray scattering analysis (SAXS) to describe lesions macroscopically typical of tropical keratopathy ("Florida spots") from 6 cats on St Kitts. Microscopically, there were varying degrees of epithelial hyperplasia and thinning of the cornea (by 4% to 18%) due to loss of corneal stroma associated with dense accumulations of collagen in the superficial stroma. The collagen fibrils in lesions were wider and had more variable diameters (39.5 ± 5.0 nm, mean ± SD) than in normal corneas (25.9 ± 3.6 nm; P < .01). There were occasional vacuoles (<1 µm) in the corneal epithelial basement membrane but no evidence of inflammation, edema, stromal neovascularization, fibrosis, acid-fast organisms, or structures suggestive of a fungal organism. SAXS analysis showed collagen fibril diameters and variation in size were greater in stroma containing the lesions compared to normal corneas (48.8 ± 4.5 nm vs 35.5 ± 2.6; P < .05). The d-spacing of collagen in the stroma of lesions and normal corneas was the same, but the average orientation index of collagen in lesions was greater (0.428 ± 0.08 vs 0.285 ± 0.03; P < .05). A survey revealed Florida spots lesions were static over time and became less obvious in only 1 of 6 affected cats adopted on St Kitts and taken to areas in the US where lesions are not reported. An anterior stromal collagen disorder with various degrees of epithelial hyperplasia is the pathologic hallmark of lesions clinically identical to Florida spots in cats from St Kitts.

An unusual case of feline acute corneal hydrops: atypical disease presentation and possible in vivo detection of Descemet's membrane detachment in the cat's unaffected eye.

A 1-year-old, female spayed, domestic shorthair cat presented for blepharospasm of the right eye. Slit-lamp biomicroscopic examination showed focal corneal ulceration and presumptive keratomalacia of the right eye. Examination of the left eye was normal apart from a focal endothelial opacity. Within the first 24 h of medical management, the right eye developed marked corneal edema and globular anterior protrusion of the corneal surface consistent with feline acute corneal hydrops (FACH). Surgical management consisted of a bridge conjunctival graft, nictitating membrane flap, and temporary tarsorrhaphy. Resolution of corneal edema and pain occurred in the right eye within 24 days. Spectral domain optical coherence tomography (SD-OCT) of the anterior segment was performed in both eyes. Conjunctival tissue from the bridge graft precluded examination of deeper corneal structures in the right eye. The left eye displayed a focal separation of the corneal endothelium and Descemet's membrane from the overlying stroma. These SD-OCT findings are similar to the analogous syndrome found in humans and represent a potential etiology for FACH of the right eye in the case presented here. Unfortunately, the cat was lost to follow-up and the progression of this lesion to FACH in the left eye could not be determined.

Homocitrate synthase connects amino acid metabolism to chromatin functions through Esa1 and DNA damage.

The enzyme homocitrate synthase (HCS) catalyzes the first step in lysine biosynthesis, and early biochemical data placed it in the cytoplasm or mitochondria, where most amino acid synthesis occurs. It was therefore surprising when refined fractionation techniques and specific immunoreagents clearly demonstrated its localization to the nucleus. These observations raised the question of whether HCS had a function within the nucleus independent of lysine synthesis. We demonstrate that HCS encoded by LYS20 in yeast is linked to the key process of DNA damage repair through the essential MYST family histone acetyltransferase Esa1 and the H2A.Z histone variant. This discovery indicates that HCS has a role in addition to amino acid synthesis, and that it functions in nuclear activities involving chromatin regulation that are distinct from its previously established role in lysine biosynthesis. The chromatin-linked roles are dependent on nuclear localization of Lys20, but are independent of HCS catalytic activity. Thus, Lys20 appears to have evolved as a bifunctional protein that connects cellular metabolism with chromatin functions.