Topical netarsudil for the treatment of primary corneal endothelial degeneration in dogs.

This study evaluated the tolerability and efficacy of the topical rho-kinase inhibitor netarsudil for canine primary corneal endothelial degeneration (PCED). Twenty-six eyes of 21 client-owned dogs with PCED were enrolled in a prospective, randomized, vehicle control clinical trial and received topical netarsudil 0.02% (Rhopressa®) or vehicle control twice daily (BID) for the first 4 months. Then, all patients received netarsudil for the next 4 or 8 months. Complete ophthalmic examination, ultrasonic pachymetry, Fourier-domain optical coherence tomography, and in vivo confocal microscopy were performed at baseline and 1, 2, 4, 6, 8 and 12 months. Effect of netarsudil on central corneal thickness (CCT), percentage of cornea with edema, and endothelial cell density (ECD) were evaluated by repeated measures ANOVA. Kaplan-Meier curves and log-rank test were used to compare corneal edema and clinical progression of eyes in netarsudil versus vehicle control groups. All dogs developed conjunctival hyperemia in at least one eye while receiving netarsudil. Unilateral transient reticulated intraepithelial bullae and stromal hemorrhage were observed respectively in 2 dogs in the netarsudil group. Two dogs showed persistently decreased tear production while receiving netarsudil, requiring topical immunomodulatory treatment. No significant differences in CCT, ECD, corneal edema or clinical progression were observed between netarsudil or vehicle treated eyes. When comparing efficacy of topical netarsudil BID and topical ripasudil 0.4% administered four times daily from our previous study, dogs receiving ripasudil had significantly less progression than those receiving netarsudil.

Choroidal Changes in Rhesus Macaques in Aging and Age-Related Drusen.

Purpose: Choroidal vascular changes occur with normal aging and age-related macular degeneration (AMD). Here, we evaluate choroidal thickness and vascularity in aged rhesus macaques to better understand the choroid's role in this nonhuman primate model of AMD. Methods: We analyzed optical coherence tomography (OCT) images of 244 eyes from 122 rhesus macaques (aged 4-32 years) to measure choroidal thickness (CT) and choroidal vascularity index (CVI). Drusen number, size, and volume were measured by semiautomated annotation and segmentation of OCT images. We performed regression analyses to determine any association of CT or CVI with age, sex, and axial length and to determine if the presence and volume of soft drusen impacted these choroidal parameters. Results: In rhesus macaques, subfoveal CT decreased with age at 3.2 µm/y (R2 = 0.481, P < 0.001), while CVI decreased at 0.66% per year (R2 = 0.257, P < 0.001). Eyes with soft drusen exhibited thicker choroid (179.9 ± 17.5 µm vs. 162.0 ± 27.9 µm, P < 0.001) and higher CVI (0.612 ± 0.051 vs. 0.577 ± 0.093, P = 0.005) than age-matched control animals. Neither CT or CVI appeared to be associated with drusen number, size, or volume in this cohort. However, some drusen in macaques were associated with underlying choroidal vessel enlargement resembling pachydrusen in human patients with AMD. Conclusions: Changes in the choroidal vasculature in rhesus macaques resemble choroidal changes in human aging, but eyes with drusen exhibit choroidal thickening, increased vascularity, and phenotypic characteristics of pachydrusen observed in some patients with AMD.

Effects of alfaxalone on induction quality of inhalation anesthesia in domestic pigeons (Columba livia domestica).

Several studies have documented the effects of anesthesia on pigeons. However, previous studies using pigeons have not examined a combination of injection and inhalation anesthesia. This study aimed to evaluate the effects of intramuscular (IM) administration of alfaxalone in conjunction with mask induction on the quality of isoflurane anesthesia in healthy domestic pigeons (Columba livia domestica). In a randomized, double-blind, crossover study consisting of two phases, six healthy adult pigeons were anesthetized twice with a washout period of 7 days. In each phase, the pigeons were randomly assigned IM administration of either alfaxalone (4 mg/kg) or an equal volume of normal saline. After 20 min, anesthesia was induced with isoflurane through a face mask. Once voluntary movement of the limbs and eyelids ceased, the face mask was removed, and the trachea was intubated. The quality of anesthesia was assessed by scoring sedation prior to anesthetic induction, induction, and recovery. Heart rate, respiratory rate, cloacal temperature, and noninvasive systolic, diastolic, and mean arterial pressure were recorded before the IM injection (baseline) and during the procedure. The minimum anesthetic concentration of isoflurane was determined using the "bracketing" method. Moderate sedation (sedation scores of 2 and 3) was observed only with alfaxalone administration. In the alfaxalone group, the induction score was significantly higher (better induction quality) than in the control group (P=0.041). The combination of alfaxalone and mask induction was effective for inhalation anesthesia in pigeons.

Mice Deficient in TAZ (Wwtr1) Demonstrate Clinical Features of Late-Onset Fuchs' Endothelial Corneal Dystrophy.

Purpose: We sought to define the role of Wwtr1 in murine ocular structure and function and determine the role of mechanotransduction in Fuchs' endothelial corneal dystrophy (FECD), with emphasis on interactions between corneal endothelial cells (CEnCs) and Descemet's membrane (DM). Methods: A Wwtr1 deficient mouse colony was established, and advanced ocular imaging, atomic force microscope (AFM), and histology/immunofluorescence were performed. Corneal endothelial wound healing was assessed using cryoinjury and phototherapeutic keratectomy in Wwtr1 deficient mice. Expression of WWTR1/TAZ was determined in the corneal endothelium from normal and FECD-affected patients; WWTR1 was screened for coding sequence variants in this FECD cohort. Results: Mice deficient in Wwtr1 had reduced CEnC density, abnormal CEnC morphology, softer DM, and thinner corneas versus wildtype controls by 2 months of age. Additionally, CEnCs had altered expression and localization of Na/K-ATPase and ZO-1. Further, Wwtr1 deficient mice had impaired CEnC wound healing. The WWTR1 transcript was highly expressed in healthy human CEnCs comparable to other genes implicated in FECD pathogenesis. Although WWTR1 mRNA expression was comparable between healthy and FECD-affected patients, WWTR1/TAZ protein concentrations were higher and localized to the nucleus surrounding guttae. No genetic associations were found in WWTR1 and FECD in a patient cohort compared to controls. Conclusions: There are common phenotypic abnormalities seen between Wwtr1 deficient and FECD-affected patients, suggesting that Wwtr1 deficient mice could function as a murine model of late-onset FECD. Despite the lack of a genetic association between FECD and WWTR1, aberrant WWTR1/TAZ protein subcellular localization and degradation may play critical roles in the pathogenesis of FECD.

A Spontaneous Nonhuman Primate Model of Myopic Foveoschisis.

Purpose: Foveoschisis involves the pathologic splitting of retinal layers at the fovea, which may occur congenitally in X-linked retinoschisis (XLRS) or as an acquired complication of myopia. XLRS is attributed to functional loss of the retinal adhesion protein retinoschisin 1 (RS1), but the pathophysiology of myopic foveoschisis is unclear due to the lack of animal models. Here, we characterized a novel nonhuman primate model of myopic foveoschisis through clinical examination and multimodal imaging followed by morphologic, cellular, and transcriptional profiling of retinal tissues and genetic analysis. Methods: We identified a rhesus macaque with behavioral and anatomic features of myopic foveoschisis, and monitored disease progression over 14 months by fundus photography, fluorescein angiography, and optical coherence tomography (OCT). After necropsy, we evaluated anatomic and cellular changes by immunohistochemistry and transcriptomic changes using single-nuclei RNA-sequencing (snRNA-seq). Finally, we performed Sanger and whole exome sequencing with focus on the RS1 gene. Results: Affected eyes demonstrated posterior hyaloid traction and progressive splitting of the outer plexiform layer on OCT. Immunohistochemistry showed increased GFAP expression in Müller glia and loss of ramified Iba-1+ microglia, suggesting macro- and microglial activation with minimal photoreceptor alterations. SnRNA-seq revealed gene expression changes predominantly in cones and retinal ganglion cells involving chromatin modification, suggestive of cellular stress at the fovea. No defects in the RS1 gene or its expression were detected. Conclusions: This nonhuman primate model of foveoschisis reveals insights into how acquired myopic traction leads to phenotypically similar morphologic and cellular changes as congenital XLRS without alterations in RS1.

Ocular morphologic traits in the American Cocker Spaniel may confer primary angle closure glaucoma susceptibility.

Acute primary angle closure glaucoma is a potentially blinding ophthalmic emergency requiring prompt treatment to lower the elevated intraocular pressure in humans and dogs. The PACG in most of canine breeds is epidemiologically similar to humans with older and female patients overrepresented with the condition. The American Cocker Spaniel (ACS) is among the most common breeds observed with PACG development in dogs. This study initially sought to identify genetic risk factors to explain the high prevalence of PACG in ACSs by using a case-control breed-matched genome-wide association study. However, the GWAS failed to identify candidate loci associated with PACG in this breed. This study then assessed intrinsic ocular morphologic traits that may relate to PACG susceptibility in this breed. Normal ACSs without glaucoma have a crowded anterior ocular segment and narrow iridocorneal angle and ciliary cleft, which is consistent with anatomical risk factors identified in humans. The ACSs showed unique features consisting of posterior bowing of iris and longer iridolenticular contact, which mirrors reverse pupillary block and pigment dispersion syndrome in humans. The ACS could hold potential to serve as an animal model of naturally occurring PACG in humans.

A genome-wide association study to investigate genetic loci associated with primary glaucoma in American Cocker Spaniels.

OBJECTIVE: To identify genetic associations with primary glaucoma (PG) in American Cocker Spaniels using a genome-wide association study (GWAS). ANIMALS: A nationwide ambidirectional case-control cohort study was performed in American Cocker Spaniels that had an ophthalmic examination performed by a veterinarian. Ninety-four dogs with PG (cases) and 111 dogs without glaucoma (controls) met phenotypic criteria and had a blood sample collected after receiving informed owner consent. PROCEDURES: Genomic DNA was extracted from whole blood samples and genotyped (CanineHD BeadChip, Illumina Inc). A case-control GWAS using a linear mixed model was performed, and 3 significance thresholds were calculated (1) using a Bonferroni correction on all single nucleotide polymorphisms (SNPs) included in the GWAS, (2) using a Bonferroni correction on only the unlinked SNPs from a pruned data set, and (3) using 10,000 random phenotype permutations. RESULTS: Following genotype data quality control, 89 cases and 93 controls were included in the GWAS. We identified an association on canine chromosome (CFA10); however, it did not reach statistical significance. Potential candidate genes within the surrounding linkage disequilibrium interval include coiled-coil domain containing 85A (CCDC85A) and extracellular growth factor containing fibulin extracellular matrix protein 1 (EFEMP1). CLINICAL RELEVANCE: Primary glaucoma in the American Cocker Spaniel is a complex heterogeneous disease that may be influenced by a locus on CFA10. The candidate genes CCDC85A and EFEMP1 within the identified linkage disequilibrium interval have been shown to be involved in human open-angle glaucoma.

Normal Corneal Thickness and Endothelial Cell Density in Rhesus Macaques (Macaca mulatta).

Purpose: To define the normal range of central corneal thickness (CCT) and corneal endothelial cell density (ECD) in rhesus macaques (Macaca mulatta) and the effects of age, body weight, sex, and intraocular pressure (IOP) on these parameters. Methods: Ophthalmic examinations were performed on 144 rhesus macaques without anterior segment pathology. The CCT was measured via ultrasound pachymetry (USP) and specular microscopy, and the ECD was semiautomatically and manually counted using specular microscopy. Rebound tonometry was used to measure IOP. Linear regression and mixed-effects linear regression models were used to evaluate the effects of age, body weight, sex, and IOP on CCT and ECD. Results: We included 98 females and 46 males with an age range of 0.2 to 29.4 years. The mean CCT by USP and specular microscopy were 483 ± 39 and 463 ± 33 µm, respectively, and were statistically different (P < 0.001). The ECDs were 2717 ± 423 and 2747 ± 438 cells/mm2 by semiautomated and manual analysis, respectively. Corneal endothelial degeneration was identified in one aged rhesus macaque. Conclusions: The mean USP and specular microscopy CCT values differed significantly, whereas the semiautomatic and manual ECD did not. The CCT was associated with the IOP and sex, whereas the ECD was associated with body weight and age (P < 0.05). As in humans, corneal disease in rhesus macaques is uncommon. Translational Relevance: Establishing reference values is fundamental to use rhesus macaques as a model for corneal disease or to identify toxicity in studies of ocular drugs or devices.

Topical Ripasudil for the Treatment of Primary Corneal Endothelial Degeneration in Dogs.

Purpose: The purpose of this study was to evaluate the tolerability and efficacy of topical rho-kinase inhibitor ripasudil in the treatment of primary corneal endothelial degeneration (PCED) in dogs. Methods: Twenty-one eyes of 12 client-owned, PCED-affected dogs received topical ripasudil 4 times daily. Ophthalmic examination, ultrasonic pachymetry (USP), Fourier-domain optical coherence tomography (FD-OCT), and in vivo confocal microscopy were performed at baseline and 1, 3, 6, and 12 months. Effects of treatment on corneal thickness, corneal edema extent, and endothelial cell density (ECD) were evaluated by repeated-measures ANOVA or Friedman test. Individual eyes were classified as improved, progressed, or stable at 12 months using clinical response criteria. Kaplan-Meier curves and log-rank test were used to compare ripasudil-treated eyes to age-, breed/size-, and disease stage-matched historical controls. Results: During treatment, 12 dogs developed conjunctival hyperemia, 4 demonstrated reticular bullous epithelial edema, and 2 developed corneal stromal hemorrhage. No adverse event necessitated permanent cessation of ripasudil. Central corneal thickness measured by USP significantly progressed from baseline to 12 months. Corneal thickness by FD-OCT, ECD, and edema extent did not differ over time. Considered individually, 5 eyes improved, 8 remained stable, and 8 progressed. The log-rank test found less edema progression in ripasudil-treated eyes compared to historical controls. Conclusions: Ripasudil was well-tolerated in PCED-affected dogs. Response to therapy varied; 62% of eyes showed improved or stable disease whereas 38% progressed. Ripasudil-treated eyes progressed more slowly than historical controls. Translational Relevance: Topical ripasudil offered a therapeutic benefit in a subset of patients using a canine model of endothelial degeneration, which may guide future trials in humans.

Multimodal ocular imaging of known and novel corneal stromal disorders in dogs.

BACKGROUND: Imaging features obtained with Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM) for corneal stromal disorders have been sparsely reported in dogs. This case report is a compilation of imaging features for three cases of different stromal disorders of the canine cornea which have not yet been reported elsewhere. CASE PRESENTATION: Lipid deposition in case 1 appeared as needle-shaped hyperreflective lines along the collagen lamellae, which correlated histologically with lipid clefts. In case 2, glycosaminoglycan accumulation by mucopolysaccharidosis type 1 caused diffuse stromal hyperreflectivity and depletion of keratocytes on IVCM and was associated with secondary corneal degeneration presumed to be calcium deposition. In case 3, posterior corneal stromal opacities in the absence of ocular inflammation were identified. Hyperreflective particles were scattered in the middle and posterior corneal stroma on FD-OCT. With IVCM, hyperreflective deposits were identified within keratocytes and the number of enlarged keratocytes containing hyperreflective deposits increased towards the posterior stroma. The bilateral, non-inflammatory nature and unique appearance with IVCM is most consistent with a posterior stromal dystrophy reminiscent of pre-Descemet corneal dystrophy described in humans. CONCLUSIONS: In vivo multimodal corneal imaging facilitated instantaneous microstructural analysis and may be valuable in the differential diagnosis of corneal stromal disorders in veterinary clinical practice. The non-specific nature of imaging findings occurs in some conditions such as mucopolysaccharidosis, thus in vivo corneal imaging should be complemented with other gold standard methods of definitive diagnosis.

Canine endotheliitis: Clinical characteristics, advanced imaging features, and treatment.

OBJECTIVE: To describe the clinical findings, multimodal corneal imaging features and treatment in canine patients diagnosed with endotheliitis. ANIMALS STUDIED: Four canine patients met inclusion criteria for bilateral corneal disease with endothelial inflammation and secondary corneal edema that responded to topical anti-inflammatory treatment. METHODS: The patients selected underwent a complete ophthalmic examination with emphasis on the cornea including ultrasound pachymetry (USP), Fourier-domain optical coherence tomography (FD-OCT), in vivo confocal microscopy (IVCM), and digital slit lamp photography. RESULTS: All patients in this study demonstrated thickened corneas due to edema with USP and FD-OCT. With IVCM, mild to severe polymegathism and pleomorphism of corneal endothelial cells, reduced endothelial cell density, hyperreflective keratic precipitates (KPs), and extracellular debris as well as hyporeflective pseudoguttata were observed. With FD-OCT, hyperreflective KPs were commonly observed on the inferior cornea. Clinical examination and advanced imaging results were consistent with a diagnosis of endotheliitis. All patients initially responded to topical anti-inflammatory treatment and required continued therapy; two patients also received topical netarsudil, a rho-associated coiled-coil kinase inhibitor. CONCLUSION: Endotheliitis should be considered for canine patients with bilateral edema that is most severe in the inferior cornea. Careful inspection of Descemet's membrane-endothelial complex should be performed for KPs or inflammatory debris. Chronic administration of topical anti-inflammatories may be necessary to prevent flare-ups of endotheliitis.

Age-related changes in the rhesus macaque eye.

PURPOSE: To assess age-related changes in the rhesus macaque eye and evaluate them to corresponding human age-related eye disease. METHODS: Data from eye exams and imaging tests including intraocular pressure (IOP), lens thickness, axial length, and retinal optical coherence tomography (OCT) images were evaluated from 142 individuals and statistically analyzed for age-related changes. Quantitative autofluorescence (qAF) was measured as was the presence of macular lesions as related to age. RESULTS: Ages of the 142 rhesus macaques ranged from 0.7 to 29 years (mean = 16.4 years, stdev = 7.5 years). Anterior segment measurements such as IOP, lens thickness, and axial length were acquired. Advanced retinal imaging in the form of optical coherence tomography and qAF were obtained. Quantitative assessments were made and variations by age groups were analyzed to compare with established age-related changes in human eyes. Quantitative analysis of data revealed age-related increase in intraocular pressure (0.165 mm Hg per increase in year of age), ocular biometry (lens thickness 7.2 µm per increase in year of age; and axial length 52.8 µm per increase in year of age), and presence of macular lesions. Age-related changes in thicknesses of retinal layers on OCT were observed and quantified, showing decreased thickness of the retinal ganglion cell layer and inner nuclear layer, and increased thickness of photoreceptor outer segment and choroidal layers. Age was correlated with increased qAF by 1.021 autofluorescence units per increase in year of age. CONCLUSIONS: The rhesus macaque has age-related ocular changes similar to humans. IOP increases with age while retinal ganglion cell layer thickness decreases. Macular lesions develop in some aged animals. Our findings support the concept that rhesus macaques may be useful for the study of important age-related diseases such as glaucoma, macular diseases, and cone disorders, and for development of therapies for these diseases.

Animal models of corneal endothelial dysfunction to facilitate development of novel therapies.

Progressive corneal endothelial disease eventually leads to corneal edema and vision loss due to the limited regenerative capacity of the corneal endothelium in vivo and is a major indication for corneal transplantation. Despite the relatively high success rate of corneal transplantation, there remains a pressing global clinical need to identify improved therapeutic strategies to address this debilitating condition. To evaluate the safety and efficacy of novel therapeutics, there is a growing demand for pre-clinical animal models of corneal endothelial dysfunction. In this review, experimentally induced, spontaneously occurring and genetically modified animal models of corneal endothelial dysfunction are described to assist researchers in making informed decisions regarding the selection of the most appropriate animal models to meet their research goals.

Advanced Retinal Imaging and Ocular Parameters of the Rhesus Macaque Eye.

Purpose: To determine the range of normal ocular biometry and perform advanced retinal imaging and functional assessment of the rhesus macaque eye. Methods: We performed ocular phenotyping on rhesus macaques at the California National Primate Research Center. This process consisted of anterior and posterior segment eye examination by ophthalmologists, advanced retinal imaging, and functional retinal electrophysiology. Results: Full eye examinations were performed on 142 animals, consisting of pupillary light reflex, tonometry, external examination and photography, anterior slit lamp examination, and posterior segment examination by indirect ophthalmoscopy. Ages of the rhesus macaques ranged from 0.7 to 29 years (mean, 16.4 ± 7.5 years). Anterior segment measurements such as intraocular pressure (n = 142), corneal thickness (n = 84), lens thickness (n = 114), and axial length (n = 114) were acquired. Advanced retinal imaging in the form of fundus photography (n = 78), optical coherence tomography (n = 60), and quantitative autofluorescence (n = 44) was obtained. Electroretinography (n = 75) was used to assay retinal function. Quantitative analyses of the macular structure, retinal layer segmentation, and rod and cone photoreceptor electrical responses are reported. Quantitative assessments were made and variations between sexes were analyzed to compare with established sex changes in human eyes. Conclusions: The rhesus macaque has an ocular structure and function very similar to that of the human eye. In particular macular structure and retinal function is very similar to humans, making this species particularly useful for the study of macular biology and development of therapies for cone photoreceptor disorders. Translational Relevance: Rhesus macaques are an ideal model for future vision science studies of human eye diseases.

Pharmacological inhibition of Kv3 on oxidative stress-induced cataract progression.

Oxidative stress is one of the most important risk factors for cataractogenesis. Previous studies have indicated that BDS-II, a Kv3 channel blocker, plays pivotal roles in oxidative stress-related diseases. This study demonstrates that BDS-II exerts a protective effect on cataractogenesis. Specifically, BDS-II was observed to inhibit lens opacity induced by H2O2. BDS-II was also determined to inhibit cataract progression in a sodium selenite-induced in vivo cataract model by inhibiting reduction of the total GSH. In addition, BDS-II was demonstrated to protect human lens epithelial cells against H2O2-induced cell death. Our results suggest that BDS-II is a potential pharmacological candidate in cataract therapy.

Quantitative Fundus Autofluorescence in Rhesus Macaques in Aging and Age-Related Drusen.

Purpose: To employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD). Methods: The qAF imaging was performed on eyes of 26 rhesus macaques (mean age 18.8 ± 8.2 years, range 4-27 years) with normal-appearing fundus or with age-related soft drusen using a confocal scanning laser ophthalmoscope with 488 nm excitation and an internal fluorescence reference. Eyes with soft drusen also underwent spectral-domain optical coherence tomography imaging to measure drusen volume and height of individual drusen lesions. The qAF levels were measured from the perifoveal annular ring (quantitative autofluorescence 8 [qAF8]) using the Delori grid, as well as focally over individual drusen lesions in this region. The association between qAF levels and age, sex, and drusen presence and volume were determined using multivariable regression analysis. Results: Mean qAF levels increased with age (P < 0.001) and were higher in females (P = 0.047). Eyes with soft drusen exhibited reduced mean qAF compared with age-matched normal eyes (P = 0.003), with greater drusen volume showing a trend toward decreased qAF levels. However, qAF levels are focally increased over most individual drusen (P < 0.001), with larger drusen appearing more hyperautofluorescent (R2 = 0.391, P < 0.001). Conclusions: In rhesus macaques, qAF levels are increased with age and female sex, but decreased in eyes with soft drusen, similar to human AMD. However, drusen lesions appear hyperautofluorescent unlike those in humans, suggesting similarities and differences in RPE lipofuscin between humans and NHPs that may provide insight into drusen biogenesis and AMD pathogenesis.

Effect of Three Different Sedatives on Electroretinography Recordings in Domestic Pigeons (Columba livia).

This study was conducted to compare the effects of 3 different sedative agents on electroretinography (ERG) in domestic pigeons (Columba livia). Six pigeons were sedated with alfaxalone, xylazine, and medetomidine at separate times with a 1-week washout period between sedative administration. After sedation with each agent, pigeons underwent the modified ERG protocol adapted from the standardized protocol for dogs. The scotopic mixed rod and cone response was recorded after 20 minutes of dark adaptation, and the photopic cone response and photopic flicker response were recorded after 10 minutes of light adaptation. Either a 1-way analysis of variance or a Kruskall-Wallis test was used to compare the a-wave and b-wave implicit time and amplitude. No significant differences were observed in the scotopic mixed rod and cone response among all 3 sedatives used. Compared with alfaxalone, medetomidine significantly prolonged the a-wave implicit time, depressed the b-wave amplitude of photopic cone response, and prolonged the peak implicit time of the photopic flicker response (P < .05). These results show that medetomidine has a depressant effect on photopic ERG in pigeons at a dosage that produces light sedation.

Intraocular Pressure Measurement by Rebound Tonometry (TonoVet) in Normal Pigeons (Columba livia).

We evaluated the applicability of a rebound tonometer (TonoVet) in pigeon eyes and established normal reference intraocular pressure (IOP) values in healthy pigeons; 20 eyes of euthanized pigeons were used for calibration of the TonoVet and 48 eyes of 24 adult pigeons were used for measurement of reference IOP. First, IOP of pigeon eyes ex vivo were measured using the 'd' and the 'p' modes of the TonoVet and compared to manometric IOP values from 5 to 80 mm Hg. Then, to establish normal reference values, IOP was measured from clinically normal pigeons in vivo. The 'd' and the 'p' modes of the TonoVet showed a strong linear correlation with the manometric IOP (R2 = .996 and .991, respectively). The obtained regression formulas were: y1 = 0.439x + 2.059 and y2 = 0.330x - 0.673, respectively (y1, 'd' mode of TonoVet; y2, 'p' mode of TonoVet; x, manometric IOP). The 'd' and the 'p' modes consistently measured one-half and one-third of the actual IOP, respectively. Therefore, the formula obtained through the 'd' mode was applied to obtain reference values. The calibrated IOP of normal pigeon eyes was 19.5 ± 4.4 mm Hg. The actual IOP could be calculated using the presented formula. Considering the limitations of the 'p' mode, use of the 'd' mode is more appropriate. Therefore, the TonoVet rebound tonometry under the 'd' mode is a reliable method for measuring IOP in pigeons.

Effects of prostaglandin-mediated and cholinergic-mediated miosis on morphology of the ciliary cleft region in dogs.

OBJECTIVE To compare morphology of the ciliary cleft (CC) region in dogs after topical administration of latanoprost, pilocarpine, or a combination of latanoprost and pilocarpine. ANIMALS 6 Beagles. PROCEDURES A prospective 4-phase crossover study with washout periods was performed. Latanoprost (phase L), pilocarpine (phase P), pilocarpine followed by latanoprost (phase PL), and latanoprost followed by pilocarpine (phase LP) were administered to the right eye. Artificial tears were administered to the left eye (control eye). For each phase, pupil diameter and intraocular pressure (IOP) were measured and ultrasonographic biomicroscopy was performed 2 hours after topical treatment. Angle opening distance (AOD), ciliary cleft width (CCW), ciliary cleft length (CCL), and ciliary cleft area (CCA) were evaluated. RESULTS All treated eyes had marked miosis without significant differences in pupil diameter among phases. Significant IOP reductions were detected for all phases, except phase P. The AOD and CCA were significantly increased in all phases for treated eyes, compared with results for control eyes. The CCW was significantly increased in phases P, PL, and LP; CCL was significantly increased in phases PL and LP. Comparison of treated eyes among phases revealed that CCW differed significantly between phases L and P and between phases L and PL. CONCLUSIONS AND CLINICAL RELEVANCE Prostaglandin-mediated and cholinergic-mediated miosis caused variations in CC configurations. When latanoprost and pilocarpine were used in combination, the first drug administered determined the cleft morphology, which was not fully reversed by the second drug. The CC morphology did not fully explain IOP reductions.

Comparison of corneal thickness measurements using ultrasound pachymetry, ultrasound biomicroscopy, and digital caliper in frozen canine corneas.

OBJECTIVE: To evaluate the clinical efficacy among ultrasound pachymetry (UP), ultrasound biomicroscopy (UBM), and manual measurement (MM) with digital caliper by comparing corneal thickness (COT) values obtained from frozen canine corneas ex vivo. PROCEDURES: COT was measured using UP, UBM, and MM in eight enucleated normal canine eyes frozen at -20 °C for 4 weeks. After thawing at room temperature for 2 h, the COT values were obtained from five sites on each cornea: central corneal thickness (CCOT), thickness at the 3, 6, 9, and 12 o'clock positions (3COT, 6COT, 9COT, and 12COT, respectively). For each device, measurements were performed three times at each designated site by one operator. Intraclass correlation coefficient, repeated-measures analysis of variance, and Bland-Altman plot were performed for statistical analyses. RESULTS: The mean CCOT was 839.0 ± 138.2, 857.6 ± 127.9, and 849.1 ± 132.8 µm for UP, UBM, and MM, respectively. There was no statistically significant difference among the measurements by all three devices (P > 0.05). The statistical agreement among these devices was also shown to be good according to Bland-Altman plots. In addition, the values measured on the peripheral sites of the cornea (3COT, 6COT, 9COT, and 12COT) also revealed no significant differences among the three devices. The difference between CCOT and peripheral corneal thickness was also statistically insignificant. CONCLUSIONS: The UP, UBM, and MM measurements showed statistically similar COT values. The UBM and UP provided accurate and reliable measurements comparable to MM and could be used effectively for clinical COT measurements.