Effect of intracameral epinephrine on heart rate, post-operative ocular hypertension, and long-term outcome following canine phacoemulsification.

PURPOSE: To determine the effect of intrsacameral epinephrine on heart rate, blood pressure, post-operative ocular hypertension, and complications following canine phacoemulsification. PROCEDURES: A prospective, double-blinded, controlled trial was carried out using 30 client-owned dogs undergoing phacoemulsification. Eyes were randomly assigned to a treatment group receiving intracameral (IC) epinephrine (n = 31) or balanced salt solution (n = 25) at the beginning of surgery. Heart rate, post-operative intraocular pressures, and outcomes were compared between treatment groups. RESULTS: No adverse reactions to IC epinephrine or saline were observed. Post-operative ocular hypertension developed at the 2 and/or 4 hours pressure reading in 35% and 46% in the epinephrine and saline groups, respectively (P = .5072). There were 9.7% and 23.1% eyes that developed complications in the IC epinephrine and saline groups, respectively (P = .2373). CONCLUSIONS: Intracameral epinephrine is safe to use, and non-significant decreases in post-operative ocular hypertension and long-term complications were observed.

Evaluation of retinal morphology of canine sudden acquired retinal degeneration syndrome using optical coherence tomography and fluorescein angiography.

PURPOSE: To describe the optical coherence tomography (OCT) and fluorescein angiography changes in dogs with sudden acquired retinal degeneration syndrome (SARDS). METHODS: Retinal OCT was performed on 10 SARDS dogs and eight control dogs. Tomograms were collected in four quadrants around the optic nerve. Measurements were collected from the photoreceptor layer, the outer nuclear layer, the outer retina, the inner retina and the whole retina thickness in all quadrants. Sodium fluorescein was injected intravenously and serial fundic photographs were collected for a 5 minute period post-injection. RESULTS: In all quadrants, the outer nuclear layer (dorsal temporal P = 0.0000, dorsal nasal P = 0.0001, ventral temporal P = 0.0002, ventral nasal P = 0.000) and outer retina (dorsal temporal P = 0.0001, dorsal nasal P = 0.0002, ventral temporal P = 0.0054, ventral nasal P = 0.0084) measurements were significantly decreased in SARDS dogs. The whole retina thickness was significantly decreased in the dorsal temporal (P = 0.0082) and ventral temporal (P = 0.0428) retina. There were no significant differences in the photoreceptor layer thickness or inner retinal thickness between SARDS and control dogs. All SARDS dogs had a loss of definition of all of the photoreceptor bands on OCT. Two SARDS dogs had multifocal small retinal detachments and one of these dogs exhibited fluorescein leaking at the detachment sites. CONCLUSIONS: The significant reduction in the outer nuclear layer and the loss of band signals in the photoreceptor layers in dogs with SARDS identified on OCT support the previous histopathology findings. Small detachments may occasionally be detected on OCT and they may leak fluorescein.

Chromatic Pupillometry as a Putative Screening Tool for Heritable Retinal Disease in Rhesus Macaques.

Purpose: Non-human primates (NHPs) are useful models for human retinal disease. Chromatic pupillometry has been proposed as a noninvasive method of identifying inherited retinal diseases (IRDs) in humans; however, standard protocols employ time-consuming dark adaptation. We utilized shortened and standard dark-adaptation protocols to compare pupillary light reflex characteristics following chromatic stimulation in rhesus macaques with achromatopsia to wild-type (WT) controls with normal retinal function. Methods: Nine rhesus macaques homozygous for the p.R656Q mutation (PDE6C HOMs) and nine WT controls were evaluated using chromatic pupillometry following 1-minute versus standard 20-minute dark adaptations. The following outcomes were measured and compared between groups: pupil constriction latency, peak constriction, pupil constriction time, and constriction velocity. Results: Pupil constriction latency was significantly longer in PDE6C HOMs with red-light (P = 0.0002) and blue-light (P = 0.04) stimulation versus WT controls. Peak constriction was significantly less in PDE6C HOMs with all light stimulation compared to WT controls (P < 0.0001). Pupil constriction time was significantly shorter in PDE6C HOMs versus WT controls with red-light (P = 0.04) and white-light (P = 0.003) stimulation. Pupil constriction velocity was significantly slower in PDE6C HOMs versus WT controls with red-light (P < 0.0001), blue-light (P < 0.0001), and white-light (P = 0.0002) stimulation. Dark adaptation time only significantly affected peak (P = 0.008) and time of pupil constriction (P = 0.02) following blue-light stimulation. Conclusions: Chromatic pupillometry following 1- and 20-minute dark adaptation is an effective tool for screening NHPs for achromatopsia. Translational Relevance: Rapid identification of NHPs with IRDs will provide animal research models to advance research and treatment of achromatopia in humans.

Retinal degeneration in mice and humans with neuronal ceroid lipofuscinosis type 8.

BACKGROUND: Ceroid lipofuscinosis type 8 belongs to a heterogenous group of vision and life-threatening neurodegenerative diseases, neuronal ceroid lipofuscinosis (NCL). Effective therapy is limited to a single drug for treatment of ceroid lipofuscinosis type 2, necessitating animal disease models to facilitate further therapeutic development. Murine models are advantageous for therapeutic development due to easy genetic manipulation and rapid breeding, however appropriate genetic models need to be identified and characterized before being used for therapy testing. To date, murine models of ocular disease associated with ceroid lipofuscinosis type 8 have only been characterized in motor neuron degeneration mice. METHODS: Cln8-/- mice were produced by CRISPR/Cas9 genome editing through the International Mouse Phenotyping Consortium. Ophthalmic examination, optical coherence tomography, electroretinography, and ocular histology was performed on Cln8-/- mice and controls at 16 weeks of age. Quantification of all retinal layers, retinal pigmented epithelium, and the choriocapillaris was performed using images acquired with ocular coherence tomography and planimetry of histologic sections. Necropsy was performed to investigate concurrent systemic abnormalities. Clinical correlation with human patients with CLN8-associated retinopathy is provided. RESULTS: Retinal degeneration characterized by retinal pigment epithelium mottling, scattered drusen, and retinal vascular attenuation was noted in all Cln8-/- mice. Loss of inner and outer photoreceptor segment demarcation was noted on optical coherence tomography, with significant thinning of the whole retina (P=1e-9), outer nuclear layer (P=1e-9), and combined photoreceptor segments (P=1e-9). A global reduction in scotopic and photopic electroretinographic waveforms was noted in all Cln8-/- mice. Slight thickening of the inner plexiform layer (P=0.02) and inner nuclear layer (P=0.004), with significant thinning of the whole retina (P=0.03), outer nuclear layer (P=0.01), and outer photoreceptor segments (P=0.001) was appreciated on histologic sections. Scattered lipid vacuoles were noted in splenic red pulp of all Cln8-/- mice, though no gross systemic abnormalities were detected on necropsy. Retinal findings are consistent with those seen in patients with ceroid lipofuscinosis type 8. CONCLUSIONS: This study provides detailed clinical characterization of retinopathy in adult Cln8-/- mice. Findings suggest that Cln8-/- mice may provide a useful murine model for development of novel therapeutics needed for treating ocular disease in patients with ceroid lipofuscinosis type 8.