Measurement of plasma gentamicin concentrations postchemical ciliary body ablation in dogs with chronic glaucoma.

OBJECTIVE: To investigate the absorption of gentamicin into the plasma after an intravitreal injection in dogs and to report the success rate of this procedure in lowering the intraocular pressure. ANIMALS: Twenty-four client-owned dogs with chronic, end-stage glaucoma. PROCEDURES: Dogs received a unilateral (22) or bilateral (2) intravitreal injection of 25-40 mg of gentamicin (mean ± SD dose 2.57 ± 1.65 mg/kg and range 0.61-7.50 mg/kg) and 1 mg of dexamethasone per eye. Blood samples were collected at various time points following the intravitreal injection. Plasma concentrations of gentamicin were determined by liquid chromatography and mass spectrometry. RESULTS: The total plasma concentration of gentamicin ranged from 0.21 to 9.71 µg/mL (mean ± SD 2.15 ± 2.03). The mean gentamicin CMAX was 2.29 µg/mL at 2.54 h with a terminal half-life of 9.8 h. The success rate of the chemical ablation procedure was 86.4% (19/22 eyes) in dogs that had at least 1 month of follow-up. CONCLUSIONS: Intravitreal injection of gentamicin in eyes with chronic glaucoma resulted in detectable plasma levels in dogs and was successful in lowering the intraocular pressure in 86.4% of the eyes after the first procedure.

Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment.

Cyclic nucleotide-gated (CNG) ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM). ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD) simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ) domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients.

Effects of oral administration of anti-inflammatory medications on inhibition of paracentesis-induced blood-aqueous barrier breakdown in clinically normal cats.

OBJECTIVE: To assess inhibitory effects of orally administered anti-inflammatory medications on paracentesis-induced intraocular inflammation in clinically normal cats. ANIMALS: 30 clinically normal domestic shorthair cats. PROCEDURES: Cats were randomly assigned to a control group and 4 treatment groups. Cats in the treatment groups received an anti-inflammatory medication orally once daily at 7 AM (acetylsalicylic acid [40.5 mg/cat], meloxicam [0.1 mg/kg], prednisone [5 mg/cat], or prednisolone [5 mg/cat]) for 5 days beginning 2 days before paracentesis-induced breakdown of the blood-aqueous barrier (BAB) and continuing until 2 days after paracentesis. Paracentesis of the anterior chamber was performed in 1 randomly selected eye of each cat. Fluorophotometry was performed in both eyes of each cat immediately before (time 0) and 6, 24, and 48 hours after paracentesis. RESULTS: At 24 and 48 hours after paracentesis, fluorescein concentration in the eye subjected to paracentesis in the cats receiving prednisolone was decreased, compared with that in the control cats. At 48 hours, a decrease in the fluorescein concentration was also apparent in the eye subjected to paracentesis in the cats receiving meloxicam, compared with that in the control cats. There was no evidence of treatment effects for acetylsalicylic acid or prednisone. There was no evidence of treatment effects in eyes not subjected to paracentesis. CONCLUSIONS AND CLINICAL RELEVANCE: Orally administered prednisolone and meloxicam significantly decreased intraocular inflammation in clinically normal cats with paracentesis-induced BAB breakdown. Oral administration of prednisolone or meloxicam may be an effective treatment for cats with uveitis.

Effects of ocular administration of ophthalmic 2% dorzolamide hydrochloride solution on aqueous humor flow rate and intraocular pressure in clinically normal cats.

OBJECTIVE: To determine the effects of ocular administration of ophthalmic 2% dorzolamide hydrochloride solution on aqueous humor flow rate (AHFR) and intraocular pressure (IOP) in clinically normal cats. ANIMALS: 20 clinically normal domestic shorthair cats. PROCEDURES: Following an acclimation period, IOP was measured in each eye of all cats 5 times daily for 3 days to determine baseline values. Fifteen cats received 1 drop of 2% dorzolamide solution and 5 cats received 1 drop of control solution in each eye every 8 hours for 5 days (treatment phase). The IOP of each eye was measured 5 times during each day of the treatment phase. Prior to and after the treatment phase, AHFR in both eyes of each cat was measured via fluorophotometry. RESULTS: Prior to treatment, AHFR or IOP did not differ between the treatment and control groups. In dorzolamide-treated cats, mean AHFR after the treatment phase (3.47 ± 1.5 µL/min) was significantly lower than the value prior to treatment (5.90 ± 2.2 µL/min) and mean IOP during the treatment phase (11.1 ± 1.0 mm Hg) was significantly lower than the baseline mean IOP (14.9 ± 1.0 mm Hg). In the control group, IOP values did not differ before or during the treatment phase and AHFRs did not differ before and after the treatment phase. CONCLUSIONS AND CLINICAL RELEVANCE: Ocular administration of 2% dorzolamide solution significantly decreased AHFR and IOP in clinically normal cats. Application of 2% dorzolamide solution may be an effective treatment in cats with glaucoma.

Evaluation of the aqueous humor flow rate in the eyes of clinically normal cats by use of fluorophotometry.

OBJECTIVE: To evaluate aqueous humor flow rate in the eyes of clinically normal cats by use of a noninvasive technique successfully used in other species. ANIMALS: 20 domestic shorthair cats. PROCEDURES: 1 drop of 10% fluorescein sodium was instilled into both eyes of 5 cats every 5 minutes until 3 drops had been administered. Fluorophotometry was performed at 2, 4, 5, 6, 7, 8, 9, and 10 hours after fluorescein application to monitor fluorescein removal and determine aqueous humor flow rate. The 3-drop protocol was used for the remaining 15 cats, and fluorophotometry was performed at 5, 6, 7, and 8 hours after fluorescein application. Aqueous humor flow rates were calculated manually by use of established equations with minor adjustments to constant values to reflect feline anatomic features. Correlation coefficients and slope ratios were calculated to assess the legitimacy of the flow rate data. Paired t tests were calculated to assess for differences between the right and left eyes. RESULTS: Mean ± SD calculated aqueous humor flow rate in the right, left, and both eyes of the 20 cats was 5.94 ± 2.30 µL/min, 5.05 ± 2.06 µL/min, and 5.51 ± 2.21 µL/min, respectively. Correlation coefficients and slope ratios revealed that the aqueous humor flow rates were accurate. No significant differences in values for the right and left eyes were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Accurate aqueous humor flow values for cats can be determined by use of the fluorophotometric technique evaluated in this study.

Ophthalmomyiasis externa in a puppy due to Cuterebra infestation.

An 8 wk old Scottish terrier was evaluated for a 2×2 cm mass located directly adjacent to the lateral canthus of the right eye. Examination revealed a well-developed Cuterebra larva at the lateral aspect of the orbital cavity, anchored at the lateral canthus. The larva was manually removed under general anesthesia, and the eyelid margin was repaired. Systemic and topical antibiotics along with systemic anti-inflammatory treatment were instituted. The lesion healed completely, revealing a normal functional right eye 10 days after removal of the Cuterebra larva. Careful manual removal of the larva is recommended along with correction of any resultant conformational defects. The remaining cavity can be left to heal; however, antibiotic therapy is recommended.

Ocular parameters in a captive colony of fruit bats.

OBJECTIVES: To establish normal reference ranges of ocular parameters including phenol read thread, palpebral fissure length, horizontal and vertical corneal diameter, upright and hanging intraocular pressure (IOP) and to report ophthalmic examination findings of the anterior segment and lens, in a population of captive fruit bats. ANIMALS STUDIED: Eyes of 30 bats of three species were included in this study: 10 (5 males, 5 females) Malayan Flying Foxes (Pteropus vampyrus), 10 (5 males, 5 females) Little Golden-mantled Flying Foxes (Pteropus pumilus), and 10 (4 males, 6 females) Island Flying Foxes (Pteropus hypomelanus). RESULTS: The most common ophthalmic examination findings included iris-iris persistent pupillary membranes (83%), nuclear sclerosis (56.7%), prominent arterial circle (40%), iridal hyperpigmented foci (30%), pupillary margin cysts (27%), and third eyelid defects (20%). The mean, among all species for: phenol red thread was 20.23 ± 1.28 mm/15 s both eyes (OU); palpebral fissure length was 13.34 ± 0.33 mm for OU; for horizontal corneal diameter was 10.72 ± 0.32 mm for OU; for vertical corneal diameter was 9.90 ± 0.30 mm for OU; for the hanging intraocular pressures was 19.38 ± 0.77 mmHg for OU; for upright IOP was 13.95 ± 0.60 mmHg for OU. Measurements for the individual species groups and eyes were also calculated. CONCLUSIONS: Results revealed the IOP of bats in a hanging position were significantly higher than the IOP of bats in an upright position. The size of the bat, between the species, affected palpebral fissure length, horizontal corneal diameter, and vertical corneal diameter. Information about the ocular structures and normal ophthalmic parameters for the Pteropus species is crucial for species protection because of dependence on vision for survival.

Relationship of the iridocorneal angle, as measured using ultrasound biomicroscopy, with post-operative increases in intraocular pressure post-phacoemulsification in dogs.

OBJECTIVE: To investigate the relationship of the iridocorneal angle as it appears on ultrasound biomicroscopy (UBM) to increases in IOP post-phacoemulsification in the canine eye. Animals studied 47 eyes of 28 dogs of various age, sex, and breed. METHODS: The ciliary process and limbus were used as a reference points to measure the angle opening distance (AOD), which was set by multiplying 0.45 by the distance between the ciliary process and limbus (when measured from the ciliary process). Pressure measurements were taken at five set points: Before, immediately post-, one day post-, 1 week post-, and 1 month post-phacoemulsification. RESULTS: A weak relationship between the AOD and the IOP one day post-phacoemulsification (Intercept: 2.83, Slope: -1.24, P-value: 0.0155) was observed. No relationship immediately post-operative (Intercept: 3.45, Slope: -1.34, P-value: 0.0651), 1 week post-phacoemulsification (Intercept: 2.31, Slope: -0.01, P-value: 0.9829), 1 month post-phacoemulsification (Intercept: 1.85, Slope: -0.49, P-value: 0.1533) was observed. The pre-operative measurements made with UBM were: Distance from limbus to ciliary process (DLCP): (Minimum: 1.152, Maximum: 2.992, Mean: 1.91, SD: 0.468); AOD (Minimum: 0.104, Maximum: 0.764, Mean: 0.40, SD: 0.172). CONCLUSIONS: The relationship between AOD as measured by UBM pre-operatively is weakly associated with IOP pressure elevations at day one post-phacoemulsification. Further study is required prospectively to establish the importance of this relationship. Initial measurements of the canine iridocorneal angle were created, suggesting a method to be used in the future to establish true canine normal measurements.