Effects of perioperative topical dorzolamide hydrochloride-timolol maleate administration on incidence and severity of postoperative ocular hypertension in dogs undergoing cataract extraction by phacoemulsification.

OBJECTIVE To assess the effects of topically applied 2% dorzolamide hydrochloride-0.5% timolol maleate ophthalmic solution (DHTM) on incidence and severity of postoperative ocular hypertension (POH; ie, intraocular pressure [IOP] > 25 mm Hg) in dogs undergoing cataract extraction by phacoemulsification. DESIGN Randomized, masked, controlled study. ANIMALS 103 dogs (180 eyes). PROCEDURES Pertinent history, signalment, and ophthalmic examination findings were recorded. Dogs received 1 drop of DHTM or sham treatment solution (sterile, buffered, isotonic eye drops) in both eyes 14 hours and 2 hours before anesthetic induction and at the time of corneal incision closure (ie, end of surgery); IOPs were assessed by rebound tonometry 2, 4, 6, and 8 hours after surgery and between 7:30 and 8:00 am on the following day. Dogs with IOPs of 26 to 45 mm Hg received 1 drop of 0.005% latanoprost solution topically; the surgeon's treatment of choice was used for dogs with IOPs > 45 mm Hg. Incidence of POH and postoperative IOPs were compared between treatment groups. RESULTS DHTM treatment resulted in significantly lower incidence of POH than did sham treatment at the level of the dog (18/53 [34%] vs 31/50 [62%]) and the eye (24/94 [26%] vs 42/86 [48%]). Mean IOP did not differ between groups at the time of POH detection. The DHTM-treated eyes that developed POH were significantly more likely to have a 1-hour follow-up IOP < 25 mm Hg after latanoprost administration than were sham-treated eyes (19/25 [76%] vs 18/35 [51%]; OR, 3.87). CONCLUSIONS AND CLINICAL RELEVANCE Multidose perioperative administration of DHTM in dogs undergoing phacoemulsification reduced the incidence of POH and improved responsiveness of POH to latanoprost treatment.

Cyclosporine A prevents ex vivo PCO formation through induction of autophagy-mediated cell death.

The purpose of this study was to determine the Cyclosporine A (CsA) dose and minimum drug delivery time needed to prevent posterior capsule opacification (PCO) in an ex vivo canine model and evaluate the mechanism of CsA-induced cell death. Canine lens epithelial cells (LEC) were treated with CsA and changes in cell migration, proliferation, and density were monitored over time. CsA-treated LEC underwent transmission electron microscopy (TEM), immunofluorescence, and immunoblotting in the presence or absence of autophagy inhibitors to evaluate the mechanism of cell death. Lens capsules were harvested from canine cadaver eyes for an ex vivo model of PCO. Lens capsules were treated with CsA for 1, 2, 3, 4, 5, 6, or 7 days, and subsequently maintained in culture for a total of 28 days in the absence of drug. CsA reduced LEC viability in a dose dependent manner. Morphologically, CsA-treated LEC were swollen, had intact nuclei, lacked peripheral chromatin condensation, and demonstrated prominent vacuolization; TEM revealed autophagosomes. LC3-II protein expression and acridine orange fluorescence increased in CsA-treated cells. A small non-significant induction of cleaved caspase-3 was observed in CsA-treated LEC. Lens capsules treated with 5, 6, or 7 days of 10 µg/mL CsA showed a significant decrease in ex vivo PCO formation; 6 days of drug delivery prevented PCO. This study finds that morphologic changes, formation of acidic vesicles, and increased expression of LC3-II supports the hypothesis that CsA mediates LEC death via autophagy; this is a novel finding in the lens. Induction of CsA-induced apoptosis was minimal. Six days of intracapsular CsA drug delivery prevented ex vivo PCO formation.

The effect of topical ocular corticosteroid administration in dogs with experimentally induced latent canine herpesvirus-1 infection.

Recurrent herpes simplex virus-1 (HSV-1) ocular infection is a frequent cause of morbidity and blindness. Factors that trigger viral reactivation are poorly understood and the role of topical ocular corticosteroid administration in the development of recurrent HSV-1 ocular disease is not clear. Clinical reports and epidemiological studies suggested topical corticosteroids may reactivate latent HSV-1 and result in recrudescent ocular disease; however, experimental studies to establish this causal relationship produced inconsistent results. The previous experimental studies were performed by infecting unnatural host species with HSV-1 and aspects of viral behavior and reactivation within these animals may differ from the host for which the virus is adapted. The purpose of the study reported here was to determine if topical ocular corticosteroid administration results in viral reactivation and recrudescent ocular disease in a host-adapted pathogen animal model of HSV-1 recurrent ocular disease. Canine herpesvirus-1 (CHV-1) is a corticosteroid-sensitive alphaherpesvirus that is biologically related to HSV-1 and induces similar ocular lesions in canids during recurrent infection. A randomized, masked, placebo-controlled, crossover study was performed. Primary ocular CHV-1 infection was experimentally induced in mature specific pathogen-free beagles by topical ocular inoculation and the presence of reactivatable latency was later confirmed by administration of an immunosuppressive dosage of systemic corticosteroid to the dogs. Twelve months following experimental CHV-1 reactivation, dogs were administered either topical ocular prednisolone acetate (1.0% ophthalmic suspension, one drop in both eyes, four times daily) or placebo (artificial tear solution, one drop in both eyes, four times daily) for 28 days. After a 14 day washout period, the treatment groups were reversed and study agents administered for an additional 28 days. Ophthalmic examinations, in vivo ocular confocal microscopy, real-time quantitative CHV-1 polymerase chain reaction assays, and CHV-1 serum neutralization antibody titers were performed at regular intervals throughout the study. Viral reactivation was not detected in dogs administered topical ocular prednisolone or placebo as determined by clinical ocular disease recrudescence, in vivo ocular confocal microscopic findings, ocular viral shedding, and serologic response. Similar to other animal models of recurrent HSV-1 ocular infection, the behavior of latent CHV-1 in dogs may differ from HSV-1 in humans; however, results of the present study suggest administration of topical ocular prednisolone at the evaluated drug concentration, dosing frequency, and treatment duration is not likely to result in detectable reactivation of latent CHV-1 in experimentally infected dogs. This may be attributed to insufficient systemic absorption of locally administered corticosteroid to reactivate latent virus and produce recurrent disease. Crystalline corneal opacities that were apparently not associated with viral reactivation were detected by clinical examination and in vivo confocal microscopy in two dogs during topical ocular prednisolone administration. The crystalline keratopathy may have resulted from corneal degeneration associated with metaherpetic disease, corticosteroid administration, or a combination of both factors.