SCH 412499: biodistribution and safety of an adenovirus containing P21(WAF-1/CIP-1) following subconjunctival injection in Cynomolgus monkeys.

Monkey studies were conducted for the preclinical safety assessment of SCH 412499, an adenovirus encoding p21, administered by subconjunctival injection prior to trabeculectomy for postoperative maintenance of the surgical opening. Biodistribution of SCH 412499 was minimal and there was no systemic toxicity. Findings included swollen, partially closed or shut eye(s) and transient congestion in the conjunctiva. A mononuclear cell infiltrate was present in the conjunctiva, choroid and other ocular tissues, but completely or partially resolved over time. Electroretinograms and visual evoked potentials revealed no adverse findings. Thus, the findings are not expected to preclude the clinical investigation of SCH 412499.

Efficacy of two chondroitin sulfate ophthalmic solutions in the therapy of spontaneous chronic corneal epithelial defects and ulcerative keratitis associated with bullous keratopathy in dogs.

OBJECTIVE: To determine the efficacy of two antimicrobial-chondroitin sulfate ophthalmic solutions in the therapy of spontaneous chronic corneal epithelial defects (SCCED) and ulcerative keratitis associated with bullous keratopathy in dogs. ANIMALS STUDIED: Eighty dogs with SCCED and 14 dogs with ulcerative keratitis associated with bullous keratopathy. PROCEDURE: Following manual debridement of nonadherent epithelium, dogs were treated topically with a chondroitin sulfate ophthalmic solution containing either tobramycin or ciprofloxacin. Patients were re-evaluated at 2-week intervals for 4 weeks. RESULTS: After 2 weeks of treatment, 53.6% of eyes with SCCED and 17.6% of eyes with ulcerative keratitis associated with bullous keratopathy had healed. After 4 weeks of treatment, 81.0% of eyes with SCCED and 23.5% of eyes with ulcerative keratitis associated with bullous keratopathy had healed. There were no statistically significant differences in healing percentages between the tobramycin-chondroitin sulfate solution treatment groups and the ciprofloxacin-chondroitin sulfate solution treatment groups. Two dogs with SCCED, one treated with the tobramycin-chondroitin sulfate solution and the other treated with the ciprofloxacin-chondroitin sulfate solution, developed sterile corneal stromal abscesses during the study. CONCLUSIONS: Topical therapy with an antimicrobial-chondroitin sulfate ophthalmic solution combined with manual debridement of nonadherent epithelium compares favorably with other published medical and surgical therapies for SCCED; however, these compounds are only equivocally more effective than therapy with manual debridement alone. These solutions appear to be ineffective in the treatment of ulcerative keratitis associated with bullous keratopathy. The significance of the two cases of corneal stromal abscessation is unknown at this time and warrants further investigation.

Veterinary ophthalmology in laboratory animal studies.

In this overview the current status of the role of veterinary ophthalmology in laboratory animal studies is discussed. Attention is devoted to current regulatory requirements and study construction, examination techniques commonly used in studies, and a consideration of species characteristics that may be important to investigators. Methods for recording data are discussed with examples of recording systems.

Spontaneous cataracts in laboratory rabbits.

OBJECTIVE: To document the occurrence and incidence of spontaneously occurring cataracts in older New Zealand White (NZW) and New Zealand White x New Zealand Red (NZW x NZR - F1) rabbits during prescreening examinations at Alcon Laboratories. PROCEDURES: A retrospective study was conducted on prescreening examination records of NZW and NZW x NZR (F1) rabbits at Alcon Laboratories between April 1999 and May 2001. RESULTS: A total of 946 rabbits (670 NZW and 276 NZW x NZR) ranging in age from 77 to 288 days were examined. Of the NZW rabbits, 333 were males and 337 were females. Of the NZW x NZR (F1) rabbits, 139 were males and 137 were females. Thirty-eight NZW rabbits (23 males and 15 females) exhibited immature cataracts in one or both eyes, and three NZW x NZR (F1) rabbits (one male and two females) exhibited cataracts in one or both eyes. The overall incidence of cataracts was 4.3% of all rabbits. Males and females were equally affected, but a significant difference in the incidence of cataracts existed between the NZW and NZW x NZR (F1) rabbits with 5.7% of the NZW rabbits affected and 1.1% of the NZW x NZR (F1) rabbits affected. CONCLUSION: Spontaneous juvenile cataracts occur in rabbits and may develop as incidental lesions during toxicologic studies. The incidence of cataracts noted in our studies is consistent with an autosomal recessive mode of inheritance, but further studies are needed to confirm the mode or modes of inheritance. Hybrid pigmented rabbits (F1 or NZW x NZR) exhibited a significantly lower incidence of cataracts.

Bilateral neuroepithelial choristomas of the optic disc in a cynomolgus monkey (Macaca fascicularis): a case report.

A 6-year-old intact male cynomolgus monkey of Chinese origin was received at the Sierra Biomedical Facility. While physical examination revealed good body condition with no abnormalities, routine ophthalmic examination revealed bilateral proliferative optic neuropathy involving the dorsal aspect of the optic disc. No changes were noted in the appearance of the lesions over 8 months, and fluoroescein angiography revealed no abnormalities other than obstruction of the view of the retinal vessels by the lesions. Histopathologic studies revealed characteristics consistent with a diagnosis of bilateral neuroepithelial choristoma.