Intravitreal toxicity of high-dose etanercept.

PURPOSE: The aim of this study was to evaluate the retinal toxicity of high-dose intravitreal etanercept, a U.S. Food and Drug Administration-approved anti-inflammatory drug, in the rabbit model. METHODS: Twenty (20) New Zealand albino rabbits were divided into 5 groups (n=4); eyes in each group were intravitreally injected with one of the following doses of etanercept: 125 microg, 250 microg, 500 microg, 1 mg, or 2.5 mg. One (1) eye in each animal was used for the study dose; the fellow eye was injected with buffered sterile saline as a control. All animals were examined using indirect ophthalmoscopy and slit-lamp biomicroscopy before and after intravitreal injection and at days 1, 7, and 14. Electroretinography (ERG) was performed on all animals before intravitreal injection and 14 days after injection. The animals were euthanized on day 14. Histological preparations of the enucleated eyes were examined with light microscopy for retinal toxicity. RESULTS: Clinical examination, histological evaluation, and ERG results of all 5 groups demonstrated no signs of retinal toxicity. CONCLUSIONS: Intravitreal doses as high as 2.5 mg of etanercept did not cause retinal toxicity. Intravitreal doses of up to 2.5 mg of etanercept may provide a more potent, prolonged effect than the lower doses previously recommended.

Intravitreal toxicity of garenoxacin.

PURPOSE: To assess the retinal toxicity of varying concentrations of intravitreally injected garenoxacin. METHODS: Twenty eyes of 20 New Zealand albino rabbits were used for this study. The animals were anesthetized with ketamine (35-50 mg/kg) and xylazine (3-5 mg/kg). Garenoxacin was titrated using distilled water to the following concentrations: 4,000, 2,000, 1,000, 400, 200, and 100 microg/0.1 mL. Each concentration was injected intravitreally (0.1 mL) into three rabbit eyes. Three control eyes were injected with 0.1 mL of balanced saline solution. All animals were examined before and after injection by indirect ophthalmoscopy and slit-lamp biomicroscopy. Electroretinography was performed on all animals before intravitreal injection and 14 days after injection. The animals were examined by indirect ophthalmoscopy and slit-lamp biomicroscopy before they were killed; the eyes were enucleated and examined with light microscopy. RESULTS: No electroretinographic changes or signs of retinal toxicity by slit-lamp examination, indirect ophthalmoscopy, or light microscopy were seen in any eyes 14 days after intravitreal injection of garenoxacin (< or =4,000 microg/0.1 mL). CONCLUSIONS: Garenoxacin injected intravitreally appeared safe at concentrations of < or =4,000 microg/0.1 mL.

Intravitreal toxicity of moxifloxacin.

PURPOSE: To assess the retinal toxicity of various concentrations of intravitreally administered moxifloxacin, a fourth-generation fluoroquinolone. METHODS: Ten New Zealand albino rabbits were divided into five groups. The initial concentration of moxifloxacin (400 mg/250 mL) was titrated using 5% dextrose solution to concentrations (320 microg/0.1 mL, 160 microg/0.1 mL, 100 microg/0.1 mL, and 50 microg/0.1 mL) that were injected intravitreally into 1 eye of each rabbit. Two control eyes were injected intravitreally with 0.1 mL of 5% dextrose solution. All animals were examined before and after injection by indirect ophthalmoscopy and slit-lamp biomicroscopy; electroretinography (ERG) was performed on all animals. The animals were killed, and their eyes were enucleated and examined with light microscopy. RESULTS: Remarkable decreases in ERG findings were noted in the group injected with moxifloxacin at a concentration of 320 microg/0.1 mL. No meaningful ERG changes were observed in eyes injected with moxifloxacin at other concentrations. There were no signs of retinal toxicity during slit-lamp examination, indirect ophthalmoscopy, or light microscopy in any eyes injected with moxifloxacin concentrations of < or =160 microg/0.1 mL. CONCLUSIONS: Intravitreal injection of moxifloxacin at a concentration of < or =160 microg/0.1 mL appeared nontoxic in the rabbit eye.