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H. Gao, M.E. Pennesi, M. Iyer, X. Qiao, E.R. Holz, W.F. Mieler; Safety of Intravitreal Moxifloxacin: Electroretinographic and Histopathologic Study . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5553.
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Purpose: Moxifloxacin, a new fourth generation fluoroquinolone recently approved by the FDA, is a potent antibiotics used for systemic infection. To determine whether moxifloxacin can be safely used as an intra–ocular agent to treat bacterial endophthalmitis, retinal toxicity of intravitreal moxifloxacin was studied using electro–retinographic (ERG) and histopathologic examinations in animal models. Methods: Moxifloxacin solutions were serially diluted and injected intravitreally into eyes of normal adult C57/BL6 mouse so that the final intravitreal concentrations were 5 µg, 25 µg, 50 µg, 100 µg, and 500 µg/ml (N = 5 for each concentration group). The drug vehicle of the same volume was injected into the fellow eyes of each animal as controls. Four weeks after injections, electroretinograms (ERG) were measured, and animal eyes were subsequently enucleated for histological examination. To confirm the results from mouse study, intravitreal injection of moxifloxacin was also performed in five pieces of pigmented Dutch Belted rabbits, and the final intravitreal moxifloxacin concentration was 150 µg/ml. ERG and histology studies were performed 4 weeks after injection. Results: In ERG study, no significant difference could be detected in either scotopic or photopic response between control eyes and moxifloxcin injected eyes of any dosage in mouse or in rabbit. Student t–test and ANOVA were used for statistical studies. Histological examination did not reveal any retinal abnormality in the mouse eyes with 5 to 100 µg/ml, or in the rabbit eyes with 150 µg/ml, of intravitreal moxifloxacin. In the mouse eyes with 500 µg/ml moxifloxacin, occasional small foci of retinal necrosis were observed in the outer retina, suggesting very isolated focal retinal toxicity at this high concentration of moxifloxacin. Conclusions: Our results demonstrate that intravitreal moxifloxacin of up to 100 µg/ml in mouse or of 150 µg/ml in rabbit causes no ERG change or histological abnormality in retina. Since this concentration (100 µg/ml to 150 µg/ml) is far beyond the minimum inhibitory concentration (MIC) of most moxifloxacin–sensitive bacteria, this indicates that moxifloxacin is a very safe anti–bacterium agent for intravitreal injection in rodent and in rabbit and may be employed in the treatment of human bacterial endophthalmitis following further study.
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