Evaluating retinal toxicity of intravitreal caspofungin in the mouse eye

• Published in: Investigative ophthalmology & visual science Vol. 51; no. 11; pp. 5796 - 5803
• Main Authors: Mojumder, Deb K, Concepcion, Francis A, Patel, Shil K, Barkmeier, Andrew J, Carvounis, Petros E, Wilson, John H, Holz, Eric R, Wensel, Theodore G
• Format: Journal Article
• Language: English
• Published: United States Association for Research in Vision and Ophthalmology, Inc 01.11.2010
• Subjects: Animals; Antifungal Agents - toxicity; Drug Evaluation, Preclinical; Echinocandins - toxicity; Electroretinography - drug effects; Intravitreal Injections; Lipopeptides; Male; Mice; Mice, Inbred C57BL; Retina - drug effects; Retina - pathology; Retinal Ganglion Cells - drug effects
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.10-5541

Caspofungin is a synthetic echinocandin antifungal agent that inhibits the synthesis of β(1,3)-D-glucan, an essential component of the cell wall of susceptible Aspergillus and Candida species. In this study, retinal toxicity was determined after intravitreal injection of caspofungin in a mouse model to assess its safety profile for the treatment of fungal endophthalmitis. Caspofungin acetate was injected intravitreally in the left eyes of male C57BL/6 mice, with final vitreal concentrations corresponding to 0.41, 1.2, 2.5, 4.1, and 41 μM (five mice per cohort). A total of 25 age-matched male C57BL/6 mice injected with balanced salt solution were used as control subjects (five for each of the five different caspofungin acetate concentrations). Electroretinograms (ERGs) were recorded 7 weeks after the injections, and the injected eyes were examined histologically. Mice injected with caspofungin at vitreal concentrations from 0.41 to 4.1 μM did not have significant alterations in their ERG waveforms, and their retinas had no detectable morphologic changes or loss of cells. At the vitreal concentration of 41 μM, caspofungin reduced the amplitudes of the a-waves, b-waves, and scotopic threshold responses of the ERG and also produced a decrease in the number of cells in the ganglion cell layer. Caspofungin is a safe antifungal agent at vitreal concentrations of 0.41 to 4.1 μM in mice and consequently shows promise for the treatment of fungal endophthalmitis in humans. Much higher doses produce toxicity and should not be used.