Evaluating retinal toxicity of intravitreal caspofungin in the mouse eye.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mojumder
Deb K
DK
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Concepcion
Francis A
FA
Patel
Shil K
SK
Barkmeier
Andrew J
AJ
Carvounis
Petros E
PE
Wilson
John H
JH
Holz
Eric R
ER
Wensel
Theodore G
TG
D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D000077336:Caspofungin; D004353:Drug Evaluation, Preclinical; D054714:Echinocandins / Q000633:toxicity*; D004596:Electroretinography / Q000187:drug effects; D058449:Intravitreal Injections; D055666:Lipopeptides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin