Comparison of micafungin and fluconazole for experimental Candida keratitis in rabbits.

PURPOSE: To evaluate the efficacy of subconjunctival injection of micafungin in the treatment of experimental Candida albicans keratitis in rabbits compared with fluconazole. METHODS: In 1 eye of 24 New Zealand white rabbits, C. albicans (5 x 10 yeast cells) was inoculated in the corneal stroma. The animals were randomly assigned to 3 groups and received subconjunctival injection of 0.5 mL of 0.1% micafungin, 0.2% fluconazole, or physiologic saline once a day for 3 weeks. The eyes were examined slit-lamp biomicroscopically and histopathologically. The clinical course of fungal keratitis was compared among the 3 groups. In another 36 rabbits, a microbiological examination was performed using a quantitative isolate recovery technique, and the numbers of colony-forming units were compared among groups. RESULTS: The clinical scores were significantly lower in the micafungin group than in the other 2 groups throughout the study period (P < 0.0001 approximately P = 0.0027, Bonferroni multiple comparison). The fluconazole group showed significantly lower clinical scores than the saline group on day 18 (P = 0.0343). At the end of the study period, there were significant differences between the saline and micafungin groups (P < 0.0001), the saline and fluconazole groups (P = 0.0072), and the fluconazole and micafungin groups (P = 0.0013). Histopathologically, similar results were obtained. Moreover, the results of the microbiological examination nearly matched the clinical and histopathologic findings. CONCLUSIONS: Subconjunctival administration of micafungin was effective in the treatment of experimental Candida keratitis. Local application of micafungin to the eye would be a feasible treatment option for clinical fungal keratitis.

Toxicological evaluation of micafungin ophthalmic solution in rabbit eyes.

There have been no reports of the topical application of micafungin to the eye. The aim of this study was to evaluate the safety of topical instillation of 0.1% micafungin ophthalmic solution in rabbit eyes. In New Zealand white rabbits (n = 6), 50 microL of 0.1% micafungin solution was topically instilled to 1 eye, and 50 microL of sterile saline was applied to the other eye. Both eyedrops were administered hourly from 7 A.M. for 7 days. Measurements were conducted on corneal thickness, intraocular pressure, endothelial cell density, and lactate dehydrogenase (LDH) activity of tear samples. The eyes were examined slit-lamp biomicroscopically and histopathologically. Topical micafungin application for 1 week did not induce any changes in intraocular pressure, endothelial cell density, and tear LDH. Corneal thickness after instillation was slightly, but significantly, smaller in the micafungin group than in the control group (P = 0.0156, paired t test), but this difference disappeared within 24 hours after the final instillation. Biomicroscopy and histopathology revealed no significant toxic influence of micafungin application on the cornea. Topical instillation of micafungin solution had no apparent toxicity to the cornea. These results warrant future studies on the efficacy of micafungin ophthalmic solution against corneal fungal infection.