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Noelle Layer, Vicky Cevallos, Andrew Maxwell, Caroline Ulrickson, Jeremy Keenan, Bennie Jeng; Efficacy and Safety of Voriconazole and Amphotericin B as Additives in Optisol-GS Corneal Storage Media Against Candida Species. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2897.
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© ARVO (1962-2015); The Authors (2016-present)
Optisol-GS is the most commonly used corneal storage medium in the United States; however, it currently does not include an antifungal additive. The purpose of this study was to assess the efficacy and safety of voriconazole and amphotericin B in reducing Candida contamination of Optisol-GS under normal storage conditions.
Vials of Optisol-GS were supplemented with either voriconazole at 1x, 10x, 25x, or 50x minimum inhibitory concentration (MIC) or amphotericin B at 0.25x, 0.5x, 1x, or 10x MIC. Unsupplemented control groups were also used. Isolates of C. albicans and C. glabrata were each added to a set of vials, which were refrigerated at 4 degrees C. On days 2, 7, and 14, samples were taken to determine viable colony counts immediately after removal from refrigeration and after warming to room temperature for 2 hours. Safety studies were performed by separating 15 pairs of donor corneas into unsupplemented Optisol-GS or Optisol-GS plus voriconazole at 50x MIC, or Optisol-GS plus amphotericin B at 0.25x, 0.5x, 1x, or 10x MIC. Corneal thickness via pachymetry and endothelial cell density (ECD) via specular microscopy were determined at days 0 and 7.
Growth of C. albicans and C. glabrata in Optisol-GS was observed at each concentration of voriconazole. In contrast, with supplementation of amphotericin B, there was no growth of C. albicans by day 2 or C. glabrata by day 7 at all concentrations. Viable counts of C. glabrata were reduced by 99% and 96% with amphotericin B supplementation at 0.25x and 0.5x MIC, respectively, on day 2. Compared to paired controls, there was a significant reduction in ECD with Optisol-GS plus amphotericin B at 10x MIC (P = 0.04), a similar trend with amphotericin B at 1x (P = 0.07), and no significant difference at other concentrations.
The addition of amphotericin B, but not voriconazole, to Optisol-GS may significantly improve activity against contamination with Candida spp., a major cause of fungal endophthalmitis after corneal transplantation. While there appears to be toxicity to the corneal endothelium at the maximal concentration of amphotericin B studied, there is no evidence for toxicity at the lower doses. A larger study is warranted to confirm these findings.
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