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Original Investigation | Laboratory Sciences

Efficacy and Safety of Antifungal Additives in Optisol-GS Corneal Storage Medium

Noelle Layer, MD1; Vicky Cevallos, MT2; Andrew J. Maxwell, CEBT3; Caroline Hoover, CEBT3; Jeremy D. Keenan, MD, MPH1,2; Bennie H. Jeng, MD, MS1,2,4
[+] Author Affiliations
1Department of Ophthalmology, University of California, San Francisco
2Francis I. Proctor Foundation, San Francisco, California
3SightLife, Seattle, Washington
4Department of Ophthalmology, San Francisco General Hospital, San Francisco, California
JAMA Ophthalmol. 2014;132(7):832-837. doi:10.1001/jamaophthalmol.2014.397.
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Importance  Optisol-GS, the most common corneal storage medium in the United States, contains antibacterial but no antifungal supplementation. Most postkeratoplasty endophthalmitis and keratitis cases are now of a fungal origin.

Objective  To assess the efficacy and safety of voriconazole and amphotericin B in reducing Candida species contamination of Optisol-GS under normal storage conditions.

Design, Setting, and Participants  In vitro laboratory study using 15 pairs of research-grade donor corneas and 20-mL vials of Optisol-GS.

Interventions  Twenty vials of Optisol-GS were supplemented with either voriconazole at 1×, 10×, 25×, or 50× minimum inhibitory concentration (MIC) or amphotericin B at 0.25×, 0.5×, 1×, or 10× MIC. Known concentrations of Candida albicans and Candida glabrata were each added to a set of vials. Safety studies were performed by separating 15 pairs of donor corneas into unsupplemented Optisol-GS or Optisol-GS plus an antifungal.

Main Outcomes and Measures  Efficacy outcomes were viable fungal colony counts determined from samples taken on days 2, 7, and 14 immediately after removal from refrigeration and after warming to room temperature for 2 hours. Safety outcomes included percentage of intact epithelium and endothelial cell density on days 0, 7, and 14, as well as percentage of nonviable endothelial cells by vital dye staining on day 14.

Results  Growth of C albicans and C glabrata was observed in all voriconazole-supplemented vials. In contrast, there was no growth of either organism in amphotericin B–supplemented vials, except at 0.25× and 0.5× MIC on day 2, when viable counts of C glabrata were reduced by 99% and 96%, respectively. Compared with paired controls, with the exception of Optisol-GS plus amphotericin B at 10× MIC, donor corneas in supplemented Optisol-GS appeared to have no difference in endothelial cell density reduction, percentage of intact epithelium, or percentage of nonviable endothelial cells.

Conclusions and Relevance  The addition of amphotericin B to Optisol-GS may significantly improve activity against contamination with Candida species, the primary cause of fungal infection after corneal transplantation. This study found significant endothelial toxic effects at the maximal concentration of amphotericin B.

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Figure 1.
Time-Kill Plot or Colony Concentration Over Time in Vials Inoculated With Candida albicans

Note that all amphotericin B values overlap and thus appear as one line. MIC indicates minimum inhibitory concentration.

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Figure 2.
Time-Kill Plot or Colony Concentration Over Time in Vials Inoculated With Candida glabrata

Note that most amphotericin B values overlap. MIC indicates minimum inhibitory concentration.

Graphic Jump Location

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