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Published on: February 14, 2018
Efficacy and safety of antifungal additives in Optisol-GS corneal storage medium
Noelle Layer1, Vicky Cevallos2, Andrew J Maxwell3
1Department of Ophthalmology, University of California, San Francisco.
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.
Insights
Adding amphotericin B to Optisol-GS corneal storage medium may reduce fungal contamination. However, high concentrations of amphotericin B showed endothelial toxicity in this study.
Area of Science:
- Ophthalmology
- Mycology
- Microbiology
Background:
- Optisol-GS, a common corneal storage medium, lacks antifungal agents.
- Fungal infections are a growing concern post-keratoplasty, with Candida species being a primary cause.
Purpose of the Study:
- To evaluate the efficacy and safety of voriconazole and amphotericin B in preventing Candida contamination in Optisol-GS.
- To assess the impact of these antifungals on donor cornea integrity.
Main Methods:
- An in vitro study using donor corneas and Optisol-GS.
- Supplementation of Optisol-GS with varying concentrations of voriconazole or amphotericin B.
- Exposure to Candida albicans and Candida glabrata, with subsequent fungal colony counts and corneal tissue analysis.
Main Results:
- Voriconazole did not inhibit Candida growth in Optisol-GS.
- Amphotericin B effectively prevented fungal growth, except at very low concentrations on day 2.
- Corneal endothelial cell density and epithelial integrity remained largely unaffected, except at the highest amphotericin B concentration.
Conclusions:
- Amphotericin B shows promise for enhancing Optisol-GS antifungal activity against Candida species.
- Further research is needed to determine optimal, non-toxic concentrations for clinical use.
- This could reduce fungal infections following corneal transplantation.
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