Efficacy and safety of antifungal additives in Optisol-GS corneal storage medium.
OBJECTIVE
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.


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


METHODS
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.


METHODS
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
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.
Department of Ophthalmology, University of California, San Francisco.
Noelle
N
Layer
Francis I. Proctor Foundation, San Francisco, California.
Vicky
V
Cevallos
SightLife, Seattle, Washington.
Andrew J
AJ
Maxwell
SightLife, Seattle, Washington.
Caroline
C
Hoover
Department of Ophthalmology, University of California, San Francisco2Francis I. Proctor Foundation, San Francisco, California.
Jeremy D
JD
Keenan
Department of Ophthalmology, University of California, San Francisco2Francis I. Proctor Foundation, San Francisco, California4Department of Ophthalmology, San Francisco General Hospital, San Francisco, California.
Bennie H
BH
Jeng
D000666:Amphotericin B / Q000009:adverse effects / Q000494:pharmacology; D000935:Antifungal Agents / Q000009:adverse effects / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D041221:Candida glabrata / Q000187:drug effects; D002177:Candidiasis / Q000382:microbiology / Q000517:prevention & control*; D002452:Cell Count; D002809:Chondroitin Sulfates / Q000009:adverse effects / Q000494:pharmacology*; D015169:Colony Count, Microbial; D045424:Complex Mixtures / Q000009:adverse effects / Q000494:pharmacology; D003315:Cornea; D016895:Culture Media, Serum-Free / Q000009:adverse effects / Q000494:pharmacology; D003911:Dextrans / Q000009:adverse effects / Q000494:pharmacology*; D004338:Drug Combinations; D004340:Drug Contamination / Q000517:prevention & control*; D004728:Endothelium, Corneal / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D005839:Gentamicins / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009926:Organ Preservation; D019188:Organ Preservation Solutions / Q000009:adverse effects / Q000494:pharmacology*; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology; D014019:Tissue Donors; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology; D065819:Voriconazole
D000935:Antifungal Agents; D045424:Complex Mixtures; D016895:Culture Media, Serum-Free; D003911:Dextrans; D004338:Drug Combinations; D005839:Gentamicins; D019188:Organ Preservation Solutions; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D002809:Chondroitin Sulfates; C075736:Optisol; D065819:Voriconazole