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

Abstract

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 PARTICIPANTSIn 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 RELEVANCEThe 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.

Candida Interface Infections After Descemet Stripping Automated Endothelial Keratoplasty

“…Ritterband et al 26 found that adding 100 mg/mL voriconazole to cornea storage medium significantly reduced fungal growth. In contrast, Layer et al, 27 were able to culture C. albicans and C. glabrata from media inoculated with a lower dose of voricazonole (50 mg/mL). However, in samples supplemented with amphotericin B, there was no growth of fungal organisms except at 0.25· and 0.5· minimum inhibitory concentrations.…”

“…However, in samples supplemented with amphotericin B, there was no growth of fungal organisms except at 0.25· and 0.5· minimum inhibitory concentrations. 27 Although corneas destined for PK are also stored in Optisol-GS, there are several distinct opportunities for fungal growth and contamination associated with precut tissue processing for DSAEK when compared with PK. After harvesting, precut tissue is placed in Optisol and stored at 4°C.…”

First Reported Case of Donor Related Candida Endophthalmitis after Descemet Membrane Endothelial Keratoplasty

“…[11-12] Both agents were effective in reducing the incidence of positive cultures. The EBAA has held the position that the low incidence of fungal infections does not warrant the routine use of antifungal medications in storage media.…”

Corneal Infections—Challenges in Diagnosis and Update on Management

“…7,8 In the meantime, a heightened awareness of this condition, along with aggressive treatment should point the practitioner to consider the diagnosis of AK. 9,10 Even when the suspicion is high, confirmation can be difficult as cultures are sometimes unrewarding in terms of a high false negative rate.…”