Association Between Fungal Contamination and Eye Bank–Prepared Endothelial Keratoplasty Tissue

Abstract

IMPORTANCE Fungal contamination and infection from donor tissues processed for endothelial keratoplasty is a growing concern, prompting analysis of donor tissues after processing.OBJECTIVE To determine whether eyebank-processed endothelial keratoplasty tissue is at higher risk of contamination than unprocessed tissue and to model eyebank processing with regard to room temperature exposure on Candida growth in optisol-gentamicin and streptomycin (GS) with and without antifungal supplementation. DESIGN, SETTING, AND PARTICIPANTS An examination of the 2013 Eversight Eyebank Study follow-up database for risk factors associated with post-keratoplasty infection identified an increased risk of positive fungal rim culture results in tissue processed for endothelial keratoplasty vs unprocessed tissue. Processing steps at room temperature were hypothesized as a potential risk factor for promotion of fungal growth between these 2 processes. Candida albicans, Candida glabrata, and Candida parapsilosis endophthalmitis isolates were each inoculated into optisol-GS and subjected to 2 different room temperature incubation regimens reflective of current corneal tissue handling protocols. MAIN OUTCOMES AND MEASURESEversight Eyebank Study outcomes and measures were follow-up inquiries from 6592 corneal transplants. Efficacy study outcomes and measures were fungal colony-forming units from inoculated vials of optisol-GS taken at 2 different processing temperatures.RESULTS Donor rim culture results were 3 times more likely to be positive for fungi in endothelial keratoplasty-processed eyes (1.14%) than for other uses (0.37%) (difference, 0.77%; 95% CI, 0.17-.1.37) (P = .009). In vitro, increased room temperature incubation of optisol-GS increased growth of Candida species over time. The addition of caspofungin and voriconazole decreased growth of Candida in a species-dependent manner.CONCLUSIONS AND RELEVANCE Detectable Candida growth in donor rim cultures, associated with a higher rate of post keratoplasty infection, is seen in endothelial keratoplasty tissue vs other uses at the time of transplantation, likely owing in part to eyebank preparation processes extending the time of tissue warming. Reduced room temperature incubation and the addition of antifungal agents decreased growth of Candida species in optisol-GS and should be further explored to reduce the risk of infection.

Incidence and Outcomes of Positive Donor Rim Cultures and Infections in the Cornea Preservation Time Study

“…A possibility is that this rigorous tracking may have promoted greater efficiency and attention to reduce warming times. Previous studies indicating increased donor culture rim positivity in eye bank prepared tissue were single center, 8,9 multi-center/single eye bank, 10 or survey-based 13 unlike the prospective, multi-eye-bank and multi-surgeon CPTS 1 . Additional multi-surgeon, multi-center and multi-eye bank studies are needed to further determine the impact of eye bank prepared DSAEK tissue on donor rim fungal culture rates and fungal infection after DSAEK.…”

“…In a 2017 study utilizing a 2013 database, donor rim cultures were three times more likely to be positive for fungi in EK-processed eyes than for other uses (1.14% vs 0.37%; p=0.009). 10 The leading hypothesis for this increase with EK tissue processed by the eye bank is the need for extended time for tissue warming in order to perform the lamellar dissection and obtain a post-preparation endothelial cell image 10,20 . In contrast, the CPTS data indicate a lower rate of positive fungal donor rim cultures with eye bank prepared tissue as compared to surgeon prepared tissue.…”

“…This finding is similar to other studies with an incidence of 1.1–2.1% for positive donor rim fungal cultures resulting in a rate of up to 7.5% postoperative recipient fungal infections if fungal contaminated tissue was received (Table 4). 6–10,19,25–29 Because of the small number of treated infections in the CPTS, there are insufficient data to determine if treatment in response to a positive fungal or bacterial culture has impact in the prevention or amelioration of infection. These studies have prompted interest in decreasing the risk of donor-to-host transmission of fungal infection by adding antifungal medication to the corneal storage solution at 4–8°C.…”

“…6 Fungal contamination of donor rims occurs in 1–2% of cases while establishment of fungal infections in eyes that received contaminated tissue may occur in up to about 7% of cases. 7–10 Case reports and series highlight the risk of receiving fungal contaminated tissue and the belief that patients receiving donor tissue with fungal positive rim cultures should be prophylactically treated with antifungal therapy. 11,12 Positive donor corneal rim fungal cultures at the time of keratoplasty may be more predictive of infectious keratitis and endophthalmitis as compared to positive bacterial rim cultures.…”

“…7 Finally, a trend towards more post-keratoplasty fungal infections after Descemet’s stripping automated endothelial keratoplasty (DSAEK) with eye-bank-processed donor tissue compared to surgeon-processed donor tissue keratoplasty was noted in an unpublished report by the Medical Advisory Board Subcommittee of the Eye Bank Association (EBAA) (Aldave, personal communication, December 2017), and a 2017 publication showing that there is an increased risk of positive fungal rim cultures in tissue processed by eye banks for endothelial keratoplasty (EK) compared to unprocessed tissue. 10…”