Objective To examine the effect of donor age and other perioperative factors on long term endothelial cell loss after penetrating keratoplasty (PKP) Design Multi-center, prospective, double-masked clinical trial Participants 176 participants from the Cornea Donor Study cohort who had not experienced graft failure 10 or more years after PKP for a moderate risk condition (principally Fuchs’ dystrophy or pseudophakic/aphakic corneal edema) Methods Corneas from donors 12 to 75 years old were assigned to participants using a randomized approach, without respect to recipient factors. Surgery and post-operative care were performed according to the surgeons’ usual routines. Images of the central endothelium were obtained preoperatively and at intervals for ten years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD). Main Outcome Measure Endothelial cell density at 10 years Results Among study participants with a clear graft at 10 years, the 125 who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 76%, resulting in a 10-year median ECD of 628 cells/mm2 (interquartile range, 522-850), whereas the 51 who received a cornea from a donor 66 to 75 years old experienced a cell loss of 79%, resulting in a median 10-year ECD of 550 cells/mm2 (interquartile range, 483-694) (P adjusted for baseline ECD=0.03). In addition to younger donor age, higher ECD values were significantly associated with higher baseline ECD (P<0.001) and larger donor tissue size (P<0.001). Forty-two (24%) of the 176 participants had an ECD below 500 cells/mm2 at 10 years and only 24 (14%) had an ECD above 1,000 cells/mm2. Conclusions Substantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly higher with older donor age. Higher pre-operative ECD and larger donor tissue size are associated with higher ECD at 10 years. Trial Registration NCT00006411

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Purpose: To evaluate agreement between eye banks (EBs) and a reading center on endothelial cell density (ECD) determinations in the Cornea Preservation Time Study. Methods: The Cornea Image Analysis Reading Center (CIARC) performed variable frame image analysis on EB-obtained–preoperative central endothelial images (after lamellar dissection for Descemet stripping automated endothelial keratoplasty by the EBs or before shipping, if surgeon prepared) to determine ECD. The EBs performed their usual method of ECD determination. The CIARC and EBs also provided ECD determinations from screening central endothelial images taken by the EBs during donor evaluation. Two independent masked CIARC readers determined ECD with measurements averaged. Results: The mean preoperative ECD was 15 cells/mm2 greater by the EBs than by CIARC (N = 1286, P < 0.001) with 95% limits of agreement of (−644, 675 cells/mm2). The limits of agreement in preoperative ECD were wider in the After-Lamellar-Dissection Group (−687, 683 cells/mm2) than in the Before Shipping Group [(−505, 633 cells/mm2); P = 0.03]. The EBs-determined preoperative ECD was within 10% of the CIARC-determined ECD for 886 (69%) image sets, with 236 (18%) higher by >10% and 164 (13%) lower by >10%. Excellent agreement appeared between the EBs and CIARC when 100–300 cells could be analyzed in contrast to <100 cells (SD = 308 cells/mm2 vs. SD = 603 cells/mm2; P < 0.001). Conclusions: The mean ECD by the EBs and CIARC were similar, but there was considerable variability between determinations for individual corneas. Agreement improved between the 2 measurements when more than 100 cells were able to be analyzed.

Purpose: To determine the cost-effectiveness of amphotericin B supplementation, we analyzed both current costs to treat postendothelial keratoplasty (EK) fungal infections and potential costs associated with amphotericin B supplementation. Methods: We collected 19 US cases of post-EK fungal eye infections from the published literature and assessed the associated costs from the literature. A survey of surgeons was also conducted with questions regarding their experiences in managing these infections. Results: We estimated that the costs to diagnose, manage, and treat post-EK fungal keratitis and post-EK fungal endophthalmitis are USD $21,113 and $34,850, respectively. The largest portion of the costs can be attributed to the need for additional surgical management, which is required in 79% of the cases. We estimated the total cost of amphotericin B supplementation to be $44.39 per graft with use of conventional amphotericin B and conservative assumptions regarding supplementation processes. Cost-effectiveness analysis demonstrated that amphotericin B supplementation is cost-effective at $100,000 per quality-adjusted life-year level only if amphotericin B supplementation can prevent more than 69.62% of post-EK fungal infections, assuming the incidence of post-EK fungal infection remains at the level it was between 2012 and 2017. Conclusions: We found that amphotericin B supplementation can be cost-effective under conservative assumptions if it is moderately effective in preventing post-EK fungal infections.

Postmortem HbA1c testing is feasible with current eye bank procedures and is reflective of glycemic control of donors during 90 days before death. HbA1c testing could potentially be a useful adjunct to review of the medical history and records for donor assessment for endothelial keratoplasty suitability and long-term graft success.

Purpose: The purpose of this study was to determine the safety of long-term storage and shipping of prestripped, prestained, and preloaded Descemet membrane endothelial keratoplasty (p3DMEK) grafts. Methods: A total of 33 cadaveric corneas were prestripped, prestained, and preloaded using modified Jones tube injectors as p3DMEK. The corneas were masked to groups that were prepared <9 hours (control), 48 hours, and 72 hours before unloading and analysis. The 48- and 72-hour tissues were shipped by airfreight on each day before arrival to simulate domestic and international shipping. The corneas were then stained using Calcein AM vital dye (Molecular Probes, Eugene, OR) and imaged using an inverted confocal microscope. Primary outcome measures were endothelial cell loss (ECL, %) and sustainability of staining. MetaMorph software (Molecular Devices, Downingtown, PA) was used to quantify ECL, and staining was evaluated subjectively using all-or-none rating. Results: There was no difference in the mean ECL for the control, 48-hour, and 72-hour groups, which were 25.1% ± 8.8%, 26.4% ± 17.5%, and 19.2% ± 11.5%, respectively (P = 0.45; Kruskal–Wallis test). In all tissues of each group, no loss of staining was identified at each time point of analysis. Conclusions: ECL in p3DMEK tissue prepared 48 and 72 hours in advance and shipped using standard methods is similar to that in p3DMEK tissue prepared on the same day. These findings support the safety of domestic and international shipping of p3DMEK grafts.

Clostridial endophthalmitis is an aggressive rapidly progressive infection with potentially poor visual outcomes that can be transmitted from infected corneal allografts. Further investigation is needed to clarify the role of anaerobic donor rim cultures and the donor risk factors associated with recovering corneal allograft tissue contaminated with C. perfringens.

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