The Biologic Character of Donor Corneal Endothelial Cells Influences Endothelial Cell Density Post Successful Corneal Transplantation

PURPOSE: Corneal endothelial cell density (ECD) gradually decreases after corneal transplantation by unknown biologic, biophysical, or immunologic mechanism. Our purpose was to assess the association between donor corneal endothelial cell (CEC) maturity in culture and postoperative endothelial cell loss (ECL) after successful corneal transplantation. DESIGN: Prospective cohort study. PARTICIPANTS: This cohort study was conducted at Baptist Eye Institute, Kyoto, Japan, between October 2014 and October 2016. It included 68 patients with a 36-month follow-up period who had undergone successful Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty. METHODS: Human CECs (HCECs) from remaining peripheral donor corneas were cultured and evaluated for maturity by surface markers (CD166(+), CD44(−/dull), CD24(−), and CD105(−)) using fluorescence-activated cell sorting. Postoperative ECD was assessed according to the mature-differentiated HCEC contents: high-maturity group: > 70%, middle-maturity group: 10% to 70%, low-maturity group: < 10%. The successful rate of ECD maintained at 1500 cells/mm(2) at 36 months postoperative was analyzed using the log-rank test. MAIN OUTCOME MEASURES: Endothelial cell density and ECL at 36 months postoperative. RESULTS: The 68 included patients (mean [standard deviation] age 68.1 [13.6] years, 47.1% women, 52.9% DSAEK). The high, middle, and low-maturity groups included 17, 32, and 19 eyes, respectively. At 36 months postoperative, the mean (standard deviation) ECD significantly decreased to 911 (388) cells/mm(2) by 66% in the low-maturity group, compared with 1604 (436) by 40% and 1424 (613) cells/mm(2) by 50% in the high and middle-maturity groups (P < 0.001 and P = 0.007, respectively) and the low-maturity group significantly failed to maintain ECD at 1500 cells/mm(2) at 36 months postoperative (P < 0.001). Additional ECD analysis for patients who underwent DSAEK alone displayed a significant failure to maintain ECD at 1500 cells/mm(2) at 36 months postoperative (P < 0.001). CONCLUSIONS: The high content of mature-differentiated HCECs expressed in culture by the donor peripheral cornea was coincident with low ECL, suggesting that a high-maturity CEC content predicts long-term graft survival. Understanding the molecular mechanism for maintaining HCEC maturity could elucidate the mechanism of ECL after corneal transplantation and aid in developing effective interventions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.