Diabetes Endothelial Keratoplasty Study (DEKS): Impact of Diabetes and Other Predictors on Corneal Transplant Endothelial Cell Loss and Success

Project Summary The proposed Diabetes Endothelial Keratoplasty Study (DEKS) Renewal will follow up from the initial findings of the DEKS, driving evidence-based decisions regarding use of corneal tissue from donors with diabetes for Descemet membrane endothelial keratoplasty (DMEK), the leading form of endothelial keratoplasty in the US. There remains the need to definitively resolve the discrepant findings regarding the use of diabetic donor tissue to guide the corneal transplant community. While we hypothesize that overall non-diabetic corneas are superior, it is unlikely that all donors with diabetes are inferior. Rather, based on preclinical and DMEK eye bank stripping data, we presume that the extremes of diabetes severity in donors drive the adverse effects on DSAEK outcomes that our group noted in the Cornea Preservation Time Study (CPTS) where diabetes in donors and recipients was not collected systematically. In the current DEKS, we seek to determine graft success varies between donor subgroups predefined by presence or absence of diabetes as well as various diabetes severity scales after 1 year of follow-up which we expect will be welcomed findings by eye banks and corneal surgeons guiding them to avoid inefficient distribution of inferior tissue for DMEK. However, the current DEKS, with follow-up limited to 1 year, does not address long term endothelial cell loss (ECL) and accompanying graft failure of diabetic vs non-diabetic donors as well as the recipient diabetes effect. Nor does it examine long term effects of diabetes severity and other predictors (genetic) on ECL and graft failure. The renewal of the DEKS would address this by a powered analysis of long-term ECL out to 5 years as a marker for graft survival in the first specific aim while exploring impact on graft failures in the second specific aim. The third specific aim in the renewal of DEKS will be continuation of the third specific aim in DEKS, exploring the relationship of severity of diabetes in the donor (as measured by eye bank-determined diabetes risk categorization scores, post-mortem HbA1c, and skin AGEs and oxidation markers), and in the recipient (as measured by diabetes risk categorization scores, and HbA1c). In addition, in the most novel aspect of this renewal, we will explore donor and recipient genetics (mutations in TCF4, other Fuchs dystrophy genes, and diabetes polygenic risk scores) on ECL and graft failure 5 years following DMEK. These long-term insights on the diabetic donor and associated graft outcomes as well as recipient diabetic status and Fuchs genetics will provide further guidance to the eye banking and corneal transplant surgeon community on the use of an increasing number of diabetics in the corneal donor pool and increasing number of diabetics in recipients also affected by Fuchs Dystrophy.