National Eye Institute Supported Randomized Controlled Trials in Keratoplasty for Endothelial Disorders: Lessons Learned.

Abstract: National Eye Institute (NEI)-funded randomized controlled trials (RCTs) have significantly shaped the modern landscape of keratoplasty for endothelial disorders. Unlike retrospective studies, RCTs have offered the highest level of clinical evidence and have addressed critical questions related to histocompatibility matching, donor and donor tissue characteristics, donor tissue storage, and operative and postoperative factors supporting postoperative endothelial cell health. These RCTs have in turn directly influenced eye banking and keratoplasty practices. The purpose of this review is to 1) summarize the major findings from all of the NEI-sponsored keratoplasty RCTs, including the Collaborative Corneal Transplantation Studies, the Cornea Donor Study and its ancillary study, the Specular Microscopy Ancillary Study, the Cornea Preservation Time Study, as well as the on-going Diabetes Endothelial Keratoplasty Study and the Descemet Endothelial Thickness Comparison Trial; 2) review select keratoplasty RCTs not supported by the NEI; 3) compare findings from these RCTs with those from the major keratoplasty registries; and 4) discuss promising future directions in keratoplasty and eye banking that would lend themselves for RCTs. Collectively, these RCTs have clarified long-standing controversies, validated emerging practices, and will continue to provide the foundation for future innovation in the surgical management of endothelial diseases.