Preloaded Descemet membrane endothelial keratoplasty: A systematic and descriptive review of global experimental and clinical outcomes.

Preloaded Descemet membrane endothelial keratoplasty (plDMEK), in which eye-bank validated donor tissues are prepared, folded, and loaded into delivery devices prior to shipment, has emerged as a promising strategy to standardize and expand access to endothelial keratoplasty. Protocols developed with both endothelium-in (endo-in) and endothelium-out (endo-out) loading configurations have shown to improve surgical efficiency, reproducibility, and tissue utilization while lowering procedural barriers. We compiled current laboratory and clinical evidence on plDMEK and compared endo-in versus endo-out techniques to inform best practices. Following PRISMA guidelines, studies published between June, 2016, and August, 2025, were identified through PubMed, Scopus, Web of Science, and Google Scholar. Thirty-nine studies met inclusion criteria (19 clinical, 20 laboratory). Across 1420 clinical eyes, the overall sample size-weighted rebubbling rate was 25.5%; with rates of 30.4% for endo-in and 19.3% for endo-out grafts. Both configurations produced meaningful visual improvement from baseline (0.18 logMAR for endo-in, 0.12 logMAR for endo-out; p = 0.31) with endothelial cell loss (ECL) of 38% (endo-in) and 32% (endo-out) (p = 0.33) at 12 months. Laboratory studies showed a pooled ECL of 10.2% (9.4% endo-in, 11% endo-out; p = 0.4112) after storing in the delivery device for up to five days. Both approaches appear to be reliable, safe, and clinically acceptable methods for graft preparation and delivery. While endo-out technique shows a trend toward lower post operative rebubbling compared to endo-in, study heterogeneity underscores the need for standardized reporting, longer follow-up, and direct comparative trials to guide global clinical adoption.