Development and Clinical Validation of the DMEK Risk and Outcome Prediction (DROP) Score: A Dynamic Temporal Machine Learning Framework

<b>Background/Objectives:</b> To develop and validate the DMEK Risk and Outcome Prediction (DROP) Score-a benchmarking model integrating patient, donor, surgical, and center-specific parameters for individualized risk assessment following DMEK. <b>Methods:</b> The DROP Score comprises four subscores, namely the Patient Risk Profile (PRP), Donor Tissue Quality (DTQ), Surgical Complexity Index (SCI), and Center Performance Factor (CPF), with literature-derived weights (α = 0.40, β = 0.25, γ = 0.20, δ = 0.15) validated by sensitivity analysis (K = 0.82-0.91). Clinical validation included 76 DMEK eyes and 89 controls (2019-2023). Machine learning models utilized EfficientNetV2B3 transfer learning with Random Forest classifiers and patient-level data partitioning. IVCM imaging comprised 6200 images. <b>Results:</b> The mean DROP Score was 39.35 ± 7.61 (Moderate: 92.1%; High: 7.9%). High-risk patients showed worse 12-month BCVA (0.50 vs. 0.31 logMAR) and higher poor prognosis rates (50.0% vs. 34.3%). The DROP Score showed significant correlations with BCVA (<i>r</i> = 0.305, <i>p</i> = 0.007) and ECD (<i>r</i> = -0.352, <i>p</i> = 0.002). Tissue classification accuracy reached 96.2%. Diabetes mellitus emerged as the strongest prognostic factor (OR: 4.34, <i>p</i> = 0.012), followed by hypertension (OR: 2.65, <i>p</i> = 0.078). <b>Conclusions:</b> The DROP Score provides transparent, individualized DMEK risk assessment. Diabetes mellitus and hypertension emerged as dominant systemic prognostic factors, while rebubbling showed no adverse impact on long-term outcomes. Complete four-domain validation requires ongoing prospective data collection.