**Background:** Descemet membrane endothelial keratoplasty (DMEK) is a posterior lamellar keratoplasty technique that transplants only Descemet membrane and corneal endothelium, offering faster and better visual recovery with less immune rejection compared to penetrating keratoplasty or Descemet-stripping automated endothelial keratoplasty (DSAEK). However, long-term outcomes beyond 2 years are limited, with only five groups reporting results. This study aimed to assess 5-year clinical outcomes, complications, and graft survival in a consecutive, unselected real-world cohort.
**Methods:** This retrospective single-center cohort study included all consecutive adult patients who underwent first-time DMEK (pseudophakic-DMEK or triple-DMEK) between March 2014 and March 2018 at the Metz-Thionville Regional Hospital Center (France). The first five eyes were excluded to limit learning-curve effects. All surgeries were performed by the same experienced surgeon. Grafts were prepared from organ-cultured donor corneas with requested endothelial cell density (ECD) >2000 cells/mm². Postoperatively, patients received topical antibiotic-corticosteroid for 4 weeks, then long-term low-dose corticosteroid. Follow-up occurred at 1, 8, and 15 days, then at 1, 3, 6, and 12 months, and annually thereafter. Best-corrected visual acuity (BCVA) was measured using Monoyer chart and converted to logMAR. Central corneal thickness (CCT) was measured by non-contact ultrasonic pachymetry, and ECD by specular microscopy. Graft survival was estimated by Kaplan-Meier analysis. Changes in BCVA, ECD, and CCT were assessed using Wilcoxon signed rank test. Seven eyes with preoperative vision-limiting comorbidities were excluded from BCVA analyses.
**Key Results:** 107 eyes from 80 patients (mean age 72 years; 67% female) were included. Indications were Fuchs endothelial corneal dystrophy (FECD, 94%), pseudophakic bullous keratopathy (PBK, 3%), and regraft after previous keratoplasty (3%). Mean preoperative BCVA was 0.6 logMAR, mean graft ECD was 2550 cells/mm², and mean CCT was 618 μm. The most common complication was graft detachment requiring rebubbling (18% of eyes); rebubbling was successful in 70% of cases. Thirteen grafts (12%) failed at ≤15 months (7 primary graft failures, 6 secondary graft failures). One allograft rejection occurred at 15 months (1%). Cystoid macular edema occurred in 6% of eyes. Cumulative 5-year graft survival probability was 88% (95% CI: 79–94%). BCVA improved from 0.6 logMAR preoperatively to 0.05 logMAR at 1 year (p<0.0001) and remained stable at 0.0 logMAR at 5 years. At 5 years, 92% of eyes had BCVA ≥20/40, 77% ≥20/25, 57% ≥20/20, and 24% ≥20/17. Donor ECD dropped by 47% at 6 months (to 1350 cells/mm²) and then continued to decrease by 4.0%/year, reaching 900 cells/mm² at 5 years (65% total endothelial cell loss). CCT decreased from 618 μm preoperatively to 551 μm at 5 years (p<0.0001). Loss to follow-up was only 1% at 5 years.
**Clinical Implications:** This study demonstrates that DMEK provides excellent long-term visual outcomes, low complication rates, and high graft survival (88% at 5 years) in a real-world, unselected cohort. The findings are consistent with previous long-term studies, supporting DMEK as a safe and effective first-choice treatment for FECD. The high ongoing endothelial cell loss (4%/year after initial drop) underscores the importance of using grafts with high ECD. The low rate of allograft rejection (1%) confirms the immunological advantage of DMEK. However, the study is limited by its retrospective design, relatively small sample size, and predominance of FECD patients; long-term outcomes in PBK and other indications require further investigation.