Purpose This retrospective cohort study assessed the evolution of corneal transplantation and its indications in the last 21 years (2000–2020) in a specialized ophthalmology department in a tertiary referral center in France. Methods The surgical techniques and indications, patient age and sex, and postoperative best-corrected visual acuity (BCVA) 6 months after keratoplasty were extracted. Results In total, 1042 eyes underwent keratoplasty in 2000–2020. Annual numbers of corneal transplantations increased by 2.2-fold. Penetrating keratoplasty (PKP) was the sole technique for the first 11 years. Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) were introduced in 2011 and 2014, respectively. Cases of both quickly increased, accounting for 28% and 41% of cases in 2015–2020, respectively. Eventually, DSAEK and DMEK were respectively used for most pseudophakic bullous keratopathy (PBK) and all Fuchs endothelial cell dystrophy (FECD) cases. PKP cases declined to 27%. Deep anterior lamellar keratoplasty (DALK) was rare (3% of all cases). These changes associated with rises in PBK and particularly FECD cases, and a strong decline in keratoconus, causing FECD, PBK, and keratoconus to move from being the 4th, 1st, and 3rd most common indications to the 1st, 2nd, and 6th, respectively. On average, BCVA improved by 0.1–0.3 logMAR. Patient age dropped steadily over time. Female predominance was observed. Conclusions The invention of DSAEK and then DMEK precipitated an enormous change in clinical practice and a large expansion of keratoplasty to new indications. This study confirms and extends previous findings in other countries.

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