Preventive treatment of allograft rejection after endothelial keratoplasty: A systematic review and meta-analysis

Purpose: To evaluate the efficacy of preventive treatment against allograft rejection after endothelial keratoplasty (EK), we conducted a systematic review and meta-analysis. 

Method: PubMed, Cochrane Library, Embase and ScienceDirect databases were searched until May 2021. We computed a random-effect meta-analysis on graft rejection rate stratified by the intervention (i.e. Descemet membrane EK (DMEK) and Descemet stripping (Automated) EK (DS(A)EK) or ultrathin (UT)-DSAEK), and postoperative treatment. Meta-regressions were performed to compare intervention, treatment and influence of putative confusion factors. 

Results: We included 49 studies and 12 893 EK (6867 DMEK and 6026 DS(A)EK/UT-DSAEK). Topical steroids were merged in two efficacy regimens: standard steroids (prednisolone acetate 1% or dexamethasone 0.1%) and soft steroids (fluorometholone 0.1% or loteprednol etabonate 0.5%). Globally, DMEK had a lower graft rejection rate than DS(A)EK/UT-DSAEK (coefficient − 3.3, 95 CI, −4.60 to −1.90; p < 0.001). No significant differences were observed between standard and soft steroids to prevent graft rejection after DMEK. After EK, the rate of ocular hypertension was 20% (95 CI, 14 to 26%) with the use of standard steroids and 7% (5 to 9%) with soft steroids. Comparisons of treatments were not feasible in DS(A)EK/UT-DSAEK due to a lack of studies. 

Conclusions: Descemet membrane endothelial keratoplasty (DMEK) has less risk of graft rejection compared with DS(A)EK/UT-DSAEK. Furthermore, soft steroids seemed to be a valuable alternative to standard steroids to prevent graft rejection after DMEK, involving a safe profile against ocular hypertension. Further studies are needed to compare other drugs in the prevention of graft rejection after EK.