Efficacy of Immunosuppressants in High Rejection Risk Keratoplasty: A Meta-Analysis of Comparative Studies

PURPOSE To evaluate the prophylactic effects of immunosuppressants in corneal graft rejection after high-risk penetrating keratoplasty. METHODS We searched PubMed, Embase, and the Cochrane Library for comparative studies published between 1989 and 2019 that evaluated the efficacy of immunosuppressants for high-risk corneal graft. The primary outcomes were the 1- and 3-year rejection rates. A fixed-effects or random-effects model was used on the basis of the I2 value, and the results were reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Topical tacrolimus (FK506) was more effective than topical cyclosporine A (CsA) at reducing the 1-year graft rejection rate (OR: 0.17; 95% CI, 0.08-0.37, P<0.01). However, the combination of steroid with either topical FK506 (OR: 0.4; 95% CI, 0.16-1.04, P = 0.09) or CsA (OR: 0.74; 95% CI, 0.32-1.71, P= 0.48) did not show significant superiority in preventing immune rejection compared with steroid monotherapy. Mycophenolate mofetil (MMF) was more effective than CsA at reducing the 1-year graft rejection rate (OR: 2.67; 95% CI, 1.50-4.76, P<0.01). However, MMF was not significantly superior to CsA at reducing the 3-year graft rejection rate (OR: 1.21; 95% CI, 0.45-3.25, P = 0.71). For reducing the 1-year rejection rate, MMF (OR: 0.12; 95% CI, 0.03-0.39, P < 0.01) and CsA (OR: 0.28; 95% CI, 0.10-0.76, P = 0.01) were each more effective than the control groups. CONCLUSIONS FK506 eye drops, MMF, and systemic CsA were considered to be promising management to prevent rejection in high-risk penetrating keratoplasty in the present study.