Systemic mycophenolate mofetil in comparison with systemic cyclosporin A in high-risk keratoplasty patients: 3 years' results of a randomized prospective clinical trial

Background: With the use of systemic cyclosporin A (CsA), graft prognosis a fter high-risk penetrating keratoplasty has improved considerably. However, the application of CsA is limited owing to a variety of severe side effect s. In this prospectively randomized study mycophenolate mofetil (MMF), a sa fe and efficient immunosuppressive medication after renal transplantation, was compared with CsA after high-risk penetrating keratoplasty. Methods: Tw enty-nine high-risk keratoplasty patients were treated with MMF 2 x 1 g dai ly; another 27 patients received CsA, aiming at blood trough levels of 120- 150 ng/ml. Systemic immunosuppression was scheduled for 6 months. In both g roups oral corticosteroids (fluocortolone 1 mg/kg) were administered for 3 weeks postoperatively. Results: During the first year after operation, no g raft failure was recorded. Two years postoperatively 92%/82% and 3 years po stoperatively 74%/69% of grafts were clear in the MMF and CsA group, respec tively (Kaplan Meier P=0.33, log-rank test). In total, two graft failures w ere recorded in the MMF group and four in the CsA group. Three years postop eratively 53% of the grafts were rejection-free in the MMF group and 73% in the CsA group (Kaplan Meier P=0.46, log-rank test). Eight endothelial immu ne reactions were observed in the MMF group (three under systemic immunosup pression/five thereafter; six mild/two severe) and five in the CsA group (t hree under systemic immunosuppression/two thereafter; three mild/two severe ). Side effects occurred in six patients under MMF and 11 under CsA. Conclu sions: Concerning efficacy, no statistically significant difference between systemic MMF and systemic CsA administered for 6 months after high-risk pe netrating keratoplasty could be shown. Systemic MMF was proven to be at lea st as safe as CsA. The main mechanism in improving graft survival is a shif t from severe to milder endothelial immune reactions, as already demonstrat ed for CsA. Thus, MMF may become an alternative to CsA for immunosuppressio n after penetrating high-risk keratoplasty. About 2 years postoperatively, pharmacologically induced relative immunological tolerance slowly decreases . Therefore, longterm administration of systemic MMF should be evaluated in further studies.