Background: With the use of systemic cyclosporin A (CsA), graft prognosis after high-risk penetrating keratoplasty has improved considerably. However, the application of CsA is limited owing to a variety of severe side effects. In this prospectively randomized study mycophenolate mofetil (MMF), a safe and efficient immunosuppressive medication after renal transplantation, was compared with CsA after high-risk penetrating keratoplasty. Methods: Twenty-nine high-risk keratoplasty patients were treated with MMF 2× 1 g daily; another 27 patients received CsA, aiming at blood trough levels of 120-150 ng/ml. Systemic immunosuppression was scheduled for 6 months. In both groups oral corticosteroids (fluocortolone 1 mg/kg) were administered for 3 weeks postoperatively. Results: During the first year after operation, no graft failure was recorded. Two years postoperatively 92%/82% and 3 years postoperatively 74%/69% of grafts were clear in the MMF and CsA group, respectively (Kaplan Meier P=0.33, logrank test). In total, two graft failures were recorded in the MMF group and four in the CsA group. Three years postoperatively 53% of the Graefe's Arch Clin Exp Ophthalmol

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Background/aims-The requirement for an eVective, minimally toxic immunosuppressive agent remains a major obstacle to performing high risk corneal transplantation. Although therapy with cyclosporin A (CSA) allows superior graft survival, its use is limited because of a wide range of side eVects. Mycophenolate mofetil (MMF) has been shown to be a safe and eVective immunosuppressive agent following renal transplantation. This prospective, randomised clinical trial was carried out to investigate the eYcacy and safety of MMF in preventing corneal allograft rejection. Methods-Recipients of corneal transplants who were at high risk for graft failure were randomly assigned to either CSA or MMF immunosuppressive therapy. CSA was given in doses to achieve whole blood trough levels of 120-150 ng/ml. MMF was given in a daily dose of 2 g. Both therapy groups additionally received oral corticosteroids (fluocortolone 1 mg/kg) which were tapered and discontinued within the first 3 postoperative weeks. Patients were monitored closely for evidence of corneal graft rejection and adverse side eVects. Drug eYcacy was measured, primarily, by the number of patients who experienced at least one episode of clinical graft rejection. Safety analysis focused on reported adverse side eVects and laboratory measurements. Results-41 patients were enrolled in the study. There was no statistically significant diVerence between the two groups. 20 patients received CSA and 21 patients received MMF. Two patients in each group showed evidence of acute graft rejection which could be treated eVectively by corticosteroids. All corneal grafts remained clear throughout the follow up. Conclusions-In this study it was shown that MMF is just as eVective as CSA in preventing acute rejection following high risk corneal transplantation. Mycophenolate mofetil represents a promising alternative therapeutic option in patients who are at high risk for corneal graft failure.

Systemic immunosuppression with MMF over 6 months is relatively well tolerated and improves rejection-free graft survival following high-risk keratoplasty statistically significant, even in the long run.

Summary The purpose of this study was to evaluate for the first time the efficacy and safety of topical FK506 in patients undergoing penetrating normal‐risk keratoplasty in a prospectively randomized clinical trial. Twenty patients were treated with FK506 0.06% three times per day for 6 months postoperatively. An additional 20 patients received five drops of prednisolone acetate 1% tapered within 6 months. All patients received 1 mg/kg bodyweight/day of systemic fluocortolon tapered within 3 weeks postoperatively. Clear graft survival, ratio of immune reactions and side effects were the main outcome measures. One year postoperatively all patients of the FK 506 group were free from immune reactions, in contrast to 84% in the steroid group (Kaplan–Meier values; P = 0.9 in the log rank test). None of the patients developed irreversible graft failure so far. In eight patients of the FK506 group premature withdrawal of the drug was deemed appropriate because of local side effects. FK506 might turn out to become an effective immunoprophylaxis in subjects undergoing penetrating normal‐risk keratoplasty. Local discomfort should be further reduced.