Mycophenolate mofetil (MMF) following penetrating high-risk keratoplasty: long-term results of a prospective, randomised, multicentre study.

BACKGROUND: The purpose of this prospective, randomised, multicentre study was to prove the efficacy and safety of mycophenolate mofetil (MMF) in preventing graft rejection and in improving clear graft survival following high-risk keratoplasty. METHODS: In all, 98 of 140 scheduled patients were included in this study (57 MMF, 41 control). Recruitment was stopped prematurely due to a statistically significant result. The patients in the MMF group received MMF orally 2 x 1 g daily for 6 months. All of the patients received fluocortolone 1 mg/kg/day tapered over 3 weeks and topical prednisolone acetate 5 x /day tapered over 5 months. Main criteria were immune reaction-free and clear graft survival, and the occurrence of side effects. RESULTS: The mean follow-up time was 34.9+/-16.3 (mean+/-SD) months. Eleven patients withdrew from the study (nine patients due to protocol deviation, two because of side effects). Six reversible and two irreversible graft rejections occurred in the MMF group, and five reversible and seven irreversible rejections in the control group. The Kaplan-Meier analysis revealed an immune reaction-free graft survival after the mean follow-up time of 83% in the MMF group and 64.5% in the control group (P=0.044). Graft failure occurred in 10 MMF-treated patients (two due to rejection) and in nine patients in the control group (seven due to rejection). A total of 36 of 57 MMF-treated patients experienced mostly reversible adverse events. CONCLUSIONS: 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.

[Long-term results of FK 506 eye drops following corneal transplantation]. / Langzeitergebnisse mit FK 506-Augentropfen nach Hornhaut-Transplantation.

BACKGROUND: Immunological graft rejection is the main reason for graft failure following corneal transplantation despite the use of topical and systemic steroids. As steroids are associated with side effects, alternative therapeutic strategies are needed. PATIENTS AND METHODS: In this clinical trial patients undergoing corneal transplantation have been prospectively randomised to receive either prednisolone acetate 1 % eye drops 5 x /day, tapering off by one drop every month (n = 20), or to receive FK 506 eye drops 3 x /day for six months (n = 20). Patients in both groups received additionally systemic steroids for three weeks (fluocortolon 1 mg/kg body weight). Primary endpoints were the number of immune reactions and the clear graft survival, the secondary endpoint was the number of side effects. RESULTS: Three immune reactions in the steroid group and one immune reaction in the FK 506 group were seen within the follow-up time of three years. No irreversible graft rejections occurred in either group. Eight patients in the FK 506 group concluded the study early due to local side effects. CONCLUSIONS: In this long-term follow-up the use of FK 506 eye drops following corneal transplantation resulted in a lower number of immune reactions when compared to topical steroids. With a change in the galenic formulation FK 506 might be a powerful therapeutic option for preventing immunological graft rejection.

[Ranking of systemic steroids after normal-risk keratoplasty. Results of a randomized prospective study]. / Stellenwert der systemischen Steroidtherapie nach Normalrisikokeratoplastik. Eine randomisierte prospektive Pilotstudie.

BACKGROUND: The aim of this study was to evaluate the efficacy of sole application of topical steroids after normal-risk keratoplasty. PATIENTS AND METHODS: This randomized prospective clinical study assessed 40 patients who had undergone penetrating normal-risk keratoplasty. Twenty patients were treated exclusively with prednisolone acetate 1% eye drops 5x/day for 6 months postoperatively. Another 20 patients additionally received systemic fluocortolone 1 mg/kg body weight per day tapered within 3 weeks postoperatively. The main outcome measures included clear graft survival, ratio of graft rejection, and side effects. RESULTS: The mean postoperative follow-up was 18+/-9 months. Three graft rejections were observed in the group receiving only topical steroids. Two graft rejections were observed in the group administered combined systemic and topical steroid therapy. None of the patients has developed irreversible graft failure so far. CONCLUSION: Sole topical steroid application seems to be an effective immune prophylaxis in patients undergoing penetrating normal-risk keratoplasty.

Improvement of graft prognosis in penetrating normal-risk keratoplasty by HLA class I and II matching.

BACKGROUND: Owing to contradictory results, HLA matching in penetrating keratoplasty still is equivocal. Different surgical techniques in multicentre studies, missing risk differentiation in high-risk situations, and faulty HLA typing can be identified as main reasons for these contradictory results. In this monocentre study, the value of HLA class I and II matching (A, B, DR loci) was examined in a homogeneous group of 418 normal-risk keratoplasty patients using serological typing techniques for HLA class I and immunogenetic typing techniques for class II. METHODS: Penetrating normal-risk keratoplasty was performed in two groups of patients (group I with 0-2, group II with 3-6 mismatches in the A/B/DR loci). All surgery was carried out by three experienced surgeons according to a standardized scheme. Furthermore, postoperative therapy and controls were standardized. There were no statistically significant differences between the two study groups with regard to the number of ABO or H-Y compatibilities, patient age, patient gender, ratio of previous intraocular surgery, ratio of triple procedures, indication for surgery, follow-up period, donor age, donor gender, post-mortem time of the graft, and endothelial cell density of the graft at the end of organ culture. All HLA typing was performed in a quality-controlled laboratory, serologically for HLA class I (A and B loci) and immunogenetically for HLA class II (DR locus). RESULTS: At 4 years postoperatively, the ratio of clear and rejection-free graft survival was 92% in group I and 66% in group II (Kaplan-Meier estimation, log rank test, P=0.03). Monovariate analysis in the Cox model gave no influence of solitary HLA class I or II matching, but only an influence of combined HLA class I and II matching (P=0.03). CONCLUSIONS: In this monocentre study with proper typing techniques, the beneficial effect of HLA class I plus II matching on clear and rejection-free graft survival could be demonstrated in a homogeneous group of normal-risk keratoplasty patients.