PurposeIn this study, we aimed to evaluate the efficacy and safety of systemic immunosuppression with mycophenolate mofetil (MMF) to prevent corneal graft rejection after high-risk penetrating keratoplasty.MethodsOne hundred and ninety-six consecutive patients who underwent high-risk penetrating keratoplasty defined as the presence of deep vascularization in more than two quadrants, keratouveitis, emergency keratoplasties, and retransplantations were enrolled in the study. Ninety-eight prospectively followed up patients were treated with MMF [with dose adjustment based on mycophenolic acid (MPA) serum concentration], and 98 patients were in the non–MMF-treated retrospectively assessed control group.ResultsDuring a mean of 24 months of observation, immune reactions occurred in eight cases (8 %) and graft rejection with subsequent graft failure occurred in three cases (3 %) in the MMF group. In the control group, graft rejection occurred in 76 cases (78 %) and failure due to graft rejection occurred in 30 cases (31 %). Kaplan–Meier analysis demonstrated that 93 % of the grafts in the MMF-treated group and 47 % in the control group showed no immune rejection (p < 0.01, log-rank test) after a year. Cox regression analysis proved that MMF treatment decreased the risk of graft rejection 11 times (RR = 11, 95.0 % CI 4.8–25, p < 0.0001). Among 98 MMF-treated patients, 13 had gastric discomfort, three developed leucopenia, and two had anemia that resolved after MMF dose reduction.ConclusionsMMF treatment after high risk penetrating keratoplasty is safe and reduces the incidence of immune graft rejection and graft failure. Side effects were rare and reversible in all but one case.

The first human corneal transplantation was performed in 1905 by Eduard Zirm in the Olomouc Eye Clinic, now Czech Republic. However, despite great advancements in microsurgical eye procedures, penetrating keratoplasty in high-risk patients (e.g., vascularized or inflamed corneal tissue, consecutive transplants) remains a challenge. The difficulty is mainly due to the risk of irreversible allograft rejection, as an ocular immune privilege in these patients is abolished and graft rejection is the main cause of corneal graft failure. Therefore, tailored immunosuppressive treatment based on immunological monitoring [e.g., donor-specific antibodies (DSA)] is considered one of the best strategies to prevent rejection in transplant recipients. Although there is indirect evidence on the mechanisms underlying antibody-mediated rejection, the impact of DSA on cornea transplantation remains unknown. Determining the role of pre-existing and/or de novo DSA could advance our understanding of corneal graft rejection mechanisms. This may help stratify the immunological risk of rejection, ultimately leading to personalized treatment for this group of transplant recipients.

Purpose In this study, we aimed to evaluate the efficacy and safety of systemic immunosuppression with mycophenolate mofetil (MMF) to prevent corneal graft rejection after highrisk penetrating keratoplasty. Methods One hundred and ninety-six consecutive patients who underwent high-risk penetrating keratoplasty defined as the presence of deep vascularization in more than two quadrants, keratouveitis, emergency keratoplasties, and retransplantations were enrolled in the study. Ninety-eight prospectively followed up patients were treated with MMF [with dose adjustment based on mycophenolic acid (MPA) serum concentration], and 98 patients were in the non-MMF-treated retrospectively assessed control group. Results During a mean of 24 months of observation, immune reactions occurred in eight cases (8 %) and graft rejection with subsequent graft failure occurred in three cases (3 %) in the MMF group. In the control group, graft rejection occurred in 76 cases (78 %) and failure due to graft rejection occurred in 30 cases (31 %). Kaplan-Meier analysis demonstrated that 93 % of the grafts in the MMF-treated group and 47 % in the control group showed no immune rejection (p<0.01, log-rank test) after a year. Cox regression analysis proved that MMF treatment decreased the risk of graft rejection 11 times (RR=11, 95.0 % CI 4.8-25, p<0.0001). Among 98 MMFtreated patients, 13 had gastric discomfort, three developed leucopenia, and two had anemia that resolved after MMF dose reduction. Conclusions MMF treatment after high risk penetrating keratoplasty is safe and reduces the incidence of immune graft rejection and graft failure. Side effects were rare and reversible in all but one case.

Purpose In this study, we aimed to evaluate the efficacy and safety of systemic immunosuppression with mycophenolate mofetil (MMF) to prevent corneal graft rejection after highrisk penetrating keratoplasty. Methods One hundred and ninety-six consecutive patients who underwent high-risk penetrating keratoplasty defined as the presence of deep vascularization in more than two quadrants, keratouveitis, emergency keratoplasties, and retransplantations were enrolled in the study. Ninety-eight prospectively followed up patients were treated with MMF [with dose adjustment based on mycophenolic acid (MPA) serum concentration], and 98 patients were in the non-MMF-treated retrospectively assessed control group. Results During a mean of 24 months of observation, immune reactions occurred in eight cases (8 %) and graft rejection with subsequent graft failure occurred in three cases (3 %) in the MMF group. In the control group, graft rejection occurred in 76 cases (78 %) and failure due to graft rejection occurred in 30 cases (31 %). Kaplan-Meier analysis demonstrated that 93 % of the grafts in the MMF-treated group and 47 % in the control group showed no immune rejection (p<0.01, log-rank test) after a year. Cox regression analysis proved that MMF treatment decreased the risk of graft rejection 11 times (RR=11, 95.0 % CI 4.8-25, p<0.0001). Among 98 MMFtreated patients, 13 had gastric discomfort, three developed leucopenia, and two had anemia that resolved after MMF dose reduction. Conclusions MMF treatment after high risk penetrating keratoplasty is safe and reduces the incidence of immune graft rejection and graft failure. Side effects were rare and reversible in all but one case.