Systemic immunosuppression with mycophenolate mofetil to prevent corneal graft rejection after high-risk penetrating keratoplasty: a 2-year follow-up study

Abstract

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.

Midterm Outcomes of Penetrating Keratoplasty Following Allogeneic Cultivated Limbal Epithelial Transplantation in Patients with Bilateral Limbal Stem Cell Deficiency

“…The rejection rates at 12, 24, and 36 months were 10%, 25%, and 61% in the current study. This was higher than the results of high-risk penetrating keratoplasty in 5 years reported by Chow SP 32 but was lower than that in 2 years reported by Sza ik JP 33 . A failure rate due to graft rejection (25%) was lower than them in the current study.…”

Outcomes of Penetrating Keratoplasty Following Autologous Cultivated Limbal Epithelial Stem Cell Transplantation

“…The Australian Graft Registry reported a rejection rate of 16% in PKP performed for any indication in 2015, although they did not break down the data for high risk PKP . Nonetheless, our rate is lower than that reported for PKP in high risk cases . Our failure rate following rejection is comparable to Basu et al, who reported a 57.7% failure rate after 1 or more episodes of endothelial rejection, although they combined the rejection and failure data for a single‐stage and two‐stage procedures .…”

Third-Party Allogeneic Mesenchymal Stromal Cells Prevent Rejection in a Pre-sensitized High-Risk Model of Corneal Transplantation

“…Firstly, unlike other immunosuppressive drugs such as corticosteroids, it does not alter the expression of MSC immunomodulatory factors ( 42 ) and has been shown to exert a synergistic effect with MSC in a pre-clinical heart transplant model ( 21 ). Secondly, MMF is currently prescribed to patients receiving high-risk cornea transplants including re-grafts ( 43 , 44 ). Our observation that co-administration of MMF did not diminish the anti-rejection of third-party allo-MSC therapy (and trended toward further increase in rejection-free survival) in this high-risk model provides additional evidence of clinical translational potential.…”