The effect of duration and timing of systemic cyclosporine therapy on corneal allograft survival in a rat model

Background: Systemic cyclosporine A (CsA) remains a valuable treatment opti on in the prevention of corneal graft rejection, but the question of timing and duration of this systemic therapy remains unresolved. The effect of a pre- and postoperative dosing schedule, related to the expected moment of r ejection, was examined in a rat model. Methods: All AO (strain) recipients of PVG grafts were assigned to the following treatment groups: Group 1 (con trols), groups 2-5 (a postoperative treatment regimen of CsA for 5, 10, 15 and 30 days respectively) and groups 6 and 7 (CsA preoperatively for 5 days and postoperatively for another 5 or 10 days respectively). Corneal allogr afts were clinically evaluated and blood CsA levels were measured at variou s time points. Results: Untreated controls rejected their allografts after 13 days. Regression analysis showed a strongly significant positive correla tion between graft survival time and duration of cyclosporine therapy. Ther e was no difference in graft survival between groups 3 (CsA 10 days) and 4 (CsA 15 days). A pre-operative dosing schedule of CsA followed by postopera tive treatment had no advantage over a solely postoperative treatment regim en. The moment of rejection was characterized by a low to undetectable CsA concentration. Conclusion: The present study demonstrates a significant inf luence of the duration of systemic CsA administration on allograft survival time. However, preoperative administration of CsA does not seem to have an additional influence on graft survival, which is in line with the biologic al evidence of the mechanism of action of CsA on the efferent arm of graft rejection.