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 option 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 rejection, was examined in a rat model.


METHODS
All AO (strain) recipients of PVG grafts were assigned to the following treatment groups: Group 1 (controls), 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 allografts were clinically evaluated and blood CsA levels were measured at various time points.


RESULTS
Untreated controls rejected their allografts after 13 days. Regression analysis showed a strongly significant positive correlation between graft survival time and duration of cyclosporine therapy. There 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 postoperative treatment had no advantage over a solely postoperative treatment regimen. The moment of rejection was characterized by a low to undetectable CsA concentration.


CONCLUSIONS
The present study demonstrates a significant influence 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 biological evidence of the mechanism of action of CsA on the efferent arm of graft rejection.
Claerhout
I
I
Department of Ophthalmology, Ghent University Hospital, De Pintelaan 185, 9000 Gent, Belgium. ilse.claerhout@rug.ac.be
Beele
H
H
Verstraete
A
A
Van den Broecke
C
C
Kestelyn
P
P
D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D016039:Corneal Transplantation; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine