Prevention of high risk corneal graft rejection using cyclosporine A (CsA) incorporated into a collagen matrix

The aim of this work was to compare the efficacy of cyclosporine (CsA) collagen shields and fragments in suppressing experimental allograft rejection in an animal model for high risk keratoplasty. Altogether 23 experimental animals were treated either with plain collagen shields, oral cyclosporine, collagen CsA shields, or with CsA collagen fragments after corneal transplantation (PKP) in previously vascularized corneas. The study medications were started immediately following PKP. For these animals slit lamp examinations were performed twice a week for the duration of the experiment and the signs of corneal rejection were observed. The animals were followed until an irreversible rejection or until the end of the experiment (14-149 days). The inflammation of the graft was also evaluated histologically when animals were sacrificed. The grafts treated with plain collagen shields all were rejected within 36 days, and the mean graft survival time for these corneas was 25 days. Five transplants that were treated with oral CsA had better survival, and two of five grafts stayed clear until postoperative day 119, when the treatment was stopped. The best graft survival was seen in grafts treated with CsA collagen fragments and all these stayed clear up to 77 days postoperatively. The treatment of the grafts with CsA collagen shields was almost as effective as with CsA fragments, and first signs of rejection appeared as late as nine weeks postoperatively in two of seven grafts. The other of these rejected corneas were later treated with CsA collagen fragments and showed a dramatic improvement in transparency of the cornea and disappearance of inflammation of the graft. The discontinuation of study medication caused an irreversible rejection to appear in a previously clear graft that had been treated successfully with any study medication. We conclude that topical CsA in shields or in fragments will provide a significant advance over systemic CsA alone, and that CsA fragments appear to be as effective as shields in preventing corneal allograft rejection.