Rejection and acceptance of corneal allografts

Corneal transplantation is successful in the short-term, but the long-term prognosis has not improved over the past 20 years. Here, we review recent findings that may contribute to improved corneal allograft survival.

A better understanding of the molecular pathways affecting corneal graft survival has led to more targeted approaches to immune modulation. Costimulatory molecule blockade, inhibition of chemokine-chemokine receptor interactions, modulation of apoptotic pathways, and reduction of corneal neovascularization and lymphangiogenesis have been shown to prolong corneal graft survival in animal models. Conventional immunosuppressive drugs have been tested in new combinations and formulations with some success. Two randomized prospective clinical trials in clinical penetrating corneal transplantation have been reported, but there remains little evidence on the long-term outcomes of the newer lamellar corneal graft procedures.

New approaches to reducing the impact of rejection on corneal graft survival have focussed on topical rather than systemic therapies, and on component corneal transplantation. The most successful experimental strategies have been those in which more than one pathway has been targeted; it now seems likely that to improve clinical allograft survival, simultaneous modulation of multiple axes of the rejection process will be necessary.