Medical and surgical approaches to prevent corneal graft rejection in high-risk recipients

A substantial number of corneal transplantations are performed in the vascularized and inflamed environments of high-risk recipients, which increases the risk of graft rejection. Managing high-risk keratoplasty is challenging and encompasses numerous pre-, intra-, and post-operative measures. Preoperative measures include treating ocular surface inflammation and corneal neovascularization. Intraoperative measures mainly involve performing lamellar keratoplasty, if possible, to reduce the loads of alloantigens introduced to the recipient's immune system. The key step in the prevention of immunologic rejection in high-risk recipients is the administration of topical and systemic immunosuppressive medications for a long term. Topical corticosteroids are frequently administered after corneal transplantation; however, they are insufficient to prevent graft rejection following high-risk keratoplasty. In such cases, various systemic immunosuppressive medications can be employed with inconstant success rates. Nonetheless, these agents can result in potentially serious and sometimes life-threatening adverse reactions. Furthermore, the ideal method of administration, dosage, frequency, and duration of application of these medications have not been identified for individual cases of high-risk keratoplasty. New strategies, including targeted biological treatments and tolerance-inducing protocols, may hold promise in decreasing the risk of corneal graft rejection in high-risk settings without the adverse reactions of systemic immunosuppressive treatment.