Allogeneic whole-eye transplantation: advancements, challenges, and future directions in vision restoration.

Vision loss remains a significant global health burden, primarily driven by irreversible ocular conditions such as age-related macular degeneration (AMD), glaucoma, severe ocular trauma, and intraocular malignancies. Despite advances in retinal prosthetics and stem cell-based therapies, current treatment options are still limited in their ability to fully restore visual function. Allogeneic whole-eye transplantation (WET) has recently gained attention as a novel and potentially transformative strategy for vision restoration. This review synthesizes recent progress in the field, including advancements in microsurgical techniques, immunosuppressive protocols, and neural integration strategies, drawing on evidence from both preclinical animal models and emerging human studies. Key components, including optic nerve (ON) regeneration, vascular anastomosis, immune tolerance, and donor-recipient matching, are critically examined. Furthermore, we address ongoing barriers, including graft viability, chronic rejection, central visual pathway rewiring, and ethical considerations surrounding the procurement of donor eyes. While substantial milestones have been achieved, particularly in experimental settings, clinical translation remains in its early stages. This review highlights current limitations and proposes future directions for multidisciplinary research aimed at overcoming these challenges and advancing WET toward clinical reality.