First-in-human Porcine-to-human Corneal Endothelial Xenotransplantation for Bullous Keratopathy

BACKGROUND: Corneal blindness remains a major cause of preventable vision loss worldwide; however, the global shortage of donor corneas severely limits transplantation. Xenotransplantation using porcine corneas represents a potential solution. Here, we report the first-in-human transplantation of porcine corneal endothelial grafts. METHODS: Descemet's stripping automated endothelial keratoplasty (DSAEK) was performed using pathogen-free, nongenetically modified porcine grafts in 2 patients with painful bullous keratopathy and irreversible vision loss. One patient received topical corticosteroids alone, the other systemic mycophenolate mofetil. Clinical outcomes, graft survival, immune rejection, and zoonotic safety were monitored over extended follow-up. RESULTS: Both grafts adhered well and restored early corneal clarity. Immune rejection occurred on days 41 and 154, with longer graft survival in the patient under systemic immunosuppression. Histologic and immunohistochemical revealed chronic inflammatory infiltration with lymphocytes and eosinophils, together with lymphocytes, eosinophils, complement, immunoglobulins, T cells, B cells, and macrophages. No zoonotic transmission was detected over 34 mo. Both patients subsequently underwent successful allogeneic corneal transplantation, resolving ocular pain. CONCLUSIONS: Porcine corneal endothelial grafts can temporarily restore corneal transparency and relieve symptoms in end-stage bullous keratopathy; however, immune rejection remains the principal barrier to durable survival. Absence of zoonotic infection supports initial clinical safety.