Reframing Technology and Ethics in Corneal Xenotransplantation: A Scoping Review of Standards and Safety in Ophthalmology

ABSTRACT Xenotransplantation offers a potential solution to the critical global organ shortage by allowing the transplantation of organs from non‐primate animals to humans. To address the critical barriers of biological safety, zoonotic infections, and immunological rejection, this review evaluates current innovations in genetically engineered donor species strategies and assesses existing ophthalmological standards, employing specific expression of human regulatory proteins (hCD46/hCD55) and genetically modified triple knockout ( GGTA1 / B4GalNT2 / CMAH ), biophysical thresholds, porcine cytomegalovirus screening, bacterial/mycotic cultures, and DNA sequencing for unidentified organisms. Employing a snowball strategy across PubMed Central, ResearchGate, and Wiley Online Library, 47 articles were selected and reported following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses Extension for Scoping Reviews. The feasibility of xenotransplantation relies heavily on advancements in donor technology and genotype transparency, animal husbandry and biosafety, infectious testing and surveillance, recipient monitoring and lifetime surveillance, biosafety incident and response plan, data governance, sharing and oversight, and animal welfare and social license, necessitating pathogen observation, biosecure storage, bioexclusion monitoring, and good manufacturing practice‐style manual, quantitative polymerase chain reaction for porcine cytomegalovirus, porcine reproductive and respiratory syndrome virus, hepatitis E virus, alongside porcine endogenous retrovirus‐A/B/C; metagenomic sequencing initially, followed by 1, 3, 6, and 12 months, and subsequently once every year, systematic and preliminary persistent sampling evaluations, independent data safety monitoring board, collaborative guidelines, encrypted databases, and data retention. The integration of endothelium‐protective human genes, including hA20 or hHO‐1 , into genetically altered donor corneas in non‐human primate xenografts, is expected to minimize initial post‐transplant endothelial cell density loss by ≥ 20% compared to existing models. While clustered regularly interspaced short palindromic repeats‐based modifications offer transformative potential for xenotransplantation, their reliability currently depends on establishing stringent biosafety standards.