Cultivated Oral Mucosal Epithelial Transplantation for Limbal Stem Cell Deficiency: A Scoping Review of Indications, Platforms, Outcomes and Safety

Abstract

Background: Cultivated oral mucosal epithelial transplantation (COMET/CAOMECS) is an autologous, immunosuppression-sparing option for ocular surface reconstruction in limbal stem cell deficiency (LSCD). After two decades, indications, platforms and outcome definitions vary, and COMET�s position relative to limbal-derived epithelium remains uncertain. Methods: We conducted a PRISMA-ScR scoping review of human clinical studies (PubMed, 2000�30 December 2025) with hand-searching and regulatory sources. Eligible reports included COMET/CAOMECS series and comparative cohorts (CLET/ACLET, SLET, KLAL/CLAL). The primary outcome was anatomical success (stable epithelialised cornea without recurrent persistent epithelial defect, progressive conjunctivalisation or uncontrolled neovascularisation at last assessment). Given heterogeneity in definitions and analytic frames (fixed-time vs. Kaplan�Meier [KM]), results were synthesised narratively by indication and platform. Results: Twenty-five reports (893 eyes; 821 patients) were included. Aetiologies were predominantly burns and SJS/TEN. Across amniotic membrane-based mixed-aetiology series, 12-month anatomical success clustered around 55�70%. Aggregated descriptively across COMET eyes, 211/467 (45%) had a stable surface at last follow-up. Epithelialisation was generally rapid in quiet AM-based reconstructions and slower with severe adnexal disease or carrier-free platforms. Mean BCVA improved from 1.8 � 0.7 to 1.4 � 0.7 logMAR (471 eyes); ?2-line gains occurred in 308/471 (65.4%). A matched comparison suggested better 12-month survival, less neovascularisation and better BCVA with substrate-free versus AM-carried COMET; a biomaterial-/feeder-free platform reconstructed most eyes but failed more often with four-quadrant symblepharon. Observational comparative cohorts suggested higher surface survival and average visual gain with limbal-derived epithelium, at the cost of systemic immunosuppression. Conclusions: In appropriately selected bilateral LSCD, COMET offers immunosuppression-sparing reconstruction with moderate, durable surface stability and clinically meaningful visual gains when performed on a quiet, optimised surface. Platform refinements�particularly substrate-free constructs�and prospective, indication-defined comparative studies with harmonised outcomes are needed to define COMET�s role relative to limbal-derived epithelium.