Regenerating the Ocular Surface: Emerging Therapies and Innovations in Limbal Stem Cell Deficiency

Abstract

Limbal stem cell deficiency (LSCD) is a debilitating ocular surface disorder resulting from the loss or dysfunction of limbal epithelial stem cells (LESCs) that are essential for maintaining corneal transparency and integrity. The condition can lead to chronic inflammation, corneal neovascularization, conjunctivalization, and significant visual impairment. This review aims to provide a comprehensive overview of the pathophysiology, diagnostic approaches, and current management strategies for LSCD, with a particular emphasis on emerging stem cell-based therapies and regenerative techniques. It also highlights current challenges and future therapeutic directions in LSCD management. Recent advances have significantly improved our understanding of LSCD and expanded available therapeutic options, particularly in the realm of stem cell transplantation. Techniques such as simple limbal epithelial transplantation (SLET), cultivated limbal epithelial transplantation (CLET), and alternative sources like oral mucosal and induced pluripotent stem cells (iPSCs) have shown promising outcomes. Diagnostic modalities such as in vivo confocal microscopy (IVCM) and impression cytology are useful adjuncts for early and accurate diagnosis. The management of LSCD has evolved from purely symptomatic treatment to targeted regenerative approaches aimed at restoring the ocular surface. While several innovative therapies are under clinical investigation, challenges such as donor limitations, immunologic rejection, and regulatory hurdles persist. Continued advances in regenerative medicine and translational research may improve long-term ocular surface restoration and visual outcomes in patients with LSCD.