Abstract
Limbal stem cell deficiency (LSCD) is a severe ocular surface disorder that remains a major therapeutic challenge, particularly in bilateral disease where autologous limbal tissue is unavailable. Over the past three decades, stem cell-based interventions have transformed LSCD management, evolving from large limbal grafts to refined ex vivo expansion techniques and alternative stem cell sources. Despite these advances, long-term clinical outcomes remain variable and are strongly influenced by disease severity, immune rejection, stem cell quality, and optimization of the ocular surface microenvironment. This report examines the current landscape of surgical and stem cell-based therapies for LSCD, including autologous and allogeneic limbal epithelial transplantation, simple limbal epithelial transplantation, oral mucosa-derived approaches, mesenchymal stem cell therapies, and emerging induced pluripotent stem cell-derived corneal epithelium. We highlight key clinical outcomes, biological limitations, and translational challenges. Finally, we discuss future directions required to improve therapeutic efficacy and accessibility, including improved stem cell characterization and the development of hypoimmune or universal donor cell products.