Biology and medicine on ocular surface restoration: Advancements and limits of limbal stem cell deficiency treatments

Ocular vision can be hampered by corneal damages, sensibly reducing patients' quality of life and having important social and economic consequences. Ocular surface diseases, which often lead to corneal opacities with visual impairment are the most severe forms of the Limbal Stem Cell Deficiency (LSCD). The present review provides an updated perspective on the available treatments for LSCD, focusing on clinical and biological features, as well as critical points to monitor during clinical translation. Recently developed surgical treatments for LSCD are described, along with their benefits and limitations, with the aim of addressing the issue of correct patient selection. Autologous surgical approaches have been attempted, such as conjunctival limbal autograft (CLAD), simple limbal epithelial transplantation (SLET), and others. Allogeneic limbal stem cell transplantation represents an alternative but carries risk of rejection and requires immunosuppression. Other potential treatments are based on induced pluripotent stem cells (iPSCs), but they require further investigation. The development of advanced therapy medicinal products (ATMPs) such as cultivated limbal epithelial transplantation (CLET), or the use of other epithelia as cultivated oral mucosal epithelial cell transplantation (COMET), has opened additional therapeutic possibilities. Some common critical issues in clinical translation are described, such as patient selection, biopsy procurement, or the use of human/animal derived components, which require rigorous validation to ensure safety and efficacy. Personalized medicine is a promising field for ocular surface restoration, where longterm follow-up studies and standardized criteria are crucial to evaluate the efficacy of these treatments and their cost-effectiveness in providing high-value healthcare.