Injectable corneal endothelial cell therapy: recent progress, translational barriers, and future directions

Introduction Corneal endothelial dysfunction, most commonly caused by Fuchs endothelial corneal dystrophy (FECD) or pseudophakic bullous keratopathy (PBK), leads to stromal edema and corneal decompensation when endothelial cell density (ECD) falls below 500–700cells/mm². Standard treatment via corneal transplantation, including Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK), is limited by the need to standardize corneal endothelial cell culture, donor shortages, immune rejection, and technical complications. This review aims to summarize recent advances in injectable corneal endothelial cell (CEC) therapy, critically appraise translational challenges, and discuss future directions for establishing this regenerative approach as a global treatment. Design Narrative review of pre-clinical and clinical studies examining CEC injection therapy. Methods Relevant literature was analyzed to evaluate innovations in Human corneal endothelial cells (HCEC) preparation, culture techniques, delivery methods, and strategies to enhance cell adhesion and survival. Studies reporting preclinical models and human clinical trials were included to assess safety, efficacy, and translational feasibility. Results Corneal endothelial cells (CEC) injections have achieved significant advancement since their development. Simple cultured CEC injections showed poor efficacy due to limited cell adhesion and survival, but the introduction of ROCK inhibitors along with cultured CECs demonstrated improvement in corneal transparency up to 5 years. Advancements in cell delivery techniques like hydrogel, carrier-assisted injections, magnetically guided injections, as well as alternative cell sources have shown promising results in pre-clinical studies, but human studies are still ongoing. Despite advancements, persisting challenges include phenotypic stability, and longterm safety and efficacy. Discussion Injectable CEC therapy is a promising minimally invasive alternative to corneal transplantation. While early clinical outcomes are encouraging, further work is required to optimize cell preparation, delivery, and long-term safety, and to establish the therapy as a scalable, globally applicable treatment for endothelial failure.