Nonsurgical Therapies for Preventing Corneal Scarring: A Systematic Review of the Past Decade

Corneal scarring remains a leading cause of visual impairment and preventable blindness worldwide, particularly where access to corneal transplantation is limited. Over the past decade, significant advances have been made in nonsurgical therapies aimed at preventing or mitigating corneal fibrosis. This systematic review summarizes emerging nonsurgical interventions, including synthetic drugs, plant- and animal-derived bioactives, biologics, cell-based therapies, and gene therapies. A paradigm shift has occurred from nonspecific anti-inflammatory agents toward therapies targeting fibrotic-related pathways (e.g., transforming growth factor-β, Rho-associated protein kinase, extracellular matrix remodeling), with growing emphasis on regenerative strategies such as exosome treatments and gene modulation. Despite promising preclinical data, major translational challenges remain, including delivery optimization, scalability, and regulatory hurdles. Standardizing outcome measures across models and exploring combination therapies targeting multiple fibrotic pathways represent critical future directions. Continued research to validate the efficacy and safety of these emerging interventions is essential to expand therapeutic options and enhance vision restoration efforts globally.