Extracellular Vesicles in Ocular Surface and Anterior Segment Medicine: Biological Roles, Therapeutic Applications, and Diagnostic Potential

Extracellular vesicles (EVs) are increasingly recognized as mediators of intercellular communication and as potential therapeutic and diagnostic platforms. In the ocular surface and anterior segment, EVs are released by epithelial, stromal, endothelial, immune, and aqueous outflow-related cells and are also detectable in tears and aqueous humor. Experimental studies suggest that EVs may promote corneal epithelial repair, modulate local immune responses, reduce stromal fibrosis, and participate in extracellular matrix regulation within the trabecular meshwork. In parallel, mesenchymal stromal cell-derived EVs are being investigated as cell-free therapeutics, while engineered EVs and EV–lipid hybrid systems may facilitate the delivery of nucleic acids and other therapeutic cargo to anterior segment tissues. Tear- and aqueous humor-derived EV preparations have also yielded candidate molecular signatures for ocular surface disease, glaucoma, and selected systemic disorders. However, much of the current evidence remains preclinical or exploratory. Reported effects are frequently based on conditioned medium, EV-enriched fractions, or incompletely characterized preparations, making it difficult to distinguish EV-specific activity from that of the broader secretome. Biomarker studies are additionally limited by small cohorts, low sample volumes, non-vesicular contaminants, and methodological heterogeneity. This review summarizes the biological roles, therapeutic applications, drug-delivery potential, and diagnostic use of EVs in anterior segment medicine. Particular emphasis is placed on the strength of EV-specific evidence, the limitations of extrapolating from non-ocular models, and the methodological, manufacturing, and regulatory requirements for clinical translation. EVs represent a promising interface between anterior segment biology, precision diagnosis, and targeted therapy, but rigorous characterization and comparative validation remain essential.