Biological extracellular vesicles in tear fluids, such as exosomes, are thought to have physiological functions in the management of healthy ocular surface epithelium, including corneal epithelium. However, the physiological roles of tear extracellular vesicles in the ocular surface remain unclear. In this study, we investigated the physiological function of tear extracellular vesicles in mouse tear fluids in the ocular surface epithelium in vitro. Morphological analysis of the isolated extracellular vesicles from mouse tear fluids was performed using nanoparticle tracking analysis and transmission electron microscopy. The identified particles were characterised by immunoblotting for exosomal markers. After confirming the uptake of tear exosomes in cultured corneal epithelial cells, gene expression changes in mouse cultured corneal epithelial cells after tear exosome treatment were analysed. Immunostaining analysis was performed to confirm cell proliferation in the cultured corneal epithelial cells with tear exosome treatment. Tear fluids from mice contain nanoparticles with exosome-like morphologies, which express the representative exosomal markers CD9 and TSG101. The extracellular vesicles can be taken up by cultivated murine corneal epithelial cells in vitro and induce expression changes in genes related to the cell cycle, cell membranes, microtubules, and signal peptides. Treatment with the tear extracellular vesicles promoted cell proliferation of cultured murine corneal epithelial cells. Our study provides evidence that murine tear fluids contain extracellular vehicles like exosomes and they may contribute to the maintenance of the physiological homeostatic environment of the ocular surface.

This study aimed to report the 3-year clinical outcomes of corneal endothelial keratoplasty (EK) in late-stage elderly patients (≥75 years) compared with younger patients (<75 years). Retrospective observational study. Patients who underwent EK, including Descemet’s stripping automated keratoplasty (DSAEK) and non-Descemet stripping and automated endothelial keratoplasty (nDSAEK) with bullous keratopathy (BK) at Keio University Hospital between 2016 and 2018, were included. Patient characteristics, graft survival rate, best corrected visual acuity (BCVA), corneal endothelial cell density (ECD), and complications were compared between the late elderly group (75 years or older) and the younger group (<75 years old) stratified by surgical procedure. Among the 64 eyes and 55 patients who underwent EK, 31 eyes and 30 patients were in the late elderly group (81.4±3.7 years), and 33 eyes and 25 patients were in the younger group (66.2±9.1 years). There was no difference between the groups in terms of the cause of BK, and PBK was more common in the DSAEK group in the late elderly group (p = 0.029). There was no difference in graft survival between the two groups during the follow-up period. In the late elderly group, graft survival was significantly better in the nDSAEK group than in the DSAEK group (p = 0.045). BCVA and postoperative ECD improved in both groups. There were no differences in intraoperative or postoperative complications between the late elderly and younger groups. EK for BK in late elderly patients resulted in postoperative visual improvement, with similar efficacy and safety to those of EK for BK in younger patients.

Background/Objectives: To characterize the early clinical manifestations and treatment outcomes of Japanese patients with Norrie disease. Retrospective multicenter observational case series with a systematic literature review. Methods: Fourteen infants with genetically confirmed Norrie disease were retrospectively reviewed. Clinical findings, disease stage, interocular asymmetry, treatment, and visual outcomes were evaluated using a modified staging system based on familial exudative vitreoretinopathy (FEVR) and the International Classification of Retinopathy of Prematurity. A systematic review of previously reported Japanese cases was performed to assess disease severity at initial diagnosis. Results: Twenty-eight eyes of 14 patients were included. The median age at the initial examination was 2.5 months. Twenty-three eyes (82%) had stage 5 retinal detachment, whereas only five eyes (18%) had stage 2 or 4 disease. Interocular asymmetry was uncommon. Twenty-one eyes (75%) underwent laser photocoagulation and/or surgery. Visual outcomes were poor; at the most recent follow-up, all but two stage 4 eyes treated with laser photocoagulation had no light perception. Combined analysis of our cohort and the literature review identified 29 Japanese patients from 19 families and demonstrated that most already had advanced bilateral retinal detachment within the first two months of life. Conclusions: Norrie disease typically presents with advanced bilateral retinal detachment during early infancy, leaving limited opportunities for effective intervention. Early recognition and genetic diagnosis are therefore essential.

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.