Exosomes, nanosized extracellular vesicles of 30–150 nm, are shed by almost all cell types. Bearing proteins, lipids, RNAs, and DNAs, exosomes have emerged as vital biological mediators in cell-to-cell communication, affecting a plethora of physiological and pathological processes. Particularly, mounting evidence indicates that immunologically active exosomes can regulate both innate and adaptive immune responses. Herein, we review recent advances in the research of exosomes in several immune-mediated eye diseases, including Sjögren’s syndrome (SS) dry eye, corneal allograft rejection, autoimmune uveitis, and age-related macular degeneration (AMD). Additionally, we discuss the potential of exosomes as novel biomarkers and drug delivery vesicles for the diagnosis and treatment of eye diseases.

Introduction The purpose of this study was to explore the effects of repeated low-level red-light (RLRL) therapy on the structure and vasculature of the choroid and retina in Chinese children with premyopia. Methods This study was a single-center randomized clinical trial. A total of 94 children with premyopia (− 0.50 D < spherical equivalent [SE] ≤ + 0.75 D) were randomly assigned to either the RLRL therapy or control group. Follow-up visits were planned at 1, 3, 6, 9, and 12 months. Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Choroidal thickness (CT), retinal thickness (RT), superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), choriocapillaris perfusion area (CCPA), and choroidal vessel volume (CVV) were measured by optical coherence tomography angiography, centered on the foveal, parafoveal (ParaF), and perifoveal (PeriF) regions. Results The thickening of the choroid was observed across the entire macular region at different time points in the RLRL therapy group. Relative to the baseline measurement, foveal CT significantly increased at the 1-month follow-up with RLRL therapy, with a mean (± standard deviation [SD]) adjusted change of 16.96 ± 19.87 μm. The greatest magnitude of foveal CT changes was observed at the 3-month visit (an increase of 19.58 ± 20.59 μm), with a slight reduction in the extent of foveal CT increase at the 6-month visit (an increase of 15.85 ± 23.77 μm). The second greatest CT increase was observed at the 9-month visit (an increase of 19.57 ± 35.51 μm), after which the extent of CT increase gradually decreased until the end of the study at the 12-month visit (an increase of 11.99 ± 32.66 μm). We also observed a significant increase in CT in the ParaF and PeriF areas in the RLRL group over 12 months. In contrast, CT across the entire macular region in the control group significantly decreased throughout the follow-up visits (all P < 0.05). Regarding the vascular parameters of the choroid, significant increases in CVV were observed primarily in the ParaF and PeriF regions of the choroid in the RLRL group. In comparison, the control group exhibited decreases in CVV throughout the entire area. Furthermore, notable elevations in CCPA were detected in the PeriF area of the choroid in the RLRL group during the 1-month (an increase of 0.40 mm²), 3-month (an increase of 0.25 mm²), and 12-month visits (an increase of 0.42 mm²) (all P < 0.05). In addition, no notable differences were observed between the groups regarding foveal RT and retinal vascular parameters throughout the 12 months (P > 0.05). Notably, RLRL therapy achieved a notable reduction in SE shift by 73.8%, a substantial decrease in AL change by 67.9%, and a significant reduction in myopia incidence by 45.1% within 1 year. Conclusion Our study demonstrated a significant increase in CT and flow in the RLRL-treated eyes throughout the 12-months of the study. Combined with its reduction in spherical equivalent progression and axial elongation, RLRL could be used as an effective therapy for preventing progression in premyopes. Trial Registration ChiCTR2200062028.

Background/aims To compare the effects of repeated low-level red light (RLRL) treatment on axial length growth and refractive error changes in myopic and premyopic children. Methods Subjects were assigned randomly to four subgroups: myopia-RLRL group (M-RL), myopia-control group (M-C), premyopia-RLRL group (PM-RL) and premyopia-control group (PM-C). Subjects in the RLRL group completed a 12-month treatment composed of a 3 min RLRL treatment session twice daily, with an interval of at least 4 hours, for 7 days per week. Visits were scheduled before and at 1-month, 3-month, 6-month, 9-month and 12-month follow-up after the treatment. Repeated-measures analysis of variance was used to compare the spherical equivalent refractive errors (SE) and axial length (AL) changes between the groups across the treatment period. Results After 12 months of treatment, in the myopia group, SE and AL changes were −0.078±0.375 D and 0.033±0.123 mm for M-RL and −0.861±0.556 D and 0.415±0.171 mm for M-C; in the premyopia group, the progression of SE and AL was −0.181±0.417 D and 0.145±0.175 mm for PM-RL and −0.521±0.436 D and 0.292±0.128 mm for PM-C. PM-RL indicated a lower myopia incidence than PM-C (2.5% vs 19.4%). Additionally, the percentage of AL shortening in the M-RL was higher than that in the PM-RL before the 9-month follow-up. Conclusion RLRL effectively delayed myopia progression in children with myopia and reduced the incidence of myopia in premyopic children. Moreover, RLRL exhibited a stronger impact on myopic children compared with premyopic individuals.

Purpose. This study aims to evaluate dry eye and ocular surface conditions of myopic teenagers by using questionnaire and clinical examinations.Methods. A total of 496 eyes from 248 myopic teenagers (7–18 years old) were studied. We administered Ocular Surface Disease Index (OSDI) questionnaire, slit-lamp examination, and Keratograph 5M. The patients were divided into 2 groups based on OSDI dry eye standard, and their ocular surfaces and meibomian gland conditions were evaluated.Results. The tear meniscus heights of the dry eye and normal groups were in normal range. Corneal fluorescein scores were significantly higher whereas noninvasive break-up time was dramatically shorter in the dry eye group than in the normal group. All three meibomian gland dysfunction parameters (i.e., meibomian gland orifice scores, meibomian gland secretion scores, and meibomian gland dropout scores) of the dry eye group were significantly higher than those of the normal group (P<0.0001).Conclusions. The prevalence of dry eye in myopic teenagers is 18.95%. Meibomian gland dysfunction plays an important role in dry eye in myopic teenagers. The Keratograph 5M appears to provide an effective noninvasive method for assessing ocular surface situation of myopic teenagers.

Background: Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been increasingly proved as promising immunomodulators against some autoimmune disorders. However, the possible effect and the underlying mechanism of MSC-sEVs in autoimmune dry eye have been rarely studied.Methods: Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUC-MSC-sEVs) were subconjunctivally injected to rabbit dry eye model, and their preventive or therapeutical effects were assessed by recording the clinical and histological scores. Quantitative real-time PCR (Q-PCR), western blot and flow cytometry were performed to evaluate the immunomodulatory effects of hUC-MSC-sEVs on macrophages and T regulatory cells (Tregs) both in vivo and in vitro, and the in vitro T cell proliferation was detected by Bromodeoxyuridine (BrdU) assay. In addition, high expression of miR-100-5p in hUC-MSC-sEVs was identified by Q-PCR, and the functional role of sEVs-miR-100-5p on macrophages was explored by a series of co-culture experiments using sEVs derived from hUC-MSCs transfected with miR-100-5p inhibitor.Results: We firstly demonstrated that hUC-MSC-sEVs had the preventive and therapeutical effects on rabbit autoimmune dacryoadenitis, an animal model of Sjögren’s syndrome (SS) dry eye. Further investigation revealed that hUC-MSC-sEVs administration effectively elicited macrophages into an anti-inflammatory M2 phenotype and elevated the proportion of Tregs both in vivo and in vitro, which contributed to reduced inflammation and improved tissue damage. Importantly, hUC-MSC-sEVs-educated macrophages with M2-like phenotype exhibited strong capacity to inhibit CD4+ T cell proliferation and promote Treg generation in vitro. Mechanistically, miR-100-5p was highly enriched in hUC-MSC-sEVs, and knockdown of miR-100-5p in hUC-MSC-sEVs partially blunted the promotion of hUC-MSC-sEVs on M2 macrophage polarization and even attenuated the effect of hUC-MSC-sEVs-educated macrophages on T cell suppression and Treg expansion.Conclusion: Our data indicated that hUC-MSC-sEVs alleviated autoimmune dacryoadenitis by promoting M2 macrophage polarization and Treg generation possibly through shuttling miR-100-5p. This study sheds new light on the application of MSC-sEVs as a promising therapeutic method for SS dry eye.