To assess the effectiveness and safety of repeated low-level red light (RLRL), which is a newly available treatment for myopia control in children and adolescents with high myopia. Multicenter, randomized, parallel-group, single-blind clinical trial (RCT; NCT05184621). Between February 2021 and April 2022, 192 children aged 6 to 16 years were enrolled. Each child had at least one eye with myopia of cycloplegic spherical equivalent refraction (SER) at least -4.0 diopters, astigmatism of 2.0 diopters or less, anisometropia of 3.0 diopters or less, and best-corrected visual acuity of 0.2 logarithm of the minimum angle of resolution or better. Follow-up was completed by April 2023. Participants were randomly assigned at a 1:1 ratio to intervention (RLRL treatment plus single-vision spectacles) or control (single-vision spectacles) groups. The RLRL treatment was administered for 3 minutes per session, twice daily with a minimum interval of 4 hours, 7 days per week. The primary outcome and key secondary outcome were changes in axial length and cycloplegic SER measured at baseline and the 12-month follow-up visit. Participants who had at least 1 post randomization follow-up visit were analyzed for treatment efficacy. Among 192 randomized participants, 188 (97.91%) were included in the analyses (97 in the RLRL group and 95 in the control group). After 12 months, the adjusted mean change in axial length was -0.06 mm (95% confidence interval [CI]: -0.10 to -0.02 mm) and 0.34 mm (95% CI: 0.30 to 0.39 mm) in the intervention and control groups, respectively. There were 48 participants (50.3%) of the intervention group were still experiencing axial shortening more than 0.05mm at 12-month follow-up. Furthermore, the mean spherical equivalent refraction change after 12 months was 0.11 D (95% CI: 0.02 to 0.19 D) and -0.75 D (95% CI: -0.88 to -0.62 D) in the intervention and control groups, respectively. RLRL demonstrates much stronger treatment efficacy among high myopia, with 50.3% experience substantial axial shortening. RLRL provides an excellent solution for the management of high myopia progression, a significant challenge in ophthalmology practice.

Objective: The transparency of the cornea is determined by the extracellular matrix, which is secreted by corneal stromal keratocytes (CSKs). Human-induced pluripotent stem cell (hiPSC)-derived keratocytes (hiPSC-CSKs) can be used in cell-based therapy for treating corneal blindness. Our goal was to develop an effective small molecule-based technique for differentiating hiPSCs into keratocytes. Methods and analysis: hiPSCs were cultured in chemically defined medium, and embryoid bodies (EBs) were generated; these EBs were induced into CSKs using keratocyte-differentiated medium. The expression of keratocyte-specific markers was assessed using quantitative RT-PCR, immunostaining and Western blotting. Results: We found that the expression of genes encoding keratocyte markers, including aldehyde dehydrogenase 1 family member A1 (ALDH1A1), lumican and keratocan, was upregulated. Immunostaining showed positive staining for ALDH1A1 and keratocan in the hiPSC-CSK samples. Similarly, western blot analysis indicated that ALDH1A1 and keratocan expression levels were significantly greater in the hiPSC-CSKs than in the control cells. In addition, hiPSC-CSKs were not transformed into fibroblasts or myofibroblasts. Conclusion: We established an innovative and effective method to generate CSKs via the EB-based differentiation of hiPSCs, which might be employed for cell-based therapy of corneal stromal opacities.

Background: Pathological angiogenesis and stromal fibrosis after ocular chemical injury are primary drivers of corneal opacification and permanent vision loss. Topical administration of anti-VEGFA antibody is hampered by rapid tear clearance and poor penetration across the corneal epithelial barrier, resulting in insufficient intraocular drug accumulation and suboptimal therapeutic efficacy. Although intraocular injection elevates local drug concentration, this invasive procedure carries risks of complications and is not suitable for long-term repeated treatment. This study constructed red cabbage-derived exosome-like nanovesicles (Rabexo) to load an anti-VEGFA antibody, formulated into PVA/HA hydrogel, aiming to develop a topical sustained-release ocular delivery system for alleviating corneal angiogenic and fibrotic lesions. Methods: Rabexo was isolated and physicochemically characterized. Anti-VEGFA antibody was encapsulated into Rabexo via electroporation to prepare aV-Rabexo, which was further incorporated into commercial PVA/HA hydrogel. Cellular uptake, anti-angiogenic functions were verified in vitro, and therapeutic efficacy was evaluated in a mouse corneal alkali burn model via ophthalmic topical administration. Results: The prepared Rabexo showed uniform size and favorable colloidal stability with 40.3% antibody encapsulation efficiency. aV-Rabexo exhibited stronger in vitro anti-migration, anti-proliferation and anti-tube formation effects than free antibody. In vivo, aV-Rabexo-Gel substantially suppressed corneal neovascular area and length, restored stromal collagen arrangement, and downregulated CD31, VEGFA and α-SMA expression at day 14 post-injury, with statistically significant differences compared with the free antibody gel. Conclusions: This plant-derived nanocarrier hydrogel system realizes synergistic therapeutic effects via nanocarrier delivery, antibody neutralization and prolonged ocular retention. With advantages of easy production and low immunogenicity, it provides a promising non-surgical strategy for treating ocular surface pathological angiogenesis and fibrosis.