Introduction To evaluate the 6-month efficacy and safety of 650 nm low-level red light (LLRL) for myopia control in children. Methods This was a single-center, single-masked randomized controlled trial. A total of 224 children aged 6–12 years with spherical equivalent error (SER) of − 6 diopter (D) to − 0.5 D were enrolled, and were randomized to LLRL group or control group. Children in the LLRL group underwent treatment twice daily, each lasting for 3 min, there was an interval of at least 4 h between treatments. Children in both groups were allowed to wear single-vision spectacles; no additional intervention was given to the control. The primary outcomes included change in cycloplegic SER and change in axial length (AL) during 6 months. Results The median 6-month changes in AL of the LLRL and control groups were − 0.06 mm (interquartile range, IQR − 0.15, 0) and 0.14 mm (IQR 0.07, 0.22), respectively. The difference between groups was significant (Z = 10.021, p < 0.001). The median 6-month changes in SER were 0.125 D (IQR 0, 0.375) and − 0.25 D (IQR − 0.5, 0) for the LLRL and control groups, respectively. The difference between groups was significant (Z = 8.827, p < 0.001). Compared with the control, the proportion of children with hyperopic shift in the LLRL group was higher (51.65% vs. 3.41%, p < 0.001), and the proportion of children with shortened AL in the LLRL group was higher (63.74% vs. 2.27%, p < 0.001). No adverse event was observed. Conclusion 650 nm LLRL significantly slowed down the myopia progression in children aged 6–12 years, and there was no observable side effect in the short term.

Importance: Treatments are needed to slow progression of or reduce incidence of myopia.Objective: To evaluate the efficacy and safety of daily 650-nm low-level red light (LLRL) for myopia treatment.Design, Setting, and Participants: Single-masked, randomized clinical trial at 1 site in China. Baseline measurements were completed from August to September 2021. Participants were children aged 6 to 12 years with spherical equivalent error (SER) of −6 diopters (D) to 3 D. Data were analyzed from March to July 2023.Interventions: Irradiation daily with 650-nm LLRL for 3 minutes twice daily 4 or more hours apart or no intervention.Main Outcomes and Measures: Primary outcomes were changes in cycloplegia SER and axial length (AL) at 6- and 12-month follow-up visits. Safety was assessed on masked fundus photograph evaluations.Results: A total of 336 children were randomly allocated into the LLRL group or control group in a 1:1 ratio. The control group contained 86 female patients (51.2%), and the treatment group contained 90 female patients (53.6%). The mean (SD) age, SER, and AL were 9.0 (1.9) years, −1.3 (1.5) D, and 23.8 (1.0) mm for all patients. A total of 161 (95.8%) in the LLRL group and 159 (94.6%) in the control group returned for the 6-month follow-up. A total of 157 (93.5%) in the LLRL group and 152 (90.5%) in the control group returned for the 12-month follow-up. Mean (SD) changes in SER were 0.15 (0.16) D and −0.26 (0.21) D for the LLRL group and the control group, respectively (difference, −0.41 D; 95% CI, −0.48 to −0.34 D; P < .001), at 6 months and 0.24 (0.27) D and −0.65 (0.33) D for the LLRL group and the control group, respectively (difference, −0.89 D; 95% CI, −0.95 to −0.83 D; P < .001), at 12 months. Mean (SD) changes in AL were −0.06 (0.08) mm and 0.13 (0.12) mm for the LLRL group and control group, respectively (difference, 0.19 mm; 95% CI, 0.16 to 0.22 mm; P < .001), at 6 months and −0.11 (0.10) mm and 0.26 (0.16) mm for the LLRL group and control group, respectively (difference, 0.37 mm; 95% CI, 0.34 to 0.40 mm; P < .001). Masked fundus photograph review did not identify retinal changes in either group.Conclusions and relevance: These findings suggest daily use of 650-nm LLRL for 1 year can slow progression of SER and AL without safety concerns identified. Confirmation of these findings at independent sites seems warranted, as well as determining whether these effects can be sustained with or without continued treatment and whether LLRL has any effect on pathological myopia.Trial Registration: ChiCTR2200058963

Importance: Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye disease (DED). Medical and surgical management for DED is limited; therefore, new treatment options are sought.Objective: To evaluate the efficacy and safety of SHR8058 (perfluorohexyloctane) eye drops in Chinese patients with DED associated with MGD through 57 days.Design, Setting, and Participants: This was a randomized, multicenter, double-masked, saline-controlled, phase 3 clinical trial conducted from February 4, 2021, to September 7, 2022. Patients were recruited from the departments of ophthalmology in 15 hospitals in China. Patients with DED associated with MGD were enrolled between February 4 and July 1, 2021. The diagnosis was based on patient complaint of DED symptoms, an ocular surface disease index of 25 or higher, tear film break-up time of 5 seconds or less, Schirmer I test without anesthesia results of 5 mm or more at 5 minutes, total corneal fluorescein staining (tCFS) score of 4 to 11, and an MGD score of 3 or higher.Interventions: Eligible participants were randomly assigned 1:1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]) 4 times per day.Main Outcomes and Measures: The primary end points were the changes from baseline in tCFS and eye dryness scores at day 57.Results: A total of 312 participants were included in the analysis: 156 (mean [SD] age, 45.4 [15.2] years; 118 female [75.6%]) in the perfluorohexyloctane group and 156 (mean [SD] age, 43.7 [15.1] years; 127 female [81.4%]) in the NaCl group. Both primary end points were achieved, ie, changes from baseline at day 57 of tCFS score (mean [SD], −3.8 [2.7] vs −2.7 [2.8]) and eye dryness score (mean [SD], −38.6 [21.9] vs −28.3 [20.8]) in the perfluorohexyloctane group were superior to the control group, with estimated mean differences of −1.14 (95% CI, −1.70 to −0.57; P < .001) and −12.74 (95% CI, −17.20 to −8.28, P < .001), respectively. Improvements on both end points appeared to be noted on day 29 and day 15, respectively, and maintained through day 57. Compared with the control, perfluorohexyloctane eye drops also alleviated symptoms including pain (mean [SD] tCFS score, 26.7 [23.7] vs −18.7 [22.5]; P = .003), awareness of DED symptoms (mean [SD] tCFS score, −38.1 [25.1] vs −23.7 [27.6]; P < .001), and frequency of dryness (mean [SD] tCFS score, −43.3 [23.8] vs −29.1 [24.8]; P < .001). Treatment-emergent adverse events occurred in 34 participants (21.8%) and 40 participants (25.6%) in the perfluorohexyloctane and control groups, respectively.Conclusions and Relevance: Results of this randomized clinical trial demonstrate that perfluorohexyloctane eye drops significantly ameliorated the signs and symptoms of DED associated with MGD with a rapid efficacy as well as satisfactory tolerability and safety through 57 days. Findings support the use of these eye drops if results can be confirmed independently and over longer time periods.Trial Registration: ClinicalTrials.gov Identifier: NCT05515471

Severe dry eye disease causes ocular surface damage, which is highly associated with mitochondrial dysfunction. Mitochondrial transcription factor A (TFAM) is essential for packaging mitochondrial DNA (mtDNA) and is crucial for maintaining mitochondrial function. Herein, we aimed to explore the effect of a decreased TFAM expression on ocular surface damage. Female C57BL/6 mice were induced ocular surface injury by topical administrating benzalkonium chloride (BAC). Immortalized human corneal epithelial cells (HCECs) were stimulated by tert-butyl hydroperoxide (t-BHP) to create oxidative stress damage. HCECs with TFAM knockdown were established. RNA sequencing was employed to analyze the whole-genome expression. Mitochondrial changes were measured by transmission electron microscopy, Seahorse metabolic flux analysis, mitochondrial membrane potential, and mtDNA copy number. TFAM expression and inflammatory cytokines were determined using RT-qPCR, immunohistochemistry, immunofluorescence, and immunoblotting. In both the corneas of BAC-treated mice and t-BHP-induced HCECs, we observed impaired TFAM expression, accompanied by mitochondrial structure and function defects. TFAM downregulation in HCECs suppressed mitochondrial respiratory capacity, reduced mtDNA content, induced mtDNA leakage into the cytoplasm, and led to inflammation. RNA sequencing revealed the absent in melanoma 2 (AIM2) inflammasome was activated in the corneas of BAC-treated mice. The AIM2 inflammasome activation was confirmed in TFAM knockdown HCECs. TFAM knockdown in t-BHP-stimulated HCECs aggravated mitochondrial dysfunction and the AIM2 inflammasome activation, thereby further triggering the secretion of inflammatory factors such as interleukin (IL) -1β and IL-18. TFAM reduction impaired mitochondrial function, activated AIM2 inflammasome and promoted ocular surface inflammation, revealing an underlying molecular mechanism for ocular surface disorders.

Microplastics (MPs) are emerging environmental pollutants that are increasingly being detected in various human tissues. However, their impact on ocular health is underexplored. This study investigated the presence of MPs in tear fluid and meibum of 45 patients with dry eye disease (DED). Various examinations were conducted, including the Schirmer I test, fluorescein tear film break-up time (FBUT) and other dry eye-related assessments. MPs were identified in the tear fluid and meibum and were categorized into five distinct types, with polyethylene (PE) being the most predominant. Notably, PE levels exhibited significant correlations with key DED parameters, such as Schirmer I test scores and FBUT. In in-vitro studies, PE exposure reduced the viability and induced apoptosis of human corneal epithelial cells and conjunctival epithelial cells in a dose-dependent manner. In mouse models, topical exposure to PE drops, which imitate airborne PE exposure, induced typical dry eye signs, reduced goblet cell numbers, and triggered conjunctival inflammation. PE-treated meibomian glands exhibited changes, but these changes were not statistically significant, possibly because of the limited duration of the study. This study is the first to confirm the presence of microplastics (MPs) in human tear fluid and meibum while also offering novel insights into the potential pathogenic effects of airborne MP exposure on ocular health.