The efficacy and safety of combination therapy of repeated low-level red light and defocus-incorporated multiple segments spectacle lenses for myopia control in children: the study protocol for a 12-month, randomized, parallel-controlled, and single-center clinical trial.

BACKGROUND: Myopia is increasing in prevalence worldwide. Combination therapy showed a better effect on myopia control than monotherapy. Repeated low-level red light therapy (RLRL) therapy and defocus-incorporated multiple segment (DIMS) spectacle lenses have been reported to retard myopia progression significantly. However, whether these two therapies are better than one is still unknown. The present study aims to report the study protocol of a trial designed to evaluate the efficacy and safety of combination therapy of RLRL and DIMS versus DIMS alone for reducing the progression of myopia among Chinese school-aged children. METHODS: This study is a 12-month, randomized, parallel-controlled, single-center clinical trial. We will recruit children aged 8-12 years with spherical equivalence (SE) between - 0.50 D and - 6.00 D under cycloplegia in both eyes. We will recruit 66 participants with an allocation ratio of 1:1 from our hospital. Participants in the intervention group will be treated with an RLRL therapy device twice a day from Monday to Friday at home, 3 min per session, with a minimum interval of 4 h, under the supervision of their parents/guardians. They will wear DIMS spectacles for myopia correction during the day. Participants in the control group will not receive the RLRL therapy and will only wear DIMS spectacles to correct myopia. Participants from both groups will attend the hospital every 6 months. The primary outcome is the change in axial length at 12 months. Secondary outcomes include changes in refraction under cycloplegia, optical coherence tomography (OCT), multifocal electroretinogram (mfERG), color vision, and participants' self-reporting of adverse events at 12 months. DISCUSSION: This study will report the efficacy and safety outcome of the combination therapy of RLRL and DIMS versus DIMS for school-aged children with myopia in detail. TRIAL REGISTRATION: ChiCTR2300075398. Registered 4 September 2023. https://www.chictr.org.cn/bin/project/edit?pid=200751 .

Ocular biometric characteristics of Han ethnicity in Tianjin and Uyghur ethnicity in Xinjiang undergoing cataract surgery.

AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.

Socioeconomic disparities and green space associated with myopia among Chinese school-aged students: A population-based cohort study.

Background: There is increasing evidence on the link between environmental factors and myopia in children and adolescents, yet with inconsistent conclusions. We investigated the associations between socioeconomic inequalities and green space with myopia in school-aged students participating in the Tianjin Child and Adolescent Research of Eye (TCARE) study. Methods: We obtained data from a population-based dynamic cohort study conducted in Tianjin, China, in 2021 and followed up in 2022. We included 1 245 271 participants from 16 districts with an average age of 11.6 years (standard deviation = 3.3) in our analysis. We synthesized their area-level SES through a prediction model that combined economic, educational, and health care variables and assessed the greenness levels surrounding the school using the Normalized Difference Vegetation Index (NDVI) based on data obtained through satellite remote sensing. We performed generalised linear mixed effects analyses for each myopia outcome separately, with adjustments for students' sex, years of education completed, and the school's geographical location. Results: We observed that students living in low SES areas had the highest prevalence of myopia (60.7%) in the last screening in 2022, as well as a higher incidence of one-year myopia (26.4%) compared to those residing in middle SES areas (22.7%). With a 0.1 increase in the 250, 500, and 1000 m buffer NDVI, the prevalence of myopia dropped by 6.3% (odds ratio (OR) = 0.937; 95% confidence interval (CI) = 0.915, 0.960), 7.7% (OR = 0.923; 95% CI = 0.900, 0.946), and 8.7% (OR = 0.913; 95% CI = 0.889, 0.937), respectively. The interaction analysis showed that low SES and low greenness exacerbate the prevalence of myopia. Findings from longitudinal analyses consistently demonstrated a correlation between higher values of NDVI and a slower progression of myopia. These findings remained robust across sensitivity analyses, including for variables on parental myopia and students' behaviors. Conclusions: Exposure to green spaces could play a crucial role in slowing the progression of myopia among school-aged students. Myopia control policies should prioritise young populations residing in low SES areas with limited access to green spaces, as they face the highest potential risks.

The Myopia Prevalence and Association With Physical Activity Among Primary School Students Aged 6-12 Years: A Cross-Sectional Study in Tianjin, China.

Purpose: This study aimed to investigate the prevalence of myopia and determine the association between physical activity and risk of myopia among primary school students in Tianjin, China. Methods: A cross-sectional study was conducted among subjects from nine primary schools. All of the subjects underwent visual acuity and spherical equivalent (SE) with noncycloplegic autorefraction measurement. Myopia was defined as an SE refraction ≤-0.50D and an uncorrected visual acuity <5.0 in either eye. Physical activity was measured via the Physical Activity Questionnaire for Children. Data were analyzed using the Pearson χ2 test and binary logistic regression. Stratification analysis by sex was also performed. Results: A total of 2976 participants (1408 boys and 1568 girls) aged six to 12 years (mean age 8.82 years) were included in this study. The overall prevalence of myopia was 52.92%. When stratified according to physical activity, myopia prevalence significantly decreased with increasing physical activity levels (χ2 trend test = 127.63, P < 0.001). In the binary logistic regression analysis, after adjusting for age, sex, and school region, the odds ratio for the association between physical activity and myopia was 0.762 (95% confidence interval, 0.675-0.862, P < 0.001). When stratified by sex, the significant statistical association between physical activity and myopia both can be found in two groups (P < 0.05). Conclusions: Higher levels of physical activity were independently associated with decreased risk of myopia. The significant reverse statistical association between physical activity and myopia can be found in male or female groups. Translational Relevance: Taking part in physical activities may be an effective way to reduce the prevalence of myopia.

Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined with Orthokeratology: A Multicenter Randomized Controlled Trial.

PURPOSE: To investigate the efficacy and safety of repeated low-level red-light (RLRL) therapy combined with orthokeratology among children who, despite undergoing orthokeratology, exhibited an axial elongation of at least 0.50 mm over 1 year. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial (ClinicaTrials.gov identifier, NCT04722874). PARTICIPANTS: Eligible children were 8-13 years of age with a cycloplegic spherical equivalent refraction of -1.00 to -5.00 diopters at the initial orthokeratology fitting examination and had annual axial length (AL) elongation of ≥0.50 mm despite undergoing orthokeratology. Forty-eight children were enrolled from March 2021 through January 2022, and the final follow-up was completed in March 2023. METHODS: Children were assigned randomly to the RLRL therapy combined with orthokeratology (RCO) group or to the orthokeratology group in a 2:1 ratio. The orthokeratology group wore orthokeratology lenses for at least 8 hours per night, whereas the RCO group received daily RLRL therapy twice daily for 3 minutes in addition to orthokeratology. MAIN OUTCOME MEASURES: The primary outcome was AL change measured at 12 months relative to baseline. The primary analysis was conducted in children who received the assigned intervention and completed at least 1 follow-up after randomization using the modified intention-to-treat principle. RESULTS: Forty-seven children (97.9%) were included in the analysis (30 in the RCO group and 17 in the orthokeratology group). The mean axial elongation rate before the trial was 0.60 mm/year and 0.61 mm/year in the RCO and orthokeratology groups, respectively. After 12 months, the adjusted mean AL changes were -0.02 mm (95% confidence interval [CI], -0.08 to +0.03 mm) in the RCO group and 0.27 mm (95% CI, 0.19-0.34 mm) in the orthokeratology group. The adjusted mean difference in AL change was -0.29 mm (95% CI, -0.44 to -0.14 mm) between the groups. The percentage of children achieving an uncorrected visual acuity of more than 20/25 was similar in the RCO (64.3%) and orthokeratology (65.5%) groups (P = 0.937). CONCLUSIONS: Combining RLRL therapy with orthokeratology may offer a promising approach to optimize axial elongation control among children with myopia. This approach also potentially allows children to achieve satisfactory visual acuity, reducing daytime dependence on corrective eyewear. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

AS101 regulates the Teff/Treg balance to alleviate rabbit autoimmune dacryoadenitis through modulating NFATc2.

Sjögren's syndrome (SS) dry eye can cause ocular surface inflammation and lacrimal gland (LG) damage, leading to discomfort and potential vision problems. The existing treatment options for SS dry eye are currently constrained. We investigated the possible therapeutic effect and the underlying mechanism of AS101 in autoimmune dry eye. AS101 was injected subconjunctivally into a rabbit model of autoimmune dacryoadenitis and its therapeutic effects were determined by evaluating clinical and histological scores. The expressions of effector T cells (Teff)/regulatory T cells (Treg)-related transcription factors and cytokines, inflammation mediators, and transcription factor NFATc2 were measured by quantitative real-time PCR and/or Western blot both in vivo and in vitro. Additionally, the role of NFATc2 in the immunomodulatory effects of AS101 on T cells was explored by co-culturing activated peripheral blood lymphocytes (PBLs) transfected with NFATc2 overexpression lentiviral plasmid with AS101. AS101 treatment potently ameliorated the clinical severity and reduced the inflammation of LG. Further investigation revealed that AS101 treatment led to decreased expression of Th1-related genes (T-bet and IFN-γ) and Th17-related genes (RORC, IL-17A, IL-17F, and GM-CSF) and increased expression of Treg-related gene Foxp3 in vivo and in vitro. Meanwhile, AS101 suppressed the expression of TNF-α, IL-1ß, IL-23, IL-6, MMP-2, and MMP-9. Mechanistically, AS101 downregulated the expression of NFATc2 in inflamed LGs. Overexpression of NFATc2 in activated PBLs partially blunted the effect of AS101 on Teff suppression and Treg promotion. In conclusion, AS101 is a potential regulator of Teff/Treg cell balance and could be an effective treatment agent for SS dry eye.

INOS ablation promotes corneal wound healing via activation of Akt signaling.

Corneal injury leads to impaired normal structure of the cornea. Improving the wound healing process in epithelial cells significantly contributes to ocular damage treatments. Here, we aimed to investigate the potential mechanisms of nitric oxide (NO) and its mediator, inducible nitric oxide synthase (iNOS), in the process of corneal wound healing. We established a corneal injury model of iNOS-/- mice, and treated human corneal epithelial cell lines (HCE-2) with the iNOS inhibitor L-INL, with or without NO replenishment by supplying sodium nitroferricyanide dihydrate (SNP). Our findings showed that inhibition of NO/iNOS accelerated corneal repair, enhanced uPAR (a receptor protein indicating the migration ability), and improved epithelial cell migration. Furthermore, NO/iNOS ablation activated Akt phosphorylation, reduced neutrophil marker protein MPO expression, and downregulated the transcription of inflammation cytokines CXCL-1, CXCL-2, IL-1ß, IL-6, and TNF-α. However, the protective effects of NO/iNOS inhibition are significantly reduced by NO replenishment when treated with SNP. Therefore, we confirmed that inhibiting NO/iNOS improved the corneal wound healing by facilitating epithelial cell migration and reducing inflammatory reactions, which might be related to the activation of the Akt signaling pathway.

Evaluating the microcirculation of the dome-shaped macula and its complications in adults with highly myopic eyes by swept-source optical coherence tomography angiography.

PURPOSE: The aim of this study was to investigate the microcirculatory characteristics of the dome-shaped macula (DSM), its complications in highly myopic eyes and to explore the factors associated with a DSM. METHODS: This cross-sectional case-control study included a total of 98 subjects (98 eyes): 49 eyes with DSM and 49 eyes without DSM. The axial length (AL) of the myopic eyes was matched 1:1 to eliminate the effect of AL differences on the results. Choroidal (CT) and scleral thickness (ST) and other structural parameters were assessed by swept-source optical coherence tomography (SS-OCT). OCT angiography was used to measure microcirculatory parameters in highly myopic eyes. RESULTS: Subjects with DSM had thinner subfoveal choroidal thickness (46.01 ± 13.25 vs. 81.62 ± 48.26 µm; p < 0.001), thicker subfoveal scleral thickness (SFST; 331.93 ± 79.87 vs. 238.74 ± 70.96 µm; p < 0.001) and thinner foveal CT (66.86 ± 24.65 vs. 107.85 ± 52.65 µm; p < 0.001) compared to subjects without DSM. The foveal choroidal perfusion area (0.72 ± 0.04 vs. 0.76 ± 0.04 mm2; p < 0.001) and foveal choroidal vascularity index (0.15 ± 0.04 vs. 0.33 ± 0.14; p < 0.001) were significantly lower in eyes with DSM. Retinoschisis (81.6% vs. 38.8%; p < 0.001) was more common in eyes with DSM. Eyes with horizontal DSM had worse best-corrected logMAR visual acuity than eyes with round DSM (0.34 ± 0.22 vs. 0.23 ± 0.22; p = 0.03). DSM height (98.95 ± 65.17 vs. 104.63 ± 44.62 µm; p = 0.05) was lower in the horizontal DSM. SFST (OR = 1.06, p = 0.04) and foveal choroidal vascularity index (OR = 0.711, p = 0.02) were significantly associated with DSM. DSM width (p < 0.001), foveal choroidal perfusion area (p = 0.01), foveal choriocapillaris perfusion area (p = 0.02) and parafoveal choroidal vascularity index (p = 0.03) were the most significantly associated factors with DSM height. CONCLUSIONS: The microcirculatory characteristics of eyes with DSM differed from those without DSM. Microcirculatory abnormalities were significantly associated with a DSM. The height of the DSM was associated with decreased blood perfusion.

Effectiveness of repeated low-level red light in myopia prevention and myopia control.

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.

Dimethyl itaconate inhibits antigen-specific Th17 cell responses and autoimmune inflammation via modulating NRF2/STAT3 signaling.

Pathogenic Th17 cells play a crucial role in autoimmune diseases like uveitis and its animal model, experimental autoimmune uveitis (EAU). Dimethyl itaconate (DMI) possesses potent anti-inflammatory effects. However, there is still a lack of knowledge about the role of DMI in regulating pathogenic Th17 cells and EAU. Here, we reported that intraperitoneal administration of DMI significantly inhibited the severity of EAU via selectively suppressing Th17 cell responses. In vitro antigen stimulation studies revealed that DMI dramatically decreased the frequencies and function of antigen-specific Th17, but not Th1, cells. Moreover, DMI hampered the differentiation of naive CD4+ T cells toward pathogenic Th17 cells. DMI-treated DCs produced less IL-1ß, IL-6, and IL-23, and displayed an impaired ability to stimulate antigen-specific Th17 activation. Mechanistically, DMI activated the NRF2/HO-1 pathway and suppressed STAT3 signaling, which subsequently restrains p-STAT3 nuclear translocation, leading to decreased pathogenic Th17 cell responses. Thus, we have identified an important role for DMI in regulating pathogenic Th17 cells, supporting DMI as a promising therapy in Th17 cell-driven autoimmune diseases including uveitis.

Morphological characteristics of the foveal avascular zone in pathological myopia and its relationship with macular structure and microcirculation.

PURPOSE: To explore the characteristics of macular structure, microcirculation, and foveal avascular zone (FAZ) morphology in pathological myopia and to research the associations between these factors and pathological myopia. METHODS: This is a cross-sectional study. The study included 103 eyes with non-high myopia and 206 eyes with high myopia (139 with simple high myopia and 67 with pathological myopia). Macular structural and microcirculation parameters were determined using optical coherence tomography angiography (OCTA). The FAZ morphological parameters were measured manually using Image J software. Correlations between pathological myopia and various factors were analyzed. RESULTS: Patients with pathological myopia had a thinner retinal thickness (RT) and choroidal thickness (CT) and a lower retinal superficial vascular density (SVD), retinal deep vascular complex density (DVD), choriocapillaris perfusion area (CCPA), and choroidal vascularity index (CVI) (all P < 0.05). Patients with pathological myopia had a larger FAZ area, perimeter, major axis, minor axis, acircularity index (AI), and lower circularity index (CI) (all P < 0.01). The axial length (AL), the major axis of the superficial FAZ, CI, and AI were significantly correlated with myopia severity (all P < 0.05). CONCLUSIONS: Patients with pathological myopia exhibited worse macular microcirculation and thinner macular retina and choroid. The FAZ in pathological myopia was larger and more irregular. The AL, CI, and AI were significantly associated with myopia severity. Thus, CI and AI might serve as new indicators for monitoring the progression of myopia. Further investigations should be performed. TRIAL REGISTRATION: Clinical Trials.gov Identifier: ChiCTR2100046590.

Retinal and choroidal structure and vascularity in Chinese emmetropic and myopic children.

PURPOSE: This study evaluated the structural features of the retinal and choroidal regions and their correlations with ocular biometric and vascular parameters in Chinese children using optical coherence tomography angiography (OCTA). METHODS: A total of 159 children, 6-13 years of age, were included in this prospective study. The sample consisted of 55 emmetropes (spherical equivalent ≤ +0.75 and > -0.50 D), 53 low-moderate myopes (≤ -0.50 to > -6.00 D) and 51 high myopes without pathological changes (≤ -6.00 D). Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Swept-source optical coherence tomography/OCTA was used to assess the macular structures and vascular characteristics in a 6 × 6 mm region centred on the macula. RESULTS: In a comprehensive analysis adjusting for age, sex, AL, macular blood perfusion, intraocular pressure and anterior segment parameters, retinal thickness (RT) showed a significant positive association with deep retinal vascular density and superficial retinal vascular density in the foveal area, but not with AL. Moreover, RT exhibited a significant negative association with AL in the parafoveal and perifoveal regions. Further, a significant positive correlation was observed between choroidal thickness and both choroidal vascular volume and choriocapillaris perfusion area, along with a negative correlation with AL across the entire macular region. CONCLUSIONS: This study showed that the thickness of retina and choroid in Chinese children was not only associated with AL but also showed dynamic properties such as the blood perfusion of the retina and choroid, particularly in the foveal area.

Interaction between parental myopia and children lifestyle on the incidence of myopia among children aged 6-18 years: a cross-sectional study in Tianjin, China.

OBJECTIVES: This study aimed to explore the influence of the interaction between parental myopia and lifestyle on myopia among school-age children. DESIGN: Cross-sectional study. SETTING: This study used data from the Tianjin Child and Adolescent Research of Eye between August and October 2022. PARTICIPANTS: A total of 49 035 participants between 6 and 18 years of age were eligible for this study. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the interaction between eye-healthy lifestyle and parental myopia on myopia. Parental myopia and eye-healthy lifestyle were ascertained by a Child and Adolescent Behavior Questionnaire. The lifestyle risk score (LRS) of eye health was calculated based on beta-coefficient in the backward regression model. The interaction between LRS and parental myopia was analysed by multivariate logistic regression. The predictive value of different predicted models was estimated using receiver operating characteristic curves. Multiple linear regression was used to evaluate the associations of lifestyle risk factors and parental myopia with spherical equivalent refraction, which were defined as the secondary outcomes. RESULTS: A total of 31 839 participants aged 6-18 years were included, and the myopia prevalence was 55.46%. Eye-healthy lifestyle and parental myopia were significantly associated with myopia, as was interaction. The predictive value for LRS & parental myopia was 0.714 (95% CI: 0.709 to 0.720), which was higher than LRS (0.693, 95% CI: 0.687 to 0.699) and parental myopia (0.710, 95% CI: 0.704 to 0.716) separately. CONCLUSIONS: High-risk lifestyles of myopia and parental myopia were significantly associated with a higher risk of myopia, and the combination had the strongest effect. For children, lifestyle adjustment should be prioritised in preventing myopia, especially for those with parental myopia.

The Effects of Repeated Low-Level Red-Light Therapy on the Structure and Vasculature of the Choroid and Retina in Children with Premyopia.

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.

Relative corneal refractive power shift and inter-eye differential axial growth in children with myopic anisometropia treated with bilateral orthokeratology.

PURPOSE: To investigate the relationship between relative corneal refractive power shift (RCRPS) and axial length growth (ALG) in bilateral myopic anisometropes treated with orthokeratology. METHODS: A total of 102 children with myopic anisometropia in this prospective interventional study were randomly assigned to the spectacle group and orthokeratology group. Axial length (AL) and corneal topography was measured at baseline and the 12-month follow-up visit. ALG was defined as the difference between the two measurements, and RCRPS profiles were calculated from two axial maps obtained. RESULTS: In the orthokeratology group, the ALG in the more myopic eye (0.06 ± 0.15 mm) was significantly smaller than that in the less myopic eye (0.15 ± 0.15 mm, p < 0.001), and the interocular difference in AL significantly decreased following 1-year treatment, from 0.47 ± 0.32 to 0.38 ± 0.28 mm (p < 0.001). However, in the spectacle group, the ALG was similar between the two eyes, and the interocular difference in AL did not change significantly over one year (all p > 0.05). The interocular difference in ALG in the orthokeratology group was significantly correlated with the interocular difference in RCRPS (dRCRPS, ß=-0.003, p < 0.001) and the interocular difference in baseline AL (ß=-0.1179, p < 0.001), with R2 being 0.6197. CONCLUSION: Orthokeratology was effective in decreasing the magnitude of anisometropia. The interocular variation in RCRPS is an important factor accounting for the reduction of interocular ALG difference in anisomyopic children post-orthokeratology. These results provide insight into establishing eye-specific myopia control guidelines during orthokeratology treatment for myopic anisometropes.

Relationship between the structure and microcirculation of the optic disc region and myopic traction maculopathy in highly myopic eyes.

PURPOSE: To explore the characteristics and influencing factors structural and microcirculatory of optic disc and peripapillary tissue in eyes with myopia traction maculopathy (MTM). METHODS: There were 100 eyes from 77 patients in this study. We used 1:1 matching axial length in myopic eyes. Patients were divided into two groups according to the presence or absence of MTM. Fundus structure parameters were obtained by swept source optical coherence tomography (SS-OCT), and the optic disc microcirculation parameters were obtained by OCT angiography (OCTA). RESULTS: MTM group were older (P = 0.001) and had poorer Best-corrected Visual Acuity (BCVA) (P = 0.011), the optic disc-fovea distance (DFD) was longer (P < 0.019), optic disc tilt was greater (P < 0.001), area of peripapillary atrophy (PPA) was larger (P < 0.001), and PPA/optical disc area (ONH) was higher (P < 0.001). The peripapillary scleral thickness (PST) was lower in the MTM group (P < 0.001). The mean peripapillary choroidal thickness (PCT) (P < 0.001) and PCT in the 10 orientations were significantly lower in the MTM group than in the NMTM group (all P < 0.01). Vascular density in the nasosuperior (NS) region of the optic disc was significantly lower in the MTM group (P = 0.037). The generalized estimating equation suggested that PPA area (P = 0.028), mean PCT (P = 0.008), superior PCT (P = 0.027), inferonasal PCT (P = 0.040), temporoinferior PCT (P = 0.013), and PST (P = 0.046) correlated with MTM. Age, axial length, optic disc tilt, PPA area, mean PCT, and optic disc central zone (0-2 mm) vascular density (all P < 0.05) were significantly correlated with PST. CONCLUSIONS: The enlarged PPA area and thinner PCT and PST in eyes with MTM are more significant. Lower PST in high myopia was related to abnormalities of PCT and microcirculation. TRIAL REGISTRATION: Clinical Trial Registration number: ChiCTR2100046590.

Integrated DNA Methylation and Transcriptomics Analyses of Lacrimal Glands Identify the Potential Genes Implicated in the Development of Sjögren's Syndrome-Related Dry Eye.

Purpose: Sjögren's syndrome-related dry eye (SS-related dry eye) is an intractable autoimmune disease characterized by chronic inflammation of lacrimal glands (LGs), where epigenetic factors are proven to play a crucial role in the pathogenesis of this disease. However, the alteration of DNA methylation in LGs and its role in the pathogenesis of SS-related dry eye is still unknown. Here, we performed an integrated analysis of DNA methylation and RNA-Seq data in LGs to identify novel DNA methylation-regulated differentially expressed genes (MeDEGs) in the pathogenesis of SS-related dry eye. Methods: The DNA methylation and transcription profiles of LGs in NOD mice at different stages of SS-related dry eye (4-, 8-, 12- and 16 weeks old) were generated by reduced representation bisulfite sequencing (RRBS) and RNA-Seq. The differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were analyzed by MethylKit R package and edgeR. Correlation analysis between methylation level and mRNA expression was conducted with R software. The functional correlation of DMGs and DEGs was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, LG tissues from another litter of NOD mice were collected for methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) to validate the methylation and expression levels of key genes. CD4+ cell infiltration of LGs was detected by immunofluorescence staining. Results: Hypermethylation of LGs was identified in NOD mice with the progression of SS-related dry eye and the DMGs were mainly enriched in the GTPases activation and Ras signaling pathway. RNA-seq analysis revealed 1321, 2549, and 3712 DEGs in the 8-, 12- and 16-week-old NOD mice compared with 4-week-old normal control mice. For GO analysis, the DEGs were mainly enriched in T cell immune responses. Further, a total of 140 MeDEGs were obtained by integrated analysis of methylome and transcriptome, which were primarily enriched in T cell activation, proliferation and differentiation. Based on the main GO terms and KEGG pathways of MeDEGs, 8 genes were screened out. The expression levels of these key genes, especially Itgal, Vav1, Irf4 and Icosl, were verified to elevate after the onset of SS-related dry eye in NOD mice and positively correlated with the extent of inflammatory cell infiltration in LGs. Immunofluorescence assay revealed that CD4+ cell infiltration dramatically increased in LGs of SS-related dry eye mice compared with the control mice. And the expression levels of four genes showed significantly positive correlation with the extent of CD4+ cell infiltration in LGs. MSP showed the hypomethylation of the Irf4 and Itgal promoters in NOD mice with SS-related dry eye compared to control group. Conclusion: Our study revealed the critical role of epigenetic regulation of T cell immunity-related genes in the progression of SS-related dry eye and reminded us that DNA methylation-regulated genes such as Itgal, Vav1, Irf4 and Icosl may be used as new targets for SS-related dry eye therapy.

Comparison of two different orthokeratology lenses and defocus incorporated soft contact (DISC) lens in controlling myopia progression.

BACKGROUND: To compare axial elongation in 8-11-year-old myopes wearing orthokeratology (OK) lenses with different back optic zone diameters (BOZD), defocus incorporated soft contact (DISC) lenses, and single-vision soft contact lenses (SCLs). METHODS: A total of 122 children (aged 8-11 years) with spherical equivalent refraction (SER) between - 1.00 D and - 4.00 D were enrolled in this prospective study and randomly assigned to four groups: 5.0 mm-BOZD OK, 6.2 mm-BOZD OK, DISC, and single-vision SCLs. Children in each group were further divided into subgroups stratified by the average baseline SER: low myopic eyes (SER: - 1.00 D to - 2.50 D) and moderate myopic eyes (SER: - 2.50 D and over). Axial length (AL) was measured at baseline and after one year. RESULTS: The 5.0 mm-BOZD OK, 6.2 mm-BOZD OK, and DISC groups exhibited significantly slower AL elongation than the SCL group. The proportion of slow progressors (AL elongation ≤ 0.18 mm/year) in the first three groups was 42%, 23%, and 29%, respectively. Furthermore, one-year AL elongation was significantly smaller in the 5.0 mm-BOZD OK group compared with the 6.2 mm-BOZD OK group. Regardless of SER, children in the 5.0 mm-BOZD OK and DISC groups showed comparably slower AL elongation than those in the SCL group. However, fitting with 6.2 mm-BOZD OK lenses significantly retarded AL elongation in moderate myopic eyes, but not in low myopic eyes. CONCLUSIONS: Overall, 5.0 mm-BOZD OK lenses, 6.2 mm-BOZD OK lenses, and DISC lenses were effective in retarding AL elongation in 8-11-year-old myopes compared with single-vision SCLs, but for children with SER less than - 2.50 D, fitting with 5.0 mm-BOZD OK lenses and DISC lenses yielded better myopia control efficacy compared to wearing single-vision SCLs or 6.2 mm-BOZD OK lenses.

Mettl3 induced miR-338-3p expression in dendritic cells promotes antigen-specific Th17 cell response via regulation of Dusp16.

Pathogenic Th17 cells are critical drivers of multiple autoimmune diseases, including uveitis and its animal model, experimental autoimmune uveitis (EAU). However, how innate immune signals modulate pathogenic Th17 responses remains largely unknown. Here, we showed that miR-338-3p endowed dendritic cells (DCs) with an increased ability to activate interphotoreceptor retinoid-binding protein (IRBP)1-20 -specific Th17 cells by promoting the production of IL-6, IL-1ß, and IL-23. In vivo administration of LV-miR-338-infected DCs promoted pathogenic Th17 responses and exacerbated EAU development. Mechanistically, dual-specificity phosphatase 16 (Dusp16) was a molecular target of miR-338-3p. miR-338-3p repressed Dusp16 and therefore strengthened the mitogen-activated protein kinase (MAPK) p38 signaling, resulting in increased production of Th17-polarizing cytokines and subsequent pathogenic Th17 responses. In addition, methyltransferase like 3 (Mettl3), a key m6A methyltransferase, mediated the upregulation of miR-338-3p in activated DCs. Together, our findings identify a vital role for Mettl3/miR-338-3p/Dusp16/p38 signaling in DCs-driven pathogenic Th17 responses and suggest a potential therapeutic avenue for uveitis and other Th17 cell-related autoimmune disorders.

Time trends in myopia and high myopia prevalence in young university adults in China.

AIM: To investigate time trends in myopia and high myopia prevalence over 6y among young university adults in China. METHODS: This is a 6-year series cross-sectional study from 2016 to 2021. Totally 4910 freshmen were enrolled and completed a questionnaire concerning age, gender, and disease history. Students with eye diseases were excluded after a detailed eye examination. The refractive status was measured by non-cycloplegic objective refraction and ocular parameters were measured by Lenstar 900. The examination followed the same protocol each year. Trends over time in myopia and high myopia prevalence, as well as ocular biometry parameters, were analyzed. RESULTS: From 2016 to 2021, the axial length (AL) and corneal radius (CR) increased significantly (P=0.002 for AL; P=0.04 for CR). However, the spherical equivalent (SE) and the ratio of axial length to the corneal radius (AL/CR) did not change significantly (P=0.59 for SE; P=0.24 for AL/CR). The frequency of AL ≥26.0 mm increased from 26.6% in 2016 to 29.3% in 2021 (P=0.05 for trend). The prevalence of myopia and high myopia did not change significantly in our study (P≥0.18). Compared to a similar cross-sectional study conducted 10 years ago, the prevalence of myopia decreased significantly (94.9% vs 91.8%, P<0.001). Whereas the prevalence of high myopia increased largely (18.12% vs 27.6%, P<0.001). CONCLUSION: The prevalence of high myopia increases in young university adults during 10y period. Myopia control should begin earlier in childhood. However, these interventions are still needed for high myopia even in young adulthood.