To investigate how different light/dark (L/D) cycles and light intensities influence refractive development and form-deprivation myopia (FDM) in mice, and to examine whether these phenotypes are accompanied by changes in retina/RPE circadian rhythm-related genes expression and dopamine levels. Three-week-old C57BL/6 J mice undergoing natural refractive development or monocular FDM (induced by translucent diffusers) were exposed for 4 weeks to three light intensities (10, 300, or 3000 lx) under four light/dark cycles. Refractive error, axial length (AL), Opn4, Cry1, Per3 expression, and dopamine levels in retina/RPE were assessed. Extending photoperiod (from 6L/18D to 12L/12D, 18L/6D, or continuous light) induced significant myopic shifts (increased AL, decreased refraction) in natural refractive development mice at 300 lx and 3000 lx (both P < 0.001), but not at 10 lx. This shift correlated with decreased Opn4 and increased Cry1 and Per3 expression (P < 0.05). Notably, continuous light (CL) at 3000 lx significantly inhibited FDM progression (vs. other photoperiods P < 0.001), accompanied by elevated Opn4 and Cry1. Conversely, one week of CL at 10 lx transiently induced hyperopia in FDM mice. Retinal dopamine content showed no significant correlation with these refractive changes. Light intensity and L/D cycles critically regulate refractive development and myopia progression in mice, with these effects showing stronger associations with alterations in circadian rhythm-related genes than with retinal dopamine levels. Continuous bright light (3000 lx) inhibits FDM, while dim light (10 lx) effects are photoperiod dependent. These findings suggest targeting optimized light exposure and circadian modulation as potential therapeutic strategies.

Early detection of myopia risk and timely intervention are key to reducing the incidence of myopia. This study aimed to construct a myopia prediction model that included perinatal factors and evaluate the correlation between each factor and myopia. A cross-sectional study was conducted. A questionnaire was used to investigate the related factors. The predictors of myopia onset were determined via univariate analysis (Model A), LASSO regression and 10-fold cross validation (Model B). The perinatal factors in Model B were removed to form Model C. Binary logistic regression was used to establish the model. Then, internal and external verification were performed. The differentiation, calibration, and clinical benefits of the three models were compared. A total of 1322 participants with an average age of 7.85 ± 1.58 years were included in the study. Model B included age, axial length (AL), AL to corneal curvature (AL/CR) ratio, steep K (K2) value, parental myopia, and maternal history of gestational hypertension. Neither Model A nor Model C included perinatal factors. Model B had the best discrimination ability in the development, internal validation, and external validation groups and showed the best consistency and clinical benefit in all three groups. After model standardization, the effects of the respective variables on the results were as follows: AL/CR ratio: 59.14, maternal history of gestational hypertension: 44.03, AL: 30.47, K2: 5.65, parental myopia: 4.55, and age: 0.35. A maternal history of gestational hypertension was associated with myopia. The effect of perinatal factors on myopia deserves attention. ChiCTR2200065398. November 3, 2022. ( http://www.chictr.org.cn ).

AIMS:To determine whether inflammatory biomarkers are causal risk factors for more myopic refractive errors. METHODS:Northern Sweden Population Health Study (NSPHS), providing inflammatory biomarkers data; UK Biobank, providing refractive errors data. 95,619 European men and women aged 40 to 69 years with available information of refractive errors and inflammatory biomakers. Inflammatory biomarkers including ADA, CCL23, CCL25, CD6, CD40, CDCP-1, CST5, CXCL-5, CXCL-6, CXCL-10, IL-10RB, IL-12B, IL-15RA, IL-18R1, MCP-2, MMP-1, TGF-β1, TNF-β, TWEAK and VEGF-A were exposures, and spherical equivalent (SE) using the formula SE = sphere + (cylinder/2) was outcome. RESULTS:Mendelian randomization analyses showed that each unit increase in VEGF-A, CD6, MCP-2 were causally related to a more myopic refractive errors of 0.040 D/pg.mL-1 (95% confidence interval 0.019 to 0.062; P = 2.031 × 10-4), 0.042 D/pg.mL-1 (0.027 to 0.057; P = 7.361 × 10-8) and 0.016 D/pg.mL-1 (0.004 to 0.028; P = 0.009), and each unit increase in TWEAK was causally related to a less myopic refractive errors of 0.104 D/pg.mL-1 (-0.152 to -0.055; P = 2.878 × 10-5). Tested by the MR-Egger, weighted median, MR-PRESSO, Leave-one-out methods, our results were robust to horizontal pleiotropy and heterogeneity in VEGF-A, MCP-2, CD6, but not in TWEAK. CONCLUSIONS:Our Mendelian Randomization analysis supported the causal effects of VEGF-A, MCP-2, CD6 and TWEAK on myopic refractive errors. These findings are important for providing new indicators for early intervention of myopia to make myopic eyesight threatening consequences less inevitable.

Myopia is a health issue that has attracted global attention due to its high prevalence and vision-threatening complications. It is well known that the onset and progression of myopia are related to both genetic and environmental factors: more than 450 common genetic loci have been found to be associated with myopia, while near work and outdoor time are the main environmental risk factors. As for many complex traits, gene-environment interactions are implicated in myopia development. To date, several genetic loci have been found to interact with near work or educational level. Gene-environment interaction research on myopia could yield models that provide more accurate risk predictions, thus improving targeted treatments and preventive strategies. Additionally, such investigations might have the potential to reveal novel genetic information. In this review, we summarised the findings in this field and proposed some topics for future investigations.

Clinical relevance:Identification of individuals with a higher risk of developing refractive error under specific gene and environmental backgrounds, especially myopia, could enable more personalized myopic control advice for patients. Background:Refractive error is a common disease that affects visual quality and ocular health worldwide. Its mechanisms have not been elaborated, although both genes and the environment are known to contribute to the process. Interactions between genes and the environment have been shown to exert effects on the onset of refractive error, especially myopia. Axial length elongation is the main characteristic of myopia development and could indicate the severity of myopia. Thus, the purpose of the study was to investigate the interaction between environmental factors and genetic markers of VIPR2 and their impact on spherical equivalence and axial length in a population of Han Chinese children. Methods:A total of 1825 children aged 13~15 years in the Anyang Childhood Eye Study (ACES) were measured for cycloplegic autorefraction, axial length, and height. Saliva DNA was extracted for genotyping three single-nucleotide polymorphisms (SNPs) in the candidate gene (VIPR2). The median outdoor time (2 h/day) was used to categorize children into high and low exposure groups, respectively. Genetic quality control and linear and logistic regressions were performed. Generalized multifactor dimensional reduction (GMDR) was used to investigate gene-environment interactions. Results:There were 1391 children who passed genetic quality control. Rs2071623 of VIPR2 was associated with axial length (T allele, β=-0.11 se=0.04 p=0.006), while SNP nominally interacted with outdoor time (T allele, β=-0.17 se=0.08 p=0.029). Rs2071623 in children with high outdoor exposure had a significant interaction effect on axial length (p=0.0007, β=-0.19 se=0.056) compared to children with low outdoor exposure. GMDR further suggested the existence of an interaction effect between outdoor time and rs2071623. Conclusions:Rs2071623 within VIPR2 could interact with outdoor time in Han Chinese children. More outdoor exposure could enhance the protective effect of the T allele on axial elongation.

Purpose:To explore the relationship of color vision deficiency with myopia progression and axial elongation in Chinese primary school children during a five-year cohort study.Methods:A total of 2849 grade 1 students (aged 7.1 ± 0.4 years) from 11 primary schools were enrolled and followed up for five years. Cycloplegic autorefraction and axial length were measured annually. Color vision testing was performed using Ishihara's test and the City University color vision test.Results:The prevalence of color vision deficiency was 1.68%, with 2.81% in boys and 0.16% in girls. Color-deficient cases consisted of 91.6% deutan and 8.3% protan. Over the five years, the cumulative incidence of myopia was 35.4% (17/48) in the color-vision deficiency group, which was lower than the 56.7% (1017/1794) in the color normal group (P = 0.004). Over the five-year study period, the change in spherical equivalent refraction in the color vision-deficiency group (-1.81 D) was also significantly lower than that in the color normal group (-2.41 D) (P = 0.002).Conclusions:The lower incidence and slower progression of myopia in children with color-vision deficiency over the five-year follow-up period suggest that color-deficient individuals are less susceptible to myopia onset and development.

Purpose: To evaluate the efficacy and safety of atropine for slowing myopia progression and to investigate whether the treatment effect remains constant with continuing treatment. Method: Studies were retrieved from MEDLINE, EMBASE, and the Cochrane Library from their inception to May 2021, and the language was limited to English. Randomized controlled trials (RCTs) and cohort studies involving atropine in at least one intervention and placebo/non-atropine treatment in another as the control were included and subgroup analysis based on low dose (0.01%), moderate dose (0.01%–<0.5%), and high dose (0.5–1.0%) were conducted. The Cochrane Collaboration and Newcastle-Ottawa Scale were used to evaluate the quality of RCTs and cohort studies, respectively. Results: Twelve RCTs and fifteen cohort studies involving 5,069 children aged 5 to 15 years were included. The weighted mean differences in myopia progression between the atropine and control groups were 0.73 diopters (D), 0.67 D, and 0.35 D per year for high-dose, moderate-dose, and low-dose atropine, respectively (χ 2 = 13.76; P = 0.001, I 2 = 85.5%). After removing studies that provided extreme findings, atropine demonstrated a significant dose-dependent effect on both refractive change and axial elongation, with higher dosages of atropine resulting in less myopia progression ( r = 0.85; P = 0.004) and less axial elongation ( r = −0.94; P = 0.005). Low-dose atropine showed less myopia progression (−0.23 D; P = 0.005) and less axial elongation (0.09 mm, P < 0.001) in the second year than in the first year, whereas in high-dose atropine more axial elongation (−0.15 mm, P = 0.003) was observed. The higher dose of atropine was associated with a higher incidence of adverse effects, such as photophobia with an odds ratio (OR) of 163.57, compared with an OR of 6.04 for low-dose atropine and 8.63 for moderate-dose atropine ( P = 0.03). Conclusion: Both the efficacy and adverse effects of atropine are dose-dependent in slowing myopia progression in children. The efficacy of high-dose atropine was reduced after the first year of treatment, whereas low-dose atropine had better efficacy in a longer follow-up period.

ImportanceMyopia in school-aged children is a public health issue worldwide; consequently, effective interventions to prevent onset and progression are required.ObjectiveTo investigate whether SMS text messages to parents increase light exposure and time outdoors in school-aged children and provide effective myopia control.Design, Setting, and ParticipantsThis randomized clinical trial was conducted in China from May 2017 to May 2018, with participants observed for 3 years. Of 528 965 primary school–aged children from Anyang, 3113 were randomly selected. Of these, 268 grade 2 schoolchildren were selected and randomly assigned to SMS and control groups. Data were analyzed from June to December 2021.InterventionsParents of children in the SMS group were sent text messages twice daily for 1 year to take their children outdoors. All children wore portable light meters to record light exposure on 3 randomly selected days (2 weekdays and 1 weekend day) before and after the intervention.Main Outcomes and MeasuresThe co–primary outcomes were change in axial length (axial elongation) and change in spherical equivalent refraction (myopic shift) from baseline as measured at the end of the intervention and 3 years later. A secondary outcome was myopia prevalence.ResultsOf 268 grade 2 schoolchildren, 121 (45.1%) were girls, and the mean (SD) age was 8.4 (0.3) years. Compared with the control group, the SMS intervention group demonstrated greater light exposure and higher time outdoors during weekends, and the intervention had significant effect on axial elongation (coefficient, 0.09; 95% CI, 0.02-0.17;P = .01). Axial elongation was lower in the SMS group than in the control group during the intervention (0.27 mm [95% CI, 0.24-0.30] vs 0.31 mm [95% CI, 0.29-0.34];P = .03) and at year 2 (0.39 mm [95% CI, 0.35-0.42] vs 0.46 mm [95% CI, 0.42-0.50];P = .009) and year 3 (0.30 mm [95% CI, 0.27-0.33] vs 0.35 mm [95% CI, 0.33-0.37];P = .005) after the intervention. Myopic shift was lower in the SMS group than in the control group at year 2 (−0.69 diopters [D] [95% CI, −0.78 to −0.60] vs −0.82 D [95% CI, −0.91 to −0.73];P = .04) and year 3 (−0.47 D [95% CI, −0.54 to −0.39] vs −0.60 D [95% CI, −0.67 to −0.53];P = .01) after the intervention, as was myopia prevalence (year 2: 38.3% [51 of 133] vs 51.1% [68 of 133]; year 3: 46.6% [62 of 133] vs 65.4% [87 of 133]).Conclusions and RelevanceIn this randomized clinical trial, SMS text messages to parents resulted in lower axial elongation and myopia progression in schoolchildren over 3 years, possibly through increased outdoor time and light exposure, showing promise for reducing myopia prevalence.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR-IOC-17010525

Background Opaque bubble layer (OBL), which generates from photo-disruptive procedures on the cornea, has been a common phenomenon during femtosecond laser-assisted refractive surgeries and it would potentially impact eye tracking and flap lifting. And we have observed that an updated flap-making pattern could form less OBL clinically than the traditional pattern, which needed further approval. Thus, the purpose of this study is to prove our observation and investigate the possible risk factors related to the occurrence and type of OBL in laser in situ keratomileusis (LASIK) flaps using the Visumax laser system. Methods This prospective study included 167 eyes of 86 patients (mean age: 27.5 ± 6.1 years) undergoing bilateral femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for myopia/myopic astigmatism by the same surgeon from April 2020 to August 2020. Preoperative data on refraction, central corneal thickness (CCT), and keratometry as well as intraoperative data were included for analysis. A new flap-making pattern creating an offset between flap-cut and side-cut was adopted to compare with the traditional pattern. The operation video of flap formation was analyzed to identify the existence and type of OBL. The area covered by OBL and the ratio of OBL to flap were calculated using Image J software. Results Among 167 eyes, 54 eyes (32.3%) developed OBLs, consisting of 31 as hard OBL coexisting with soft OBL, and 23 as soft OBL alone. The OBL incidence was significantly reduced in eyes with the new flap-making pattern compared with the traditional pattern (13.8% vs. 52.5%, P < 0.001). Hard OBLs had larger area ratios than soft OBLs (14.3 ± 8.3% vs. 1.1 ± 1.8%, P < 0.001). Univariate analyses revealed that eyes with more myopia, thicker CCT, and traditional flap-making patterns were more likely to develop OBLs. Multivariate analysis further confirmed that more myopia, thicker CCT, and traditional flap-making pattern were risk factors for OBLs. A Larger corneal diameter was associated with a higher incidence of hard OBL when applying the traditional flap-making process. Conclusion More myopia, thicker CCT, and larger corneal diameter were risk factors for OBL development during flap creation, whereas a flap-making pattern with an offset between flap-cut and side-cut could reduce the incidence of OBL.