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Aims: To compare and rank the myopia control effects of different light wavelengths in children using a systematic review and Bayesian network meta-analysis (Bayesian NMA)., Methods: The review protocol was registered with PROSPERO. We searched PubMed, EMBASE and MEDLINE for relevant clinical and animal studies published as of 2 February 2023. We included studies comparing red, violet or full-spectrum light with controls. Data extracted included descriptive statistics and study outcomes (axial length (AL) elongation and progression of spherical equivalent (SE) refraction). After quality assessment, estimates of treatment effect outcomes (mean differences (MDs) and 95% CIs) were first pooled for the animal and clinical studies in a traditional meta-analysis. To compare and rank the different light wavelengths, the Bayesian NMA was then conducted for all the included clinical studies (12 studies) and separately for only randomised controlled trials (8 studies). MDs, 95% credible intervals (CrIs) and ranks of the various light wavelengths were estimated in the Bayesian NMA., Results: When all clinical studies were included in the Bayesian NMA (12 studies), only red-light significantly slowed AL elongation, MD (95% CrI), -0.38 mm (-0.59 mm to -0.16 mm)/year and SE refraction progression, 0.72D (0.35D to 1.10D)/year compared with controls. It remained the only significant intervention when effect sizes from only RCTs (eight studies) were separately combined, (-0.28 mm (-0.40 mm to -0.15 mm)/year and 0.57D (0.22D to 0.92D)/year, for AL and SE refraction, respectively)., Conclusion: Myopia control efficacy varied among different wavelengths of light, with red light ranked as the most effective., Prospero Registration Number: Clinical studies: CRD42022368998; animal studies: CRD42022368671., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To explore the prevalence and risk factors for myopia and uncorrected myopia in schoolchildren in southern China., Methods: The government-led Shantou Myopia Study was conducted from September 2020 to June 2021. Non-cycloplegic refraction was performed. Uncorrected visual acuity (UCVA) was measured along with presenting visual acuity if participants wore spectacles. Spherical equivalent refraction (SER) is defined as the spherical dioptres added to half of the cylindrical dioptres. Myopia is defined as SER <-0.50 dioptre with UCVA of <20/20 in at least one eye., Results: This study enrolled 724 828 schoolchildren (77.8% of all schoolchildren in Shantou) from 901 schools. Data from 721 032 schoolchildren (99.5%) were analysed (mean age 11.53±3.13 years, 6-20 years, 373 230 boys and 347 802 girls). Among them, 373 459 (51.8%) had myopia: 37.1% of 465 696 children in primary schools, 75.4% of 170 164 children in junior high schools and 84.8% of 85 172 children in senior high schools. The prevalence of myopia increases non-linearly with age. Older age, female and urban living environment were independently associated with myopia prevalence and myopic SER. Among the 373 459 children with myopia, 60.0% had no refractive correction: 74.9%, 53.9% and 35.5% in primary, junior high and senior high schools, respectively., Conclusion: The overall prevalence of myopia among schoolchildren in Shantou was 51.8%, higher than the national average in China. The proportion of uncorrected myopia is high, especially in primary schools. Our results indicate the need for public education on eye care among schoolchildren even in a municipal city., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown and has not been compared., Objective: To determine cost-effective options for controlling myopia progression in children., Design, Setting, and Participants: In this cost-effectiveness analysis, a Markov model was designed to compare the cost-effectiveness of interventions for controlling myopia progression over 5 years from a societal perspective in a simulated hypothetical cohort of patients aged 10 years with myopia. Myopia interventions considered included atropine eye drops, 0.05% and 0.01%, defocus incorporated multiple segment spectacles, outdoor activity, soft contact lenses (daily disposable and multifocal), rigid gas-permeable contact lenses, progressive addition lenses, bifocal spectacle lenses, orthokeratology, highly aspherical lenslets (HALs), and red light therapy; all interventions were compared with single-vision lenses. Deterministic and probabilistic sensitivity analysis determined the association of model uncertainties with the cost-effectiveness. Costs were obtained from the charges of the Hospital Authority of Hong Kong and The Chinese University of Hong Kong Eye Center., Main Outcome and Measures: The mean costs (in US dollars) per child included the cost of hospital visits, medications, and optical lenses. The outcomes of effectiveness were the annual spherical equivalent refraction (SER) and axial length (AL) reductions. Incremental cost-effectiveness ratios (ICERs) were calculated for each strategy relative to single-vision lenses over a time horizon of 5 years., Results: Outdoor activity, atropine (0.05%), red light therapy, HALs, and orthokeratology were cost-effective. The ICER of atropine, 0.05%, was US $220/SER reduction; red light therapy, US $846/SER reduction; and HALs, US $448/SER reduction. Outdoor activity yielded a savings of US $5/SER reduction and US $8/AL reduction. Orthokeratology resulted in an ICER of US $2376/AL reduction., Conclusions and Relevance: These findings suggest that atropine eye drops, 0.05%, and outdoor activity are cost-effective for controlling myopia progression in children. Though more expensive, red light therapy, HALs, and orthokeratology may also be cost-effective. The use of these interventions may help to control myopia in a cost-effective way.

Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional studies in PubMed, Embase, and Web of Science, and summarize the associated factors of myopic CNV using meta-analysis where applicable. Among 1,333 records assessed, 50 were found eligible, all having a low-to-moderate risk of bias. Highly myopic eyes with CNV had a higher risk of lacquer cracks (odds ratio = 2.88) and patchy chorioretinal atrophy (odds ratio = 3.43) than those without. The mean posterior staphyloma height (µm) was greater in myopic CNV eyes than in highly myopic eyes without CNV (mean difference = 82.03). The thinning of choroidal thickness (µm) between myopic eyes with and without CNV differed significantly (mean difference = -47.76). The level of vascular endothelial growth factor (pg/ml) in the aqueous humor of myopic CNV eyes was significantly higher than in highly myopic eyes without CNV (mean difference = 24.98), the same as interleukin-8 (IL-8) (pg/ml, mean difference = 7.73). Single-nucleotide polymorphisms in the vascular endothelial growth factor, complement factor I, and collagen type VIII alpha 1 genes were associated with myopic CNV. We found that myopic CNV eyes have a higher ratio of lacquer cracks and patchy chorioretinal atrophy, thinner choroid, greater posterior staphyloma height, and a higher level of vascular endothelial growth factor and IL-8 in aqueous. Structural predisposing lesions, hemodynamic, genetic, and systemic factors are also associated with myopic CNV., Competing Interests: Declaration of Competing Interest No conflicts of interest exist for any of the authors., (Copyright © 2023. Published by Elsevier Inc.)

The purpose of this study was to explore the findings from the Hong Kong Children Eye Study and the Low Concentration Atropine for Myopia Progression (LAMP-1) Study. The incidence of myopia among schoolchildren in Hong Kong more than doubled during the COVID-19 pandemic, with outdoor time decreased significantly and screen time increased. The change in lifestyle during the COVID-19 pandemic aggravated myopia development. Low-concentration atropine (0.05%, 0.025% and 0.01%) is effective in reducing myopia progression with a concentration-related response. This concentration-dependent response was maintained throughout a 3-year follow-up period, and all low concentrations were well tolerated. An age-dependent effect was observed in each treatment group with 0.05%, 0.025% and 0.01% atropine. Younger age was associated with a poor treatment response to low-concentration atropine. Additionally, low-concentration atropine induced choroidal thickening along a concentration-dependent response throughout the treatment period. During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. Stopping treatment at an older age and receiving lower concentration were associated with a smaller rebound effect. However, differences in the rebound effect were clinically small across all the three concentrations studied., (© 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Importance: Secondhand smoke (SHS) exposure potentially threatens ocular health; however, its association with myopia is unknown., Objective: To examine the association between SHS exposure and childhood myopia., Design, Setting, and Participants: Cross-sectional data from the population-based Hong Kong Children Eye Study were used. Data were collected from March 5, 2015, to September 12, 2021, at The Chinese University of Hong Kong Eye Center. Participants included children aged 6 to 8 years. Secondhand smoke exposure was evaluated using a validated questionnaire. All participants underwent comprehensive ophthalmic and physical examinations., Exposure: Secondhand smoke exposure., Main Outcomes and Measures: Generalized estimating equations were constructed to examine the association of SHS exposure with spherical equivalent and axial length; logistic regression models, with myopia rate; and linear regression models, with myopia onset., Results: A total of 12 630 children (mean [SD] age, 7.37 [0.88] years; 53.2% boys) were included in the analysis. Among the participants, 4092 (32.4%) had SHS exposure. After adjusting for age, sex, parental myopia, body mass index, near-work time, outdoor time, and family income, SHS exposure was associated with greater myopic refraction (β = -0.09 [95% CI, -0.14 to -0.03]) and longer axial length (β = 0.05 [95% CI, 0.02-0.08]). Children with SHS exposure were more likely to develop moderate (odds ratio [OR], 1.30 [95% CI, 1.06-1.59]) and high myopia (OR, 2.64 [95% CI, 1.48-4.69]). The association of SHS exposure with spherical equivalence and axial length was magnified in younger children. For each younger year of a child's exposure to SHS, SHS exposure was associated with a 0.07-D decrease in spherical equivalence (β = 0.07 [95% CI, 0.01-0.13]) and a 0.05-mm increase in axial length (β = -0.05 [95% CI, -0.08 to -0.01]). Exposure to SHS was associated with an earlier mean (SD) age at onset of myopia (72.8 [0.9] vs 74.6 [0.6] months; P = .01). Every increase in SHS exposure in units of 10 cigarettes per day was associated with greater myopic refraction (β = -0.07 [95% CI, -0.11 to -0.02]), axial length (β = 0.04 [95% CI, 0.01-0.06]), and likelihood of developing moderate (OR, 1.23 [95% CI, 1.05-1.44]) and high myopia (OR, 1.75 [95% CI, 1.20-2.56]), and earlier myopia onset (β = -1.30 [95% CI, -2.32 to -0.27])., Conclusions and Relevance: The findings of this cross-sectional study suggest that SHS exposure was associated with greater myopic refraction, longer axial length, greater likelihood of developing moderate and high myopia, and earlier myopia onset. The larger the quantity of SHS exposure and the younger the child, the more advanced myopia development and progression with which SHS exposure is associated.

Purpose: This study aimed to assess the prevalence and characteristics of the peripapillary gamma zone in myopic, emmetropic, and hyperopic eyes of Chinese children., Methods: Overall, 1274 children aged 6 to 8 years from the Hong Kong Children Eye Study underwent ocular examinations, including measurements of cycloplegic auto-refraction and axial length (AL). The optic disc was imaged using a Spectralis optical coherence tomography (OCT) unit and a protocol involving 24 equally spaced radial B-scans. The Bruch's membrane opening (BMO) was identified in over 48 meridians in each eye. The peripapillary gamma zone was defined as the region between the BMO and the border of the optic disc, identified by the OCT., Results: The prevalence of the peripapillary gamma zone was higher in myopic eyes (36.3%) than in emmetropic (16.1%) and hyperopic eyes (11.5%, P < 0.001). AL (per 1 mm; odds ratio [OR]) = 1.861, P < 0.001) and a more oval disc shape (OR = 3.144, P < 0.001) were associated with the presence of a peripapillary gamma zone after adjusting for demographic, systemic, and ocular variables. In the subgroup analysis, a longer AL was associated with the presence of a peripapillary gamma zone in myopic eyes (OR = 1.874, P < 0.001), but not in emmetropic (OR = 1.033, P = 0.913) or hyperopic eyes (OR = 1.044, P = 0.883). A peripapillary zone was not observed in the region nasal to the optic nerve in myopic eyes, in contrast to its presence in the same region in 1.9% of emmetropic eyes and 9.3% of hyperopic eyes; these intergroup differences were statistically significant (P < 0.001)., Conclusions: Although peripapillary gamma zones were observed in the eyes of both myopic and non-myopic children, their characteristics and distribution patterns were substantially different.

Background: To compare the prevalence of refractive (RA), corneal (CA), and internal astigmatism (IA) in Hong Kong children and adults and evaluate the role of IA in compensating for total astigmatism and its relations to myopic traits., Methods: The Hong Kong Children Eye Study is a population-based cross-sectional study. Totally 3704 school children (mean age 7.5 ± 1.0 years) and 5577 adults (mean age 41.1 ± 7.5 years), who were their parents, were recruited. Cycloplegic and non-cycloplegic refractive cylinders were obtained from children and adults, respectively. Spearman correlation was applied to detect associations between astigmatism, ocular biometrics, refraction, and lens power. Astigmatism compensation factor (CF) was derived from the power vector analysis J0 and J45., Results: The prevalence of RA (≤-1.0 D), CA (≥+1.0 D) and IA (≥+1.0 D) was 21.9%, 63.9%, and 9.9% in children, and 30.9%, 39.5%, and 23.7% in adults respectively. The mean RA, CA and IA values in children and adults were -0.69 ± 0.66 D, +1.14 ± 0.61 D, +0.62 ± 0.32 D, and -0.80 ± 0.74 D, +0.97 ± 0.69 D, and +0.76 ± 0.43 D, respectively. In adults and children, IA was negatively correlated with axial length (p < 0.0001), but positively correlated with spherical values and equivalent (p < 0.0001), suggesting an association of astigmatism with myopic traits. A greater proportion of children exhibited compensation by IA than adults in J0 (86.6% vs. 66.0%, p < 0.0001) and J45 components (55.5% vs. 41.7%, p < 0.0001)., Conclusions: Chinese children in Hong Kong exhibit a higher prevalence of RA and CA than in other cities. Children displayed a greater compensation by IA than adults, suggesting an age-related attenuation of IA compensation. IA is associated with myopic traits., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Importance: Childhood myopia increased during the COVID-19 pandemic. Limited evidence exists about whether myopia development was reversed or worsened after the lockdown., Objective: To determine the prevalence of myopia and its associated factors before, during, and after COVID-19 restrictions., Design, Setting, and Participants: This population-based, repeated cross-sectional study evaluated children aged 6 to 8 years from the Hong Kong Children Eye Study between 2015 and 2021 in 3 cohorts: before COVID-19 (2015-2019), during COVID-19 restrictions (2020), and after COVID-19 restrictions were lifted (2021)., Exposures: All the children received ocular examinations, including cycloplegic autorefraction and axial length. Data about the children's lifestyle, including time spent outdoors, near-work time, and screen time, were collected from a standardized questionnaire., Main Outcomes and Measures: The main outcomes were the prevalence of myopia, mean spherical equivalent refraction, axial length, changes in lifestyle, and the associated factors over 7 years. Data were analyzed using descriptive statistics, logistic regression, and generalized estimating equations., Results: Of 20 527 children (mean [SD] age, 7.33 [0.89] years; 52.8% boys and 47.2% girls), myopia prevalence was stable from 2015 to 2019 (23.5%-24.9%; P = .90) but increased to 28.8% (P < .001) in 2020 and 36.2% (P < .001) in 2021. The mean (SD) time spent outdoors was much lower in 2020 (0.85 [0.53] h/d; P < .001) and 2021 (1.26 [0.48] h/d; P < .001) compared with pre-COVID-19 levels (1.40 [0.47]-1.46 [0.65] h/d). The trend was reversed for total near-work time and screen time. High myopia prevalence was associated with the COVID-19 pandemic (odds ratio [OR], 1.40; 95% CI, 1.28-1.54; P < .001), younger age (OR, 1.84; 95% CI, 1.76-1.93; P < .001), male sex (OR, 1.11; 95% CI, 1.03-1.21; P = .007), lower family income (OR, 1.05; 95% CI, 1.00-1.09; P = .04), and parental myopia (OR, 1.61; 95% CI, 1.52-1.70; P < .001). During the pandemic, mean (SD) near-work and screen times in children from lower-income families were 5.16 (2.05) h/d and 3.44 (1.97) h/d, more than from higher-income families (4.83 [1.85] and 2.90 [1.61] h/d, respectively)., Conclusions and Relevance: The findings of this cross-sectional study revealed that after COVID-19 restrictions were lifted in Hong Kong, myopia prevalence among children was higher than before the pandemic, and lifestyle did not return to pre-COVID-19 levels. Younger children and those from low-income families were at a higher risk of myopia development during the pandemic, suggesting that collective efforts for myopia control should be advocated for these groups.

The rising prevalence of myopia is a major global public health concern. Economic evaluation of myopia interventions is critical for maximizing the benefits of treatment and the healthcare system. This systematic review aimed to evaluate the cost-effectiveness of interventions for treating myopia. Five databases were searched - Embase, Emcare, PubMed, Web of Science, and ProQuest - from inception to July 2022 and a total of 2,099 articles were identified. After careful assessments, 6 studies met the eligibility criteria. The primary outcomes of this systematic review were costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). The secondary outcomes included utility values and net monetary benefits (NMB). One study determined the cost-effectiveness of photorefractive screening plus treatment with 0.01% atropine, 2 studies examined cost-effectiveness of corneal refractive surgery, and 3 studies evaluated cost-effectiveness of commonly used therapies for pathologic myopia. Corneal refractive surgeries included laser in situ keratomileusis (LASIK), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), photorefractive keratectomy (PRK), and small-incision lenticule extraction (SMILE). Interventions for pathologic myopia included ranibizumab, conbercept, and photodynamic therapy (PDT). At an incremental cost of NZ$ 18 (95% CI 15, 20) (US$ 11) per person, photorefractive screening plus 0.01% atropine resulted in an ICER of NZ$ 1,590/QALY (US$ 1,001/QALY) (95% CI NZ$ 1,390, 1,791) for an incremental QALY of 0.0129 (95% CI 0.0127, 0.0131). The cost of refractive surgery in Europe ranged from €3,075 to €3,123 ([US$4,046 to $4,109 - adjusted to 2021 inflation). QALYs associated with these procedures were 23 (FS-LASIK) and 24 (SMILE and PRK) with utility values of 0.8 and ICERs ranging from approximately €14 (US$17)/QALY to €19 (US$23)/QALY. The ICER of LASIK was US$683/diopter gained (inflation-adjusted). The ICER of ranibizumab and PDT were £8,778 (US$12,032)/QALY and US$322,460/QALY respectively, with conbercept yielding a saving of 541,974 RMB (US$80,163)/QALY, respectively. The use of 0.01% atropine and corneal refractive surgery were cost-effective for treating myopia. Treating pathologic myopia with ranibizumab and conbercept were more cost-effective than PDT. Prevention of myopia progression is more cost-effective than treating pathologic myopia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Agyekum, Chan, Zhang, Huo, Yip, Ip, Tham, Chen, Zhang, Pang and Yam.)

Importance: Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed., Objective: To evaluate the efficacy of low-concentration atropine eyedrops at 0.05% and 0.01% concentration for delaying the onset of myopia., Design, Setting, and Participants: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than -1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022., Interventions: Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years., Main Outcomes and Measures: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least -0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D)., Results: Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% [95% CI, 12.0%-36.4%]) and percentage of patients with fast myopic shift (difference, 28.9% [95% CI, 16.5%-40.5%]). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% [95% CI, 5.2%-29.2%]) and percentage of patients with fast myopic shift (difference, 20.1% [95% CI, 8.0%-31.6%]). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year., Conclusions and Relevance: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety., Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-15006883.

Background: The impacts of social restrictions for COVID-19 on children's vision and lifestyle remain unknown., Aims: To investigate myopia incidence, spherical equivalent refraction (SER) and lifestyle changes among schoolchildren during the COVID-19 pandemic., Methods: Two separate longitudinal cohorts of children aged 6-8 years in Hong Kong were included. The COVID-19 cohort was recruited at the beginning of the COVID-19 outbreak, whereas the pre-COVID-19 cohort was recruited before the COVID-19 pandemic. All children received ocular examinations, and answered a standardised questionnaire relating to their lifestyle, including time spent on outdoor activities and near work, both at baseline and at follow-up visits., Results: A total of 1793 subjects were recruited, of whom 709 children comprised the COVID-19 cohort with 7.89±2.30 months of follow-up, and 1084 children comprised the pre-COVID-19 cohort with 37.54±3.12 months of follow-up. The overall incidence was 19.44% in the COVID-19 cohort, and 36.57% in pre-COVID-19 cohort. During the COVID-19 pandemic, the change in SER and axial length was -0.50±0.51 D and 0.29±0.35 mm, respectively; the time spent on outdoor activities decreased from 1.27±1.12 to 0.41±0.90 hours/day (p<0.001), while screen time increased from 2.45±2.32 to 6.89±4.42 hours/day (p<0.001)., Conclusions: We showed a potential increase in myopia incidence, significant decrease in outdoor time and increase in screen time among schoolchildren in Hong Kong during the COVID-19 pandemic. Our results serve to warn eye care professionals, and also policy makers, educators and parents, that collective efforts are needed to prevent childhood myopia-a potential public health crisis as a result of COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To examine the association between near work, screen time including TV and outdoor time with myopia in children from the Sunflower Myopia Asian Eye Epidemiology Consortium (AEEC)., Methods: We analysed AEEC cross-sectional data (12 241 children) on risk factors (near work, screen time including TV and outdoor time) and myopia of six population-based studies (China, Hong Kong and Singapore). Cycloplegic refraction and axial length (AL) measurements were included. Risk factors were determined using questionnaires. Data were pooled from each study, and multivariable regression analysis was performed to evaluate the associations between risks factors and myopia, spherical equivalent (SE) and AL., Results: Among the included children, 52.1% were boys, 98.1% were Chinese and 69.7% lived in urban areas. Mean±standard deviation (SD) for age was 8.8 ± 2.9 years, for SE was -0.14 ± 1.8 D and for AL was 23.3 ± 1.1 mm. Myopia prevalence was 30.6%. In multivariate analysis, more reading and writing (OR = 1.17; 95% CI, 1.11-1.24), more total near work (OR = 1.05; 95% CI, 1.02-1.09) and less outdoor time (OR = 0.82, 95% CI, 0.75-0.88) were associated with myopia (p's < 0.05). These factors were similarly associated with SE and AL (p's < 0.05), except for total near work and AL (p = 0.15). Screen time including TV was not significantly associated with myopia (p = 0.49), SE (p = 0.49) or AL (p = 0.83)., Conclusion: In this study, increased reading and writing and decreased outdoor time were associated with myopia. Screen time may be a surrogate factor of near work or outdoor time, but further research is needed to assess its role as an independent risk factor for myopia., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate longitudinal changes in subfoveal choroidal thickness (SFChT) among children receiving atropine 0.05%, 0.025%, or 0.01% over 2 years and their associations with treatment outcomes in myopia control., Design: Double-blinded randomized controlled trial., Methods: SFChT was measured at 4-month intervals using spectral domain optical coherence tomography. Cycloplegic spherical equivalent (SE), axial length (AL), best-corrected visual acuity, parental SE, outdoor time, near work diopter hours, and treatment compliance were also measured., Results: 314 children were included with qualified choroidal data. The 2-year changes in SFChT from baseline were 21.15 ± 32.99 µm, 3.34 ± 25.30 µm, and -0.30 ± 27.15 µm for the atropine 0.05%, 0.025%, and 0.01% groups, respectively (P < .001). A concentration-dependent response was observed, with thicker choroids at higher atropine concentrations (β = 0.89, P < .001). Mean SFChT thickness significantly increased at 4 months in the atropine 0.025% (P = .001) and 0.05% groups (P < .001) and then remained stable until the end of the second year (P > .05 for all groups). Over 2 years, an increase in SFChT was associated with slower SE progression (β = 0.074, P < .001) and reduced AL elongation (β = -0.045, P < .001). In the mediation analysis, 18.45% of the effect on SE progression from atropine 0.05% was mediated via its choroidal thickening., Conclusions: Low concentration atropine induced a choroidal thickening effect along a concentration-dependent response throughout the treatment period. The choroidal thickening was associated with a slower SE progression and AL elongation among all the treatment groups. Choroidal response can be used for assessment of long-term treatment outcomes and as a guide for concentration titrations of atropine., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The contributory roles of vitamin D in ocular and visual health have long been discussed, with numerous studies pointing to the adverse effects of vitamin D deficiency. In this paper, we provide a systematic review of recent findings on the association between vitamin D and different ocular diseases, including myopia, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), dry eye syndrome (DES), thyroid eye disease (TED), uveitis, retinoblastoma (RB), cataract, and others, from epidemiological, clinical and basic studies, and briefly discuss vitamin D metabolism in the eye. We searched two research databases for articles examining the association between vitamin D deficiency and different ocular diseases. One hundred and sixty-two studies were found. There is evidence on the association between vitamin D and myopia, AMD, DR, and DES. Overall, 17 out of 27 studies reported an association between vitamin D and AMD, while 48 out of 54 studies reported that vitamin D was associated with DR, and 25 out of 27 studies reported an association between vitamin D and DES. However, the available evidence for the association with other ocular diseases, such as glaucoma, TED, and RB, remains limited.

Aims: To assess the association of single-nucleotide polymorphisms (SNPs) with myopia progression for polygenic risk prediction in children., Methods: Six SNPs ( ZC3H11B rs4373767, ZFHX1B rs13382811, KCNQ5 rs7744813, MET rs2073560, SNTB1 rs7839488 and GJD2 rs524952) were analysed in 1043 school children, who completed 3-year follow-up, using TaqMan genotyping assays. SNP associations with progression in spherical equivalent (SE) were analysed by logistic regression. Polygenic risk scores (PRS) were applied for computing the sum of the risk alleles of multiple SNPs corresponding to myopia progression, weighted by the effect sizes of corresponding SNPs., Results: GJD2 rs524952 showed significant association with fast progression (OR=1.32, 95% CI 1.10 to 1.59; p=0.003) and KCNQ5 rs7744813 had nominal association (OR=1.32, 95% CI 1.04 to 1.67; p=0.02). In quantitative traits locus analysis, GJD2 rs524952 and KCNQ5 rs7744813 were associated with progression in SE (β=-0.038 D/year, p=0.008 and β=-0.042 D/year, p=0.02) and axial elongation (β=0.016 mm/year, p=0.01 and β=0.017 mm/year, p=0.027). ZFHX1B rs13382811 also showed nominal association with faster progression in SE (β=-0.041 D/year, p=0.02). PRS analysis showed that children with the highest PRS defined by rs13382811, rs7744813 and rs524952 had a 2.26-fold of increased risk of fast myopia progression (p=4.61×10 -5 ). PRS was also significantly associated with SE progression (R 2 =1.6%, p=3.15×10 -5 ) and axial elongation (R 2 =1.2%, p=2.6×10 -4 )., Conclusions: In this study, multi-tiered evidence suggested SNPs in ZFHX1B , KCNQ5 and GJD2 as risk factors for myopia progression in children. Additional attention and appropriate interventions should be given for myopic children with high-risk PRS as defined by GJD2 rs524952, KCNQ5 rs7744813 and ZFHX1B rs13382811., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the associations of multiple single-nucleotide polymorphisms (SNPs) with the severities and endophenotypes of myopia in children., Methods: A total of 3300 children aged 5-10 years were recruited: 137 moderate and high myopia (SE≤-3.0D), 670 mild myopia (-3.0D-0.5D). 13 SNPs in 13 genes/loci were selected for genotyping in all subjects using TaqMan assays. Associations between each SNP with myopia severities and ocular traits (spherical equivalent (SE), axial length (AL) and corneal radius (CR)) were analysed., Results: When compared with controls, SNPs ZC3H11B rs4373767 (OR=1.15, p=0.038), BICC1 rs7084402 (OR=1.18, p=0.005) and GJD2 rs524952 (OR=1.14, p=0.025) showed nominal associations with overall myopia. ZC3H11B rs4373767 and BICC1 rs7084402 showed stronger associations with moderate and high myopia (rs4373767: OR=1.42, p=0.018; rs7084402: OR=1.33, p=0.025), while GJD2 rs524952 had a stronger association with mild myopia (OR=1.14, p=0.025). GJD2 rs524952 also showed a difference between emmetropia and hyperopia (p=0.018). In quantitative trait locus analysis, ZC3H11B rs4373767, KCNQ5 rs7744813 and GJD2 rs524952 were correlated with both myopic SE (β=-0.09, p=0.03; β=-0.12, p=0.007; β=-0.13, p=0.0006, respectively) and AL (β=0.07, p=0.002; β=0.09, p=0.0008; β=0.07, p=0.0003, respectively). SNTB1 rs7839488 was correlated with both AL (β=0.07, p=0.005) and CR (β=0.02, p=0.006). Moreover, ZC3H11B rs4373767-T (β=0.006; p=0.018), KCNQ5 rs7744813-A (β=0.007; p=0.015) and GJD2 rs524952-T (β=0.009; p=0.0006) were correlated with AL-CR ratio., Conclusions and Relevance: ZC3H11B and BICC1 are genetic risk factors for moderate and high myopia, while ZC3H11B, KCNQ5, SNTB1 and GJD2 confer risk to excessive AL in children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate changes in ocular biometrics in groups receiving 0.05%, 0.025%, and 0.01% atropine compared with placebo over 1 year based on the Low-Concentration Atropine for Myopia Progression (LAMP) study., Design: Double-blinded, randomized, placebo-controlled trial., Participants: Three hundred eighty-three children aged 4 to 12 years who were assigned randomly to receive 0.05%, 0.025%, 0.01% atropine, or placebo once daily in both eyes and completed the first year of the LAMP study., Methods: Cycloplegic spherical equivalent (SE), axial length (AL), corneal curvature (K), and anterior chamber depth (ACD) were measured by IOLMaster. Corneal astigmatism and lens power were calculated. The ocular biometric parameter changes were compared among groups. Contributions to SE progression from ocular parameters were determined and compared among groups., Main Outcome Measures: Changes in ocular biometrics and their associations with the changes in SE., Results: Over 1 year, changes in AL were 0.20 ± 0.25 mm, 0.29 ± 0.20 mm, 0.36 ± 0.29 mm, and 0.41 ± 0.22 mm in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P < 0.001), with a concentration-dependent response. Corneal power remained stable, and its changes were similar across all atropine concentrations: -0.02 ± 0.14 diopter (D), -0.01 ± 0.14 D, -0.01 ± 0.12 D, and 0.01 ± 0.14 D in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P = 0.10). Lens power decreased over time in each concentration, but its changes also were similar across all concentrations: -0.31 ± 0.43 D, -0.38 ± 0.47 D, -0.40 ± 0.43 D, and -0.41 ± 0.43 D in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P = 0.24). Changes in ACD remained similar across all concentrations (P = 0.41). The contributions to SE progression from the ocular biometric changes after adjusting for age and gender in each concentration were similar across all groups (P > 0.05)., Conclusions: Low-concentrations of atropine (0.05%, 0.025%, and 0.01%) have no clinical effect on corneal or lens power. Antimyopic effects of low-concentration atropine act mainly on reducing AL elongation, and therefore could reduce the risk of subsequent myopia complications., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the effects on childhood myopia of parental myopia, parental education, children's outdoor time, and children's near work., Design: Population-based cross-sectional study., Methods: A total of 6,155 subjects in 2,055 family trios (1 child and both parents). Cycloplegic autorefraction was measured for children and noncycloplegic autorefraction for parents. Parental education, children's outdoor time, and near work were collected by questionnaires. Children were categorized into 10 groups based on parental myopia levels. Associations of the above factors with myopia were evaluated by regression analyses. The areas under the receiver operating characteristic curve (AUROCs) for myopia were evaluated., Results: Mild parental myopia did not increase childhood myopia's risk, but the risk was 11.22-folds when both parents were highly myopic. Higher parental education (Father: OR 1.08, P = .046; Mother: OR 1.11, P = .001) and more reading time of children were risk factors (OR 1.21, P = .044). Reduced odds of myopia were associated with more time spent on outdoor activities (OR 0.78, P = .017). Notably, all these factors became insignificant after adjustment, except for parental myopia. Children with more severe parental myopia spent more time on reading, but less on electronic devices. Parental myopic status alone accounted for 11.82% of myopia variation in children. With age and parental myopia, the AUROC for myopia was 0.731., Conclusions: Among parental and environmental factors, parental myopia confers, in a dose-related manner, the strongest independent effect on childhood myopia. Therefore children with high risk of myopia can be identified for early prevention, based on parental myopia data., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate the associations of single-nucleotide polymorphisms (SNPs) in the ZC3H11B, ZFHX1B, VIPR2 , SNTB1 and MIPEP genes with severities of myopia in Chinese populations., Methods: Based on previous myopia genome-wide association studies, five SNPs ( ZC3H11B rs4373767, ZFHX1B rs13382811, VIPR2 rs2730260, SNTB1 rs7839488 and MIPEP rs9318086) were selected for genotyping in a Chinese cohort of 2079 subjects: 252 extreme myopia, 277 high myopia, 393 moderate myopia, 366 mild myopia and 791 non-myopic controls. Genotyping was performed by TaqMan assays. Allelic frequencies of the SNPs were compared with myopia severities and ophthalmic biometric measurements., Results: The risk allele T of ZC3H11B SNP rs4373767 was significantly associated with high myopia (OR=1.39, p=0.007) and extreme myopia (OR=1.34, p=0.013) when compared with controls, whereas ZFHX1B rs13382811 (allele T, OR=1.33, p=0.018) and SNTB1 rs7839488 (allele G, OR=1.71, p=8.44E-05) were significantly associated with extreme myopia only. In contrast, there was no significant association of these SNPs with moderate or mild myopia. When compared with mild myopia, subjects carrying T allele of rs4373767 had a risk of progressing to high myopia (spherical equivalent ≤-6 dioptres) (OR=1.29, p=0.017). Similarly, the T allele of rs13382811 also imposed a significant risk to high myopia (OR=1.36, p=0.007). In quantitative traits analysis, SNPs rs4373767, rs13382811 and rs7839488 were correlated with axial length and refractive errors., Conclusions: We confirmed ZC3H11B as a susceptibility gene for high and extreme myopia, and ZFHX1B and SNTB for extreme myopia in Chinese populations. Instead of myopia onset, these three genes were more likely to impose risks of progressing to high and extreme myopia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the association between single-nucleotide polymorphisms (SNPs) in the ZC3H11B, RSPO1, C3orf26, GJD2, ZNRF3, and WNT7B genes and myopia endophenotypes in children., Methods: Seven SNPs identified in previous genome-wide association studies of axial length (AL) were genotyped in 2883 Southern Han Chinese children. Multiple linear regression analyses were conducted to evaluate the genotype association with AL, spherical equivalent (SE), corneal curvature (CC), and central corneal thickness (CCT)., Results: Two SNPs-namely, rs12144790 in RSPO1 (allele T, P = 0.0066, β = 0.062) and rs10453441 in WNT7B (allele A, P = 8.03 × 10-6, β = 0.103)-were significantly associated with AL. The association of rs4373767 in ZC3H11B (allele C, P = 0.030, β = -0.053) could not withstand the correction for multiple testing. WNT7B rs10453441 showed a strong association with CC (P = 1.17 × 10-14, β = 0.053) and with CCT (P = 0.0026, β = 2.65). None of the tested SNPs was significantly associated with SE. The C allele of SNP rs12321 in ZNRF3 was associated with CC (P = 0.0060, β = -0.018)., Conclusions: This study revealed that the RSPO1 SNP rs12144790 was associated with AL, whereas WNT7B rs10453441 was associated with AL, CC, and CCT in children. A novel association between ZNRF3 rs12321 and CC was discovered. Our data suggest that the RSPO1 and WNT7B genes might exert their effects on multiple aspects of eye growth during childhood. Potential differences in the genetic profiles of AL between children and adults should be explored in larger cohorts.

Purpose: Low-concentration atropine is an emerging therapy for myopia progression, but its efficacy and optimal concentration remain uncertain. Our study aimed to evaluate the efficacy and safety of low-concentration atropine eye drops at 0.05%, 0.025%, and 0.01% compared with placebo over a 1-year period., Design: Randomized, placebo-controlled, double-masked trial., Participants: A total of 438 children aged 4 to 12 years with myopia of at least -1.0 diopter (D) and astigmatism of -2.5 D or less., Methods: Participants were randomly assigned in a 1:1:1:1 ratio to receive 0.05%, 0.025%, and 0.01% atropine eye drops, or placebo eye drop, respectively, once nightly to both eyes for 1 year. Cycloplegic refraction, axial length (AL), accommodation amplitude, pupil diameter, and best-corrected visual acuity were measured at baseline, 2 weeks, 4 months, 8 months, and 12 months. Visual Function Questionnaire was administered at the 1-year visit., Main Outcome Measures: Changes in spherical equivalent (SE) and AL were measured, and their differences among groups were compared using generalized estimating equation., Results: After 1 year, the mean SE change was -0.27±0.61 D, -0.46±0.45 D, -0.59±0.61 D, and -0.81±0.53 D in the 0.05%, 0.025%, and 0.01% atropine groups, and placebo groups, respectively (P < 0.001), with a respective mean increase in AL of 0.20±0.25 mm, 0.29±0.20 mm, 0.36±0.29 mm, and 0.41±0.22 mm (P < 0.001). The accommodation amplitude was reduced by 1.98±2.82 D, 1.61±2.61 D, 0.26±3.04 D, and 0.32±2.91 D, respectively (P < 0.001). The pupil sizes under photopic and mesopic conditions were increased respectively by 1.03±1.02 mm and 0.58±0.63 mm in the 0.05% atropine group, 0.76±0.90 mm and 0.43±0.61 mm in the 0.025% atropine group, 0.49±0.80 mm and 0.23±0.46 mm in the 0.01% atropine group, and 0.13±1.07 mm and 0.02±0.55 mm in the placebo group (P < 0.001). Visual acuity and vision-related quality of life were not affected in each group., Conclusions: The 0.05%, 0.025%, and 0.01% atropine eye drops reduced myopia progression along a concentration-dependent response. All concentrations were well tolerated without an adverse effect on vision-related quality of life. Of the 3 concentrations used, 0.05% atropine was most effective in controlling SE progression and AL elongation over a period of 1 year., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To conduct a systematic review and meta-analysis of the association of blood vitamin D (25-hydroxyvitamin D, 25(OH)D) concentration and vitamin D pathway genes with myopia., Methods: We searched the MEDLINE and EMBASE databases for studies published up to 29 January 2018. Cross-sectional or cohort studies which evaluated the blood 25(OH)D concentration, blood 25(OH)D3 concentration or vitamin D pathway genes, in relation to risk of myopia or refractive errors were included. Standard mean difference (SMD) of blood 25(OH)D concentrations between the myopia and non-myopia groups was calculated. The associations of blood 25(OH)D concentrations and polymorphisms in vitamin D pathway genes with myopia using summary ORs were evaluated., Results: We summarised seven studies involving 25 008 individuals in the meta-analysis. The myopia group had lower 25(OH)D concentration than the non-myopia group (SMD=-0.27 nmol/L, p=0.001). In the full analysis, the risk of myopia was inversely associated with blood 25(OH)D concentration after adjusting for sunlight exposure or time spent outdoors (adjusted odds ratio (AOR)=0.92 per 10 nmol/L, p<0.0001). However, the association was not statistically significant for the <18 years subgroup (AOR=0.91 per 10 nmol/L, p=0.13) and was significant only for 25(OH)D3 (likely to be mainly sunlight derived), but not total 25(OH)D (AOR=0.93 per 10 nmol/L, p=0.00007; AOR=0.91 per 10 nmol/L, p=0.15). We analysed four single nucleotide polymorphisms in the VDR gene from two studies; there was no significant association with myopia., Conclusions: Lower 25(OH)D is associated with increased risk of myopia; the lack of a genetic association suggests that 25(OH)D level may be acting as a proxy for time outdoors., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: To investigate the association of the paired box gene 6 ( PAX6 ) with different severities of myopia., Methods: A total of four haplotype-tagging single-nucleotide polymorphisms (SNPs; rs2071754, rs3026354, rs3026390 and rs628224) and two previously reported SNPs (rs644242 and rs662702) in the PAX6 gene were analysed in a Hong Kong Chinese cohort of 1288 myopia subjects (including 252 extreme myopia, 277 high myopia, 393 moderate myopia and 366 mild myopia) and 791 no myopia controls. Allelic association analyses were performed for individual SNPs in different subgroups of myopia and in combined myopia, followed by a meta-analysis of our current data with reported data on PAX6 in myopia., Results: The association of tagging SNPs rs2071754 and rs644242 with extreme myopia could not withstand multiple correction (rs2071754: OR=1.25, P value=0.031; rs644242: OR=1.33, P value=0.032). In the meta-analysis, rs644242 showed an enhanced, significant association with extreme myopia (OR=1.27, 95% CI 1.10 to 1.46, P value=0.001; I 2 =0%). In contrast, there was no significant association between the PAX6 SNPs and high, moderate or mild myopia. No linear correlation was found between the PAX6 SNPs and axial length., Conclusion: This study provides additional evidence suggesting that the PAX6 SNP rs644242 is associated with extreme myopia but not lower grade myopia. Thus, PAX6 may be implicated in the development or progression into severe myopia. Further longitudinal studies are warranted., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Myopia is a major cause of visual impairment worldwide. In particular, high myopia is associated with serious blinding complications, including retinal detachment, chorioretinal degeneration, and choroidal neovascularization. Myopia is multifactorial in etiology, resulting from the interaction of environmental and genetic risk factors. During the past 2 decades, a large number of gene loci and variants have been identified for myopia. There are more than 20 myopia-associated loci spanning all chromosomes. Earlier findings were obtained mainly from family linkage analyses and candidate gene studies, and more recent results are principally from genome-wide association studies and exome sequencing. Some genetic associations have been successfully validated and replicated in populations of different geographic localities and ethnicities, but some have not. Compared with Whites, Asian populations-in particular Japanese, Korean, and Chinese-have a much higher prevalence of myopia, especially high myopia. Both genetic and environmental factors contribute to such ethnic variations. This review attempts to summarize and compare the allelic frequencies of gene variants known to be associated with myopia in different ethnic groups, especially in the Asia-Pacific region.

Severe myopia (defined as spherical equivalent < -6.0 D) is a predominant problem in Asian countries, resulting in substantial morbidity. We performed a meta-analysis of four genome-wide association studies (GWAS), all of East Asian descent totaling 1603 cases and 3427 controls. Two single nucleotide polymorphisms (SNPs) (rs13382811 from ZFHX1B [encoding for ZEB2] and rs6469937 from SNTB1) showed highly suggestive evidence of association with disease (P < 1 × 10(-7)) and were brought forward for replication analysis in a further 1241 severe myopia cases and 3559 controls from a further three independent sample collections. Significant evidence of replication was observed, and both SNP markers surpassed the formal threshold for genome-wide significance upon meta-analysis of both discovery and replication stages (P = 5.79 × 10(-10), per-allele odds ratio (OR) = 1.26 for rs13382811 and P = 2.01 × 10(-9), per-allele OR = 0.79 for rs6469937). The observation at SNTB1 is confirmatory of a very recent GWAS on severe myopia. Both genes were expressed in the human retina, sclera, as well as the retinal pigmented epithelium. In an experimental mouse model for myopia, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for Zfhx1b and Sntb1. These new data advance our understanding of the molecular pathogenesis of severe myopia.

Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

Myopia is the most common eye condition leading to visual impairment and is greatly influenced by genetics. Over the last two decades, more than 400 associated gene loci have been mapped for myopia and refractive errors via family linkage analyses, candidate gene studies, genome-wide association studies (GWAS), and next-generation sequencing (NGS). Lifestyle factors, such as excessive near work and short outdoor time, are the primary external factors affecting myopia onset and progression. Notably, besides becoming a global health issue, myopia is more prevalent and severe among East Asians than among Caucasians, especially individuals of Chinese, Japanese, and Korean ancestry. Myopia, especially high myopia, can be serious in consequences. The etiology of high myopia is complex. Prediction for progression of myopia to high myopia can help with prevention and early interventions. Prediction models are thus warranted for risk stratification. There have been vigorous investigations on molecular genetics and lifestyle factors to establish polygenic risk estimations for myopia. However, genes causing myopia have to be identified in order to shed light on pathogenesis and pathway mechanisms. This report aims to examine current evidence regarding (1) the genetic architecture of myopia; (2) currently associated myopia loci identified from the OMIM database, genetic association studies, and NGS studies; (3) gene-environment interactions; and (4) the prediction of myopia via polygenic risk scores (PRSs). The report also discusses various perspectives on myopia genetics and heredity. [ABSTRACT FROM AUTHOR]

Purpose: To determine the myopia prevalence in Hong Kong Chinese children and their parents. Methods: It was a population‐based cross‐sectional study. A total of 4257 children aged 6–8 years, and 5880 parents were recruited in the Hong Kong Children Eye Study. Cycloplegic autorefraction was measured for children; and non‐cycloplegic autorefraction for parents. Parental educational level, children's outdoor time, and near work were collected by validated questionnaires. Results: In children aged 6–8 years, 25.0% were myopic, and among them, 12.7% for the 6‐year‐olds, 24.4% for the 7‐year‐olds and 36.1% for the 8‐year‐old. About 0.7% of children aged 8 years were high myopia. In all age groups, boys (their myopia rate: 13.9% at 6 years, 26.7% at 7 years, and 38.3% at 8 years) were more myopic than girls (11.3% at 6 years, 22.0% at 7 years, 33.4% at 8 years). Among parents, 72.2% were myopic (mother, 73.2%; father, 70.7%) and 13.5% high myopia (mother, 12.8%; father, 14.5%). It was observed that prevalence decreased with ages and increased with education level. Conclusion: There is a strikingly high prevalence of myopia in Hong Kong children aged 6–8, much higher than that of other regions of China. Of note, the prevalence of children was similar to that in 15 years ago. Furthermore, the myopia prevalence of parents is high, and it had already increased in this cohort. Prevention of childhood myopia is important, likewise for visual complications from high myopia in adults. [ABSTRACT FROM AUTHOR]

Associations between corneal biomechanics, axial elongation and myopia are important but previous results are conflicting. Our population-based study aimed to investigate factors associated with corneal biomechanics, and their relationships with myopia in children and adults. Data from 3643 children and 1994 parents showed that children had smaller deformation amplitudes (DA) than parents (p < 0.001). A larger DA was significantly associated with elongated axial length (AL; children: ß = 0.011; adults: ß = 0.0013), higher corneal curvature (children: ß = 0.0086; adults: ß = 0.0096), older age (children: ß = 0.010; adults: ß = 0.0013), and lower intraocular pressure (IOP; children: ß = −0.029; adults: ß = −0.031) in both cohorts. The coefficient of age for DA in children was larger than in adults (p < 0.001), indicating that the DA change with age in children is faster than in adults. DA was significantly associated with spherical equivalent (p < 0.001) resulting from its correlation with AL and corneal curvature. In conclusion, the cornea is more deformable in adults than in children, whereas corneal deformation amplitude increases faster with age in children than that in adults, along with AL elongation. Longer AL, steeper corneal curvature, older age and smaller IOP correspond to a more deformable cornea. The association between corneal deformation amplitude and refraction was mediated via AL and corneal curvature. [ABSTRACT FROM AUTHOR]

To evaluate (1) the long-term efficacy of low-concentration atropine over 5 years, (2) the proportion of children requiring re-treatment and associated factors, and (3) the efficacy of pro re nata (PRN) re-treatment using 0.05% atropine from years 3 to 5. Randomized, double-masked extended trial. Children 4 to 12 years of age originally from the Low-Concentration Atropine for Myopia Progression (LAMP) study. Children 4 to 12 years of age originally from the LAMP study were followed up for 5 years. During the third year, children in each group originally receiving 0.05%, 0.025%, and 0.01% atropine were randomized to continued treatment and treatment cessation. During years 4 and 5, all continued treatment subgroups were switched to 0.05% atropine for continued treatment, whereas all treatment cessation subgroups followed a PRN re-treatment protocol to resume 0.05% atropine for children with myopic progressions of 0.5 diopter (D) or more over 1 year. Generalized estimating equations were used to compare the changes in spherical equivalent (SE) progression and axial length (AL) elongation among groups. (1) Changes in SE and AL in different groups over 5 years, (2) the proportion of children who needed re-treatment, and (3) changes in SE and AL in the continued treatment and PRN re-treatment groups from years 3 to 5. Two hundred seventy (82.8%) of 326 children (82.5%) from the third year completed 5 years of follow-up. Over 5 years, the cumulative mean SE progressions were –1.34 ± 1.40 D, –1.97 ± 1.03 D, and –2.34 ± 1.71 D for the continued treatment groups with initial 0.05%, 0.025%, and 0.01% atropine, respectively (P = 0.02). Similar trends were observed in AL elongation (P = 0.01). Among the PRN re-treatment group, 87.9% of children (94/107) needed re-treatment. The proportion of re-treatment across all studied concentrations was similar (P = 0.76). The SE progressions for continued treatment and PRN re-treatment groups from years 3 to 5 were –0.97 ± 0.82 D and –1.00 ± 0.74 D (P = 0.55) and the AL elongations were 0.51 ± 0.34 mm and 0.49 ± 0.32 mm (P = 0.84), respectively. Over 5 years, the continued 0.05% atropine treatment demonstrated good efficacy for myopia control. Most children needed to restart treatment after atropine cessation at year 3. Restarted treatment with 0.05% atropine achieved similar efficacy as continued treatment. Children should be considered for re-treatment if myopia progresses after treatment cessation. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

(1) To compare the efficacy of continued and stopping treatment for 0.05%, 0.025%, and 0.01% atropine during the third year. (2) To evaluate the efficacy of continued treatment over 3 years. (3) To investigate the rebound phenomenon and its determinants after cessation of treatment. A randomized, double-masked extended trial. A total of 350 of 438 children aged 4 to 12 years originally recruited into the Low-Concentration Atropine for Myopia Progression (LAMP) study. At the beginning of the third year, children in each group were randomized at a 1:1 ratio to continued treatment and washout subgroups. Cycloplegic spherical equivalent (SE) refraction and axial length (AL) were measured at 4-month intervals. Changes in SE and AL between groups. A total of 326 children completed 3 years of follow-up. During the third year, SE progression and AL elongation were faster in the washout subgroups than in the continued treatment groups across all concentrations: –0.68 ± 0.49 diopters (D) versus –0.28 ± 0.42 D (P < 0.001) and 0.33 ± 0.17 mm versus 0.17 ± 0.14 mm (P < 0.001) for the 0.05%; –0.57 ± 0.38 D versus –0.35 ± 0.37 D (P = 0.004) and 0.29 ± 0.14 mm versus 0.20 ± 0.15 mm (P = 0.001) for the 0.025%; –0.56 ± 0.40 D versus –0.38 ± 0.49 D (P = 0.04) and 0.29 ± 0.15 mm versus 0.24 ± 0.18 mm (P = 0.13) for the 0.01%. Over the 3-year period, SE progressions were –0.73 ± 1.04 D, –1.31 ± 0.92 D, and –1.60 ± 1.32 D (P = 0.001) for the 0.05%, 0.025%, and 0.01% groups in the continued treatment subgroups, respectively, and −1.15 ± 1.13 D, –1.47 ± 0.77 D, and –1.81 ± 1.10 D (P = 0.03), respectively, in the washout subgroup. The respective AL elongations were 0.50 ± 0.40 mm, 0.74 ± 0.41 mm, and 0.89 ± 0.53 mm (P < 0.001) for the continued treatment subgroups and 0.70 ± 0.47 mm, 0.82 ± 0.37 mm, and 0.98 ± 0.48 mm (P = 0.04) for the washout subgroup. The rebound SE progressions during washout were concentration dependent, but their differences were clinically small (P = 0.15). Older age and lower concentration were associated with smaller rebound effects in both SE progression (P < 0.001) and AL elongation (P < 0.001). During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. 0.05% atropine remained the optimal concentration over 3 years in Chinese children. The differences in rebound effects were clinically small across all 3 studied atropine concentrations. Stopping treatment at an older age and lower concentration are associated with a smaller rebound. [ABSTRACT FROM AUTHOR]

To investigate the effect of age at treatment and other factors on treatment response to atropine in the Low-Concentration Atropine for Myopia Progression (LAMP) Study. Secondary analysis from a randomized trial. Three hundred fifty children aged 4 to 12 years who originally were assigned to receive 0.05%, 0.025%, or 0.01% atropine or placebo once daily, and who completed 2 years of the LAMP Study, were included. In the second year, the placebo group was switched to the 0.05% atropine group. Potential predictive factors for change in spherical equivalent (SE) and axial length (AL) over 2 years were evaluated by generalized estimating equations in each treatment group. Evaluated factors included age at treatment, gender, baseline refraction, parental myopia, time outdoors, diopter hours of near work, and treatment compliance. Estimated mean values and 95% confidence intervals (CIs) of change in SE and AL over 2 years also were generated. Factors associated with SE change and AL change over 2 years were the primary outcome measures. Associated factors during the first year were secondary outcome measures. In 0.05%, 0.025%, and 0.01% atropine groups, younger age was the only factor associated with SE progression (coefficient of 0.14, 0.15, and 0.20, respectively) and AL elongation (coefficient of –0.10, –0.11, and –0.12, respectively) over 2 years; the younger the age, the poorer the response. At each year of age from 4 to 12 years across the treatment groups, higher-concentration atropine showed a better treatment response, following a concentration-dependent effect (P trend <0.05 for each age group). In addition, the mean SE progression in 6-year-old children receiving 0.05% atropine (–0.90 diopter [D]; 95% CI, –0.99 to –0.82) was similar to that of 8-year-old children receiving 0.025% atropine (–0.89 D; 95% CI, –0.94 to –0.83) and 10-year-old children receiving 0.01% atropine (–0.92 D; 95% CI, –0.99 to –0.85). All concentrations were well tolerated in all age groups. Younger age is associated with poor treatment response to low-concentration atropine at 0.05%, 0.025%, and 0.01%. Among concentrations studied, younger children required the highest 0.05% concentration to achieve similar reduction in myopic progression as older children receiving lower concentrations. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of 0.05%, 0.025%, and 0.01% atropine eye drops over 2 years to determine which is the optimal concentration for longer-term myopia control. Randomized, double-masked trial extended from the Low-Concentration Atropine for Myopia Progression (LAMP) Study. Three hundred eighty-three of 438 children (87%) aged 4 to 12 years with myopia of at least –1.0 diopter (D) originally randomized to receive atropine 0.05%, 0.025%, 0.01%, or placebo once daily in both eyes in the LAMP phase 1 study were continued in this extended trial (phase 2). Children in the placebo group (phase 1) were switched to receive 0.05% atropine from the beginning of the second-year follow-up, whereas those in the 0.05%, 0.025%, and 0.01% atropine groups continued with the same regimen. Cycloplegic refraction, axial length (AL), accommodation amplitude, photopic and mesopic pupil diameter, and best-corrected visual acuity were measured at 4-month intervals. Changes in spherical equivalent (SE) and AL and their differences between groups. Over the 2-year period, the mean SE progression was 0.55±0.86 D, 0.85±0.73 D, and 1.12±0.85 D in the 0.05%, 0.025%, and 0.01% atropine groups, respectively (P = 0.015, P < 0.001, and P = 0.02, respectively, for pairwise comparisons), with mean AL changes over 2 years of 0.39±0.35 mm, 0.50±0.33 mm, and 0.59±0.38 mm (P = 0.04, P < 0.001, and P = 0.10, respectively). Compared with the first year, the second-year efficacy of 0.05% and 0.025% atropine remained similar (P >0.1), but improved mildly in the 0.01% atropine group (P = 0.04). For the phase 1 placebo group, the myopia progression was reduced significantly after switching to 0.05% atropine (SE change, 0.18 D in second year vs. 0.82 D in first year P < 0.001]; AL elongated 0.15 mm in second year vs. 0.43 mm in first year P < 0.001]). Accommodation loss and change in pupil size in all concentrations remained similar to the first-year results and were well tolerated. Visual acuity and vision-related quality of life remained unaffected. Over 2 years, the efficacy of 0.05% atropine observed was double that observed with 0.01% atropine, and it remained the optimal concentration among the studied atropine concentrations in slowing myopia progression. [ABSTRACT FROM AUTHOR]