Correlation between small-scale methylation changes and gene expression during the development of myopia.

Visually induced changes in the expression of early growth response-1 (EGR1), FBJ osteosarcoma oncogene (FOS), and NGFI-A binding protein-2 (NAB2) appear to form a part of a retinal network fundamental to ocular growth regulation, and thus, the development of myopia (short-sightedness). However, it is unclear how environmental (visual) cues are translated into these molecular changes. One possibility is through epigenetic modifications such as DNA methylation, a known regulator of such processes. By sequencing bisulfite-converted DNA amplicons, this study examined whether changes in DNA methylation occur within specific regulatory and promoter regions of EGR1, FOS, and NAB2 during the periods of increased and decreased ocular growth in chicks. Visually induced changes in ocular growth rates were associated with single-point, but not large-scale, shifts in methylation levels within the investigated regions. Analysis of methylation pattern variability (entropy) demonstrated that the observed methylation changes are occurring within small subpopulations of retinal cells. This concurs with previous observations that EGR1 and FOS are differentially regulated at the peptide level within specific retinal cell types. Together, the findings of this study support a potential role for DNA methylation in the translation of external visual cues into molecular changes critical for ocular growth regulation and myopia development.

Pincus blob elasticity in an intrinsically disordered protein.

Understanding the dynamic structure of intrinsically disordered proteins (IDPs) is important to deciphering their biological functions. Here, we exploit precision entropic elasticity measurements to infer the conformational behavior of a model IDP construct formed from the disordered tail of the neurofilament low molecular weight protein. The IDP construct notably displays a low-force power-law elastic regime, consistent with the Pincus blob model, which allows direct extraction of the Flory exponent, [Formula: see text], from the force-extension relationship. We find [Formula: see text] increases with added denaturant, transitioning from a nearly ideal chain to a swollen chain in a manner quantitatively consistent with measurements of IDP dimensions from other experimental techniques. We suggest that measurements of entropic elasticity could be broadly useful in the study of IDP structure.

The first consultation for low mood in general practice: what do patients find helpful?

BACKGROUND: Recent evidence suggests that the first consultation with a general practitioner (GP) for symptoms of depression may be more than just a vehicle for assessment and management planning (as current guidelines imply). OBJECTIVES: To identify what patients find helpful, or otherwise, in their first consultation for low mood with a GP. METHODS: A cross-sectional questionnaire and interview study of patients with low mood who had recently consulted their GP, in the North of England. Patients were asked to complete a questionnaire regarding the consultation, and a Patient Health Questionnaire-9 (PHQ-9), within 2 weeks. They were also invited to take part in a face-face interview with a researcher. Both sources of data were subjected to qualitative thematic analysis. RESULTS: Thirty-seven questionnaires were returned; 5 interviews took place. The majority of participants felt better after consulting a GP for the first time for low mood. The factors most commonly cited as helpful were "being listened to" and "understanding or empathy from the GP." Others included "admitting the problem," "being reassured of normality," and "being provided with optimism or hope for change." The most commonly reported difficulty was the patients' struggle to express themselves. Patients often felt that GP follow-up was inadequate. CONCLUSIONS: These results suggest that the therapeutic benefit of the GP consultation is under-recognized in current guidelines. The results of our study will provide crucial information as to how such consultations can be tailored to improve patient satisfaction.

Although patients often tell their general practitioner (GP) that they feel better after a first consultation with symptoms of depression, the degree of patient satisfaction after such consultations seems to vary greatly. In this questionnaire and interview study, patients were asked to state which aspects of the consultation they had found helpful, or otherwise. The results showed that well-recognized factors of patient-centredness (where patients are involved in all decisions about their healthcare) such as "having time to talk" and "being listened to" were highly valued in the current setting. In addition, several aspects of the GP consultation that are more specific to depression were also highly rated, namely: "Admitting the problem," "being reassured of normality," and "being provided with optimism or hope for change." Overall, most patients felt better after the first consultation for low mood­a therapeutic effect that is not well recognized in current guidelines for depression. However, patients consistently reported that they felt GP follow-up after their first consultation for low mood was insufficient. These results should help us to optimize GP consultations for patients presenting for the first symptoms of depression.

Time outdoors positively associates with academic performance: a school-based study with objective monitoring of outdoor time.

BACKGROUND: To explore the relationship between outdoor time and academic performance among school-aged children. METHODS: This study was designed as a cross-sectional study. Data were derived from a school-based prospective children myopia intervention study (STORM). Outdoor time was recorded by self-developed algorithm-validated wristwatches in real-time and calculated as the cumulative average of 10 months. The academic performance was recorded and provided by the participating schools and further standardized. Other information was collected using an online standardized questionnaire. Mixed-effects model and B-Spline method were used to investigate the association between time spent on different types of daily activity, including outdoor activity and academic performance. RESULTS: A total of 3291 children with mean age 9.25 years were included in the final analysis. Overall, outdoor time was associated with academic performance in a non-linear manner; specifically, not exceeding 2.3 h per day, outdoor time was positively associated with academic performance; exceeding 2.3 h per day, this association became non-significant. Likewise, daily sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner, resulting in turning points of 11.3 and 1.4 h per day, respectively. Separate analysis showed that outdoor time and sleep duration but not out-of-school learning time were positively associated with academic performance in Chinese, mathematics and English. CONCLUSION: Outdoor time, sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner. Promotion of outdoor time may not negatively impact on academic performance. TRIAL REGISTRATION: Our study was registered in ClinicalTrials.gov (Identifier: NCT02980445).

Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children: A Multicenter Randomized Controlled Trial.

PURPOSE: To assess the efficacy and safety of repeated low-level red-light (RLRL) therapy in myopia control in children. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial. PARTICIPANTS: Two hundred sixty-four eligible children 8 to 13 years of age with myopia of cycloplegic spherical equivalent refraction (SER) of -1.00 to -5.00 diopters (D), astigmatism of 2.50 D or less, anisometropia of 1.50 D or less, and best-corrected visual acuity (BCVA) of 0.0 logarithm of the minimum angle of resolution or more were enrolled in July and August 2019. Follow-up was completed in September 2020. METHODS: Children were assigned randomly to the intervention group (RLRL treatment plus single-vision spectacle [SVS]) and the control group (SVS). The RLRL treatment was provided by a desktop light therapy device that emits red light of 650-nm wavelength at an illuminance level of approximately 1600 lux and a power of 0.29 mW for a 4-mm pupil (class I classification) and was administered at home under supervision of parents for 3 minutes per session, twice daily with a minimum interval of 4 hours, 5 days per week. MAIN OUTCOME MEASURES: The primary outcome and a key secondary outcome were changes in axial length and SER measured at baseline and the 1-, 3-, 6-, and 12-month follow-up visits. Participants who had at least 1 postrandomization follow-up visit were analyzed for treatment efficacy based on a longitudinal mixed model. RESULTS: Among 264 randomized participants, 246 children (93.2%) were included in the analysis (117 in the RLRL group and 129 in the SVS group). Adjusted 12-month axial elongation and SER progression were 0.13 mm (95% confidence interval [CI], 0.09-0.17mm) and -0.20 D (95% CI, -0.29 to -0.11D) for RLRL treatment and 0.38 mm (95% CI, 0.34-0.42 mm) and -0.79 D (95% CI, -0.88 to -0.69 D) for SVS treatment. The differences in axial elongation and SER progression were 0.26 mm (95% CI, 0.20-0.31 mm) and -0.59D (95% CI, -0.72 to -0.46 D) between the RLRL and SVS groups. No severe adverse events (sudden vision loss ≥2 lines or scotoma), functional visual loss indicated by BCVA, or structural damage seen on OCT scans were observed. CONCLUSIONS: Repeated low-level red-light therapy is a promising alternative treatment for myopia control in children with good user acceptability and no documented functional or structural damage.

Time Outdoors in Reducing Myopia: A School-Based Cluster Randomized Trial with Objective Monitoring of Outdoor Time and Light Intensity.

PURPOSE: To evaluate the efficacy of time outdoors per school day over 2 years on myopia onset and shift. DESIGN: A prospective, cluster-randomized, examiner-masked, 3-arm trial. PARTICIPANTS: A total of 6295 students aged 6 to 9 years from 24 primary schools in Shanghai, China, stratified and randomized by school in a 1:1:1 ratio to control (n = 2037), test I (n = 2329), or test II (n = 1929) group. METHODS: An additional 40 or 80 minutes of outdoor time was allocated to each school day for test I and II groups. Children in the control group continued their habitual outdoor time. Objective monitoring of outdoor and indoor time and light intensity each day was measured with a wrist-worn wearable during the second-year follow-up. MAIN OUTCOME MEASURES: The 2-year cumulative incidence of myopia (defined as cycloplegic spherical equivalent [SE] of ≤-0.5 diopters [D] in the right eye) among the students without myopia at baseline and changes in SE and axial length (AL) after 2 years. RESULTS: The unadjusted 2-year cumulative incidence of myopia was 24.9%, 20.6%, and 23.8% for control, test I, and II groups, respectively. The adjusted incidence decreased by 16% (incidence risk ratio [IRR], 0.84; 95% confidence interval [CI], 0.72-0.99; P = 0.035) in test I and 11% (IRR = 0.89; 95% CI, 0.79-0.99; P = 0.041) in test II when compared with the control group. The test groups showed less myopic shift and axial elongation compared with the control group (test I: -0.84 D and 0.55 mm, test II: -0.91 D and 0.57 mm, control: -1.04 D and 0.65 mm). There was no significant difference in the adjusted incidence of myopia and myopic shift between the 2 test groups. The test groups had similar outdoor time and light intensity (test I: 127 ± 30 minutes/day and 3557 ± 970 lux/minute; test II: 127 ± 26 minutes/day and 3662 ± 803 lux/minute) but significantly more outdoor time and higher light intensity compared with the control group (106 ± 27 minutes/day and 2984 ± 806 lux/minute). Daily outdoor time of 120 to 150 minutes at 5000 lux/minutes or cumulative outdoor light intensity of 600 000 to 750 000 lux significantly reduced the IRR by 15%～ 24%. CONCLUSIONS: Increasing outdoor time reduced the risk of myopia onset and myopic shifts, especially in nonmyopic children. The protective effect of outdoor time was related to the duration of exposure and light intensity. The dose-response effect between test I and test II was not observed probably because of insufficient outdoor time achieved in the test groups, which suggests that proper monitoring on the compliance on outdoor intervention is critical if one wants to see the protective effect.

Transcriptome-based insights into gene networks controlling myopia prevention.

Myopia (short-sightedness), usually caused by excessive elongation of the eye during development, has reached epidemic proportions worldwide. In animal systems including the chicken model, several treatments have been shown to inhibit ocular elongation and experimental myopia. Although diverse in their apparent mechanism of action, each one leads to a reduction in the rate of ocular growth. We hypothesize that a defined set of retinal molecular changes may underlie growth inhibition, irrespective of the treatment agent used. Accordingly, across five well-established but diverse methods of inhibiting myopia, significant overlap is seen in the retinal transcriptome profile (transcript levels and alternative splicing events) in chicks when analyzed by RNA-seq. Within the two major pathway networks enriched during growth inhibition, that of cell signaling and circadian entrainment, transcription factors form the largest functional grouping. Importantly, a large percentage of those genes forming the defined retinal response are downstream targets of the transcription factor EGR1 which itself shows a universal response to all five growth-inhibitory treatments. This supports EGR1's previously implicated role in ocular growth regulation. Finally, by contrasting our data with human linkage and GWAS studies on refractive error, we confirm the applicability of our study to the human condition. Together, these findings suggest that a universal set of transcriptome changes, which sit within a well-defined retinal network that cannot be bypassed, is fundamental to growth regulation, thus paving a way for designing novel targets for myopia therapies.

Sustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study.

BACKGROUND: To evaluate the long-term efficacy and safety of continued repeated low-level red-light (RLRL) therapy on myopia control over 2 years, and the potential rebound effect after treatment cessation. METHODS: The Chinese myopic children who originally completed the one-year randomised controlled trial were enrolled. Children continued RLRL-therapy were defined as RLRL-RLRL group, while those who stopped and switched to single-vision spectacle (SVS) in the second year were RLRL-SVS group. Likewise, those who continued to merely wear SVS or received additional RLRL-therapy were SVS-SVS and SVS-RLRL groups, respectively. RLRL-therapy was provided by an at-home desktop light device emitting red-light of 650 nm and was administered for 3 min at a time, twice a day and 5 days per week. Changes in axial length (AL) and cycloplegic spherical equivalence refraction (SER) were measured. RESULTS: Among the 199 children who were eligible, 138 (69.3%) children attended the examination and 114 (57.3%) were analysed (SVS-SVS: n = 41; SVS-RLRL: n = 10; RLRL-SVS: n = 52; RLRL-RLRL: n = 11). The baseline characteristics were balanced among four groups. In the second year, the mean changes in AL were 0.28 ± 0.14 mm, 0.05 ± 0.24 mm, 0.42 ± 0.20 mm and 0.12 ± 0.16 mm in SVS-SVS, SVS-RLRL, RLRL-SVS and RLRL-RLRL group, respectively (p < 0.001). The respective mean SER changes were -0.54 ± 0.39D, -0.09 ± 0.55D, -0.91 ± 0.48D, and -0.20 ± 0.56D (p < 0.001). Over the 2-year period, axial elongation and SER progression were smallest in RLRL-RLRL group (AL: 0.16 ± 0.37 mm; SER: -0.31 ± 0.79D), followed by SVS-RLRL (AL: 0.44 ± 0.37 mm; SER: -0.96 ± 0.70D), RLRL-SVS (AL: 0.50 ± 0.28 mm; SER: -1.07 ± 0.69D) and SVS-SVS group (AL: 0.64 ± 0.29 mm; SER: -1.24 ± 0.63D). No self-reported adverse events, functional or structural damages were noted. CONCLUSIONS: Continued RLRL therapy sustained promising efficacy and safety in slowing myopia progression over 2 years. A modest rebound effect was noted after treatment cessation.

Heisenberg Spin Chains via Chalcogen Bonding: Noncovalent S···O Contacts Enable Long-Range Magnetic Order.

The new radical ligand 5,8-dimethyl-1,4-dioxonaphtho[2,3-d][1,2,3]dithiazolyl (1) is reported. Two crystal polymorphs, 1α and 1ß, differing in their pancake-bonded dimerization motif and S···O contact network, are identified. The self-assembly of Mn(II) metal ions with 1 leads to the formation of [Mn(hfac)2]3(1)2 that exhibits a Mn(II)-radical-Mn(II)-radical-Mn(II) linear arrangement of three Mn(hfac)2 units bridged by two radical ligands (hfac = 1,1,1,5,5,5-hexafluoroacetylacetonato-). Characterization by single-crystal X-ray diffraction of this Mn(II) complex packing structure reveals close noncovalent S···O contacts between the [Mn(hfac)2]3(1)2 units in one dimension along the b-c direction. The magnetic properties of the coordination complex are characterized by dc and ac susceptibility measurements on a microcrystalline solid. The magnetic data down to 4.8 K indicate the presence of effective ferromagnetic interactions (J/kB = +0.16 K) between the molecular ST = 13/2 units along the supramolecular chain involving noncovalent S···O contacts. Below 2.9 K, a non-zero out-of-phase component appears in the ac susceptibility, indicating the presence of a three-dimensional magnetic phase transition.

A Peer-to-Peer Live-Streaming Intervention for Children During COVID-19 Homeschooling to Promote Physical Activity and Reduce Anxiety and Eye Strain: Cluster Randomized Controlled Trial.

BACKGROUND: The COVID-19 pandemic has led to worldwide school closures, with millions of children confined to online learning at home. As a result, children may be susceptible to anxiety and digital eye strain, highlighting a need for population interventions. OBJECTIVE: The objective of our study was to investigate whether a digital behavior change intervention aimed at promoting physical activity could reduce children's anxiety and digital eye strain while undergoing prolonged homeschooling during the COVID-19 pandemic. METHODS: In this cluster randomized controlled trial, homeschooled grade 7 students at 12 middle schools in southern China were recruited through local schools and randomly assigned by the school to receive (1:1 allocation): (1) health education information promoting exercise and ocular relaxation, and access to a digital behavior change intervention, with live streaming and peer sharing of promoted activities (intervention), or (2) health education information only (control). The primary outcome was change in self-reported anxiety score. Secondary outcomes included change in self-reported eye strain and sleep quality. RESULTS: On March 16, 2020, 1009 children were evaluated, and 954 (94.5%) eligible children of consenting families were included in the intention-to-treat analysis. Children in the intervention (n=485, 6 schools) and control (n=469, 6 schools) groups were aged 13.5 (SD 0.5) years, and 52.3% (n=499) were male. The assigned interventions were completed by 896 children (intervention: n=467, 96.3%; control: n=429, 91.5%). The 2-week change in square-root-transformed self-reported anxiety scores was greater in the intervention (-0.23, 95% CI -0.27 to -0.20) vs control group (0.12, 95% CI 0.09-0.16; unadjusted difference -0.36, 95% CI -0.63 to -0.08; P=.02). There was a significant reduction in square-root-transformed eye strain in the intervention group (-0.08, 95% CI -0.10 to 0.06) compared to controls (0.07, 95% CI 0.05-0.09; difference -0.15, 95% CI -0.26 to -0.03; P=.02). Change in sleep quality was similar between the two groups. CONCLUSIONS: This digital behavior change intervention reduced children's anxiety and eye strain during COVID-19-associated online schooling. TRIAL REGISTRATION: ClinicalTrials.gov NCT04309097; http://clinicaltrials.gov/ct2/show/NCT04309097.

Increased Time Outdoors Is Followed by Reversal of the Long-Term Trend to Reduced Visual Acuity in Taiwan Primary School Students.

PURPOSE: To investigate the change in the prevalence of reduced visual acuity (VA) in Taiwanese school children after a policy intervention promoting increased time outdoors. DESIGN: Prospective cohort study based on the Taiwan School Student Visual Acuity Screen (TSVAS) by the Ministry of Education in Taiwan. PARTICIPANTS: All school children from grades 1 through 6 were enrolled in the TSVAS from 2001 through 2015. METHODS: The TSVAS requires each school in Taiwan to perform measurements of uncorrected VA (UCVA) on all students in grades 1 through 6 every half year using a Tumbling E chart. Reduced VA was defined as UCVA of 20/25 or less. Data from 1.2 to 1.9 million primary school children each year were collected from 2001 through 2015. A policy program named Tian-Tian 120 encouraged schools to take students outdoors for 120 minutes every day for myopia prevention. It was instituted in September 2010. To investigate the impact of the intervention, a segmented regression analysis of interrupted time series was performed. MAIN OUTCOME MEASURES: Prevalence of reduced VA. RESULTS: From 2001 to 2011, the prevalence of reduced VA of school children from grades 1 through 6 increased from 34.8% (95% confidence interval [CI], 34.7%-34.9%) to 50.0% (95% CI, 49.9%-50.1%). After the implementation of the Tian-Tian 120 outdoor program, the prevalence decreased continuously from 49.4% (95% CI, 49.3%-49.5%) in 2012 to 46.1% (95% CI, 46.0%-46.2%) in 2015, reversing the previous long-term trend. For the segmented regression analysis controlling for gender and grade, a significant constant upward trend before the intervention in the mean annual change of prevalence was found (+1.58%; standard error [SE], 0.08; P < 0.001). After the intervention, the trend changed significantly, with a constant decrease by -2.34% annually (SE, 0.23; P < 0.001). CONCLUSIONS: Policy intervention to promote increased time outdoors in schools was followed by a reversal of the long-term trend toward increased low VA in school children in Taiwan. Because randomized trials have demonstrated outdoor exposure slowing myopia onset, interventions to promote increased time outdoors may be useful in other areas affected by an epidemic of myopia.

Glassy Dynamics and Memory Effects in an Intrinsically Disordered Protein Construct.

Glassy, nonexponential relaxations in globular proteins are typically attributed to conformational behaviors that are missing from intrinsically disordered proteins. Yet, we show that single molecules of a disordered-protein construct display two signatures of glassy dynamics, logarithmic relaxations and a Kovacs memory effect, in response to changes in applied tension. We attribute this to the presence of multiple independent local structures in the chain, which we corroborate with a model that correctly predicts the force dependence of the relaxation. The mechanism established here likely applies to other disordered proteins.

Prediction of myopia development among Chinese school-aged children using refraction data from electronic medical records: A retrospective, multicentre machine learning study.

BACKGROUND: Electronic medical records provide large-scale real-world clinical data for use in developing clinical decision systems. However, sophisticated methodology and analytical skills are required to handle the large-scale datasets necessary for the optimisation of prediction accuracy. Myopia is a common cause of vision loss. Current approaches to control myopia progression are effective but have significant side effects. Therefore, identifying those at greatest risk who should undergo targeted therapy is of great clinical importance. The objective of this study was to apply big data and machine learning technology to develop an algorithm that can predict the onset of high myopia, at specific future time points, among Chinese school-aged children. METHODS AND FINDINGS: Real-world clinical refraction data were derived from electronic medical record systems in 8 ophthalmic centres from January 1, 2005, to December 30, 2015. The variables of age, spherical equivalent (SE), and annual progression rate were used to develop an algorithm to predict SE and onset of high myopia (SE ≤ -6.0 dioptres) up to 10 years in the future. Random forest machine learning was used for algorithm training and validation. Electronic medical records from the Zhongshan Ophthalmic Centre (a major tertiary ophthalmic centre in China) were used as the training set. Ten-fold cross-validation and out-of-bag (OOB) methods were applied for internal validation. The remaining 7 independent datasets were used for external validation. Two population-based datasets, which had no participant overlap with the ophthalmic-centre-based datasets, were used for multi-resource validation testing. The main outcomes and measures were the area under the curve (AUC) values for predicting the onset of high myopia over 10 years and the presence of high myopia at 18 years of age. In total, 687,063 multiple visit records (≥3 records) of 129,242 individuals in the ophthalmic-centre-based electronic medical record databases and 17,113 follow-up records of 3,215 participants in population-based cohorts were included in the analysis. Our algorithm accurately predicted the presence of high myopia in internal validation (the AUC ranged from 0.903 to 0.986 for 3 years, 0.875 to 0.901 for 5 years, and 0.852 to 0.888 for 8 years), external validation (the AUC ranged from 0.874 to 0.976 for 3 years, 0.847 to 0.921 for 5 years, and 0.802 to 0.886 for 8 years), and multi-resource testing (the AUC ranged from 0.752 to 0.869 for 4 years). With respect to the prediction of high myopia development by 18 years of age, as a surrogate of high myopia in adulthood, the algorithm provided clinically acceptable accuracy over 3 years (the AUC ranged from 0.940 to 0.985), 5 years (the AUC ranged from 0.856 to 0.901), and even 8 years (the AUC ranged from 0.801 to 0.837). Meanwhile, our algorithm achieved clinically acceptable prediction of the actual refraction values at future time points, which is supported by the regressive performance and calibration curves. Although the algorithm achieved balanced and robust performance, concerns about the compromised quality of real-world clinical data and over-fitting issues should be cautiously considered. CONCLUSIONS: To our knowledge, this study, for the first time, used large-scale data collected from electronic health records to demonstrate the contribution of big data and machine learning approaches to improved prediction of myopia prognosis in Chinese school-aged children. This work provides evidence for transforming clinical practice, health policy-making, and precise individualised interventions regarding the practical control of school-aged myopia.

Surface-induced effects in fluctuation-based measurements of single-polymer elasticity: A direct probe of the radius of gyration.

Single-molecule measurements of polymer elasticity are powerful, direct probes of both biomolecular structure and principles of polymer physics. Recent work has revealed low-force regimes in which biopolymer elasticity is understood through blob-based scaling models. However, the small tensions required to observe these regimes have the potential to create measurement biases, particularly due to the increased interactions of the polymer chain with tethering surfaces. Here, we examine one experimentally observed bias, in which fluctuation-based estimates of elasticity report an unexpectedly low chain compliance. We show that the effect is in good agreement with predictions based on quantifying the exclusion effect of the surface through an image-method calculation of available polymer configurations. The analysis indicates that the effect occurs at an external tension inversely proportional to the polymer's zero-tension radius of gyration. We exploit this to demonstrate a self-consistent scheme for estimating the radius of gyration of the tethered polymer. This is shown in measurements of both hyaluronic acid and poly(ethylene glycol) chains.

Significant Axial Elongation with Minimal Change in Refraction in 3- to 6-Year-Old Chinese Preschoolers: The Shenzhen Kindergarten Eye Study.

PURPOSE: To document the distribution of ocular biometry and to evaluate its associations with refraction in a group of Chinese preschoolers. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of 1133 preschoolers 3 to 6 years of age from 8 representative kindergartens. METHODS: Biometric measurements including axial length (AL), anterior chamber depth (ACD), and corneal radius of curvature (CR) were obtained from partial-coherence laser interferometry (IOL Master; Carl Zeiss Meditec, Oberkochen, Germany) before cycloplegia. Lens power (LP) and AL-to-CR ratio were calculated. Cycloplegic refraction (3 drops of 1% cyclopentolate) was measured using an autorefractor (KR8800; Topcon Corp., Tokyo, Japan), and spherical equivalent refraction (SER) was calculated. Biometric and refractive parameters were assessed as a function of age and gender. Multiple regression analysis was performed to explore the associations between refraction and ocular biometry. MAIN OUTCOME MEASURES: Ocular biometric distributions and their relationships to refraction. RESULTS: Among the 1127 children (99.5%) with successful cycloplegic refraction, mean SER was 1.37±0.63 diopters (D). Prevalence of myopia increased from 0% at 3 years of age to 3.7% (95% confidence interval, 1.0%-6.5%) at 6 years of age. Biometric parameters followed Gaussian distributions with means of 22.39±0.68 mm for AL, 7.79±0.25 mm for CR, and 24.61±1.42 D for calculated LP; and non-Gaussian distributions with means of 3.34±0.24 mm for ACD and 2.88±0.06 for AL-to-CR ratio. Axial length, ACD, and AL-to-CR ratio increased from 3 to 6 years of age, CR remained stable, whereas LP declined. Overall, SER declined slightly. For the SER variance, AL explained 18.6% and AL-to-CR ratio explained 39.8%, whereas AL, CR, and LP accounted for 80.0% after adjusting for age and gender. CONCLUSIONS: Young Chinese children are predominantly mildly hyperopic, with a low prevalence of myopia by the age of 6 years. An increase of 1 mm in AL was associated with only 0.45 D of myopic change. Decreases in LP reduce the myopic shifts that normally would be associated with increases in AL, and thus play a key role in refractive development in this age group.

Three-Dimensional Eye Shape, Myopic Maculopathy, and Visual Acuity: The Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.

PURPOSE: To investigate the relationship among eye shape, myopic maculopathy, and visual acuity in highly myopic eyes using 3-dimensional (3D) magnetic resonance imaging (MRI). DESIGN: Observational case series. PARTICIPANTS: The study included 190 eyes of 95 participants with bilateral high myopia from the Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study, with spherical power ≤-6.00 diopters (D) in both eyes. METHODS: The participants underwent best-corrected visual acuity (BCVA), fundus photography, cycloplegic refraction, and ocular biometry. Posterior staphyloma was identified with 3D MRI, and ocular shapes were categorized into spheroidal, ellipsoidal, conical, nasally distorted, temporally distorted, and barrel shapes according to the inferior view from T2-weighted 3D MRI (Achieva 3.0T; Philips Medical Systems, Best, the Netherlands). Myopic maculopathy was graded as C0 to C4 according to the International Photographic Classification and Grading System using fundus photography. The statistical significance of the differences in distribution of myopic maculopathy and BCVA in eyes with different ocular shapes was determined using Pearson's chi-square tests. MAIN OUTCOME MEASURES: Distributions of myopic maculopathy and BCVA in relation to different eye shapes. RESULTS: The mean spherical equivalent and axial length were -11.74±4.10 D and 28.18±1.73 mm in the right eyes, respectively. The same ocular shapes were observed in both eyes in 69 participants (72.6%). The predominant shape was spheroidal (53.7%), followed by nasally distorted and conical types (both 14.7%). C2 and above myopic maculopathy was observed in all barrel-shaped eyes, in 75% temporally distorted eyes, and in 71.4% nasally distorted and conical eyes. In eyes with posterior staphyloma (n = 22), 18 (81.8%) had C2 and above myopic maculopathy compared with 40 eyes (54.8%) without posterior staphyloma (n = 73). Eyes with temporal and nasal distortion, and eyes with staphyloma were more likely to have BCVA <20/40. CONCLUSIONS: Not all highly myopic eyes are deformed. Spheroid was the predominant ocular shape in this series of young patients with high myopia bilaterally. Barrel-shaped and temporally distorted eyes present significant myopic maculopathy, whereas eyes with posterior staphyloma display more severe chorioretinal atrophy. Eyes of more deformed shapes tend to have more severe myopic maculopathy and worse BCVA.

Green spaces and spectacles use in schoolchildren in Barcelona.

Myopia is one of the major causes of low visual acuity during childhood, and hence of the need for spectacles. It is generally more prevalent in urban areas where children are often less exposed to green spaces than in rural areas. This study evaluated the association between exposure to green space and use of spectacles (as a surrogate measure for myopia) in a cohort of 2727 schoolchildren (7-10 years old) recruited from 39 primary schools in Barcelona (2012-2015). We assessed exposure to green spaces by characterizing outdoor surrounding greenness at home and school and during commuting using satellite data on greenness (Normalized Difference Vegetation Index). We also obtained data on the annual average time children spent playing in green spaces through questionnaires. Cross-sectional analyses were conducted based on prevalent cases of spectacles use at baseline data collection campaign and longitudinal analyses based on incident cases of spectacles use during the three-year period between the baseline and last data collection campaigns. An interquartile range (IQR) increase in exposure to green space at home (500m buffer) and school and during commuting was associated with respectively 14% (95% CI: 2%, 26%), 27% (95% CI: 6%, 44%), and 20% (95% CI: 5%, 33%) decrease in spectacles use in cross-sectional analyses. In longitudinal analyses, we observed a reduction of 23% (95% CI: 4%, 39%) and 34% (95% CI: 2%, 55%) associated with an IQR increase in greenness at home and school, respectively. Moreover, an IQR increase in time playing in green spaces was associated with a 28% (95% CI: 7%, 45%) reduction in the risk of spectacles use in the longitudinal analysis. Our observed reduced risk of spectacles use associated with higher contact with green space calls for more refined studies of the association between green spaces and refractive errors of visions.

EPIDEMIC OF PATHOLOGIC MYOPIA: What Can Laboratory Studies and Epidemiology Tell Us?

PURPOSE: To systematically review epidemiologic and laboratory studies on the etiology of high myopia and its links to pathologic myopia. METHODS: Regular Medline searches have been performed for the past 20 years, using "myopia" as the basic search term. The abstracts of all articles have been scrutinized for relevance, and where necessary, translations of articles in languages other than English were obtained. RESULTS: Systematic review shows that there is an epidemic of myopia and high myopia in young adults in East and Southeast Asia, with similar but smaller trends in other parts of the world. This suggests an impending epidemic of pathologic myopia. High myopia in young adults in East and Southeast Asia is now predominantly associated with environmental factors, rather than genetic background. Recent clinical trials show that the onset of myopia can be reduced by increasing the time children spend outdoors, and methods to slow the progression of myopia are now available. CONCLUSION: High myopia is now largely associated with environmental factors that have caused the epidemic of myopia in East and Southeast Asia. An important clinical question is whether the pathologic consequences of acquired high myopia are similar to those associated with classic genetic high myopia. Increased time outdoors can be used to slow the onset of myopia, whereas methods for slowing progression are now available clinically. These approaches should enable the current epidemics of myopia and high myopia to be turned around, preventing an explosion of pathologic myopia.