Two-Year Results of 0.01% Atropine Eye Drops and 0.1% Loading Dose for Myopia Progression Reduction in Danish Children: A Placebo-Controlled, Randomized Clinical Trial.

We investigated the two-year safety and efficacy of 0.1% loading dose and 0.01% low-dose atropine eye drops in Danish children for reduction in myopia progression in an investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months and then 0.01% for eighteen months (loading dose group, N = 33), 0.01% for two years (0.01% group, N = 32) or placebo for two years (placebo, N = 32). Axial length (AL) and spherical equivalent refraction (SER) were primary outcomes. Secondary outcomes included adverse events and reactions, choroidal thickness, and other ocular biometrical measures. Outcomes were measured from baseline and at six-month intervals. Individual eyes nested by participant ID were analyzed with linear-mixed model analysis. Data were analyzed with intention-to-treat. Mean AL was 0.08 mm less (95% confidence interval (CI): -0.01; 0.17, p-value = 0.08) in the 0.1% loading dose and 0.10 mm less (95% CI: 0.01; 0.19, p-value = 0.02) in the 0.01% group after two years of treatment compared to placebo. Mean SER progression was 0.12 D (95% CI: -0.10; 0.33) less in the loading dose and 0.26 D (95% CI: 0.04; 0.48) less in the 0.01% groups after two years of treatment compared to placebo (p-value = 0.30 and 0.02, respectively). In total, 17 adverse events were reported in the second-year follow-up, and all were rated as mild. Adjusting for iris color did not affect treatment effect estimates. Intra-ocular pressure increased over two years comparably between all groups but remained within normal limits. Two-year treatment with 0.01% low-dose atropine eye drops is a safe and moderately efficacious intervention in Danish children for reducing myopia progression.

Safety and efficacy of 0.01% and 0.1% low-dose atropine eye drop regimens for reduction of myopia progression in Danish children: a randomized clinical trial examining one-year effect and safety.

BACKGROUND: To investigate the efficacy and safety of 0.1% and 0.01% low-dose atropine eye drops in reducing myopia progression in Danish children. METHODS: Investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months followed by 0.01% for six months (loading dose group, Number (N) = 33), 0.01% for twelve months (0.01% group, N = 32) or vehicle for twelve months (placebo, N = 32). Primary outcomes were axial length and spherical equivalent refraction. Secondary outcomes included adverse events and reactions, choroidal thickness and ocular biometry. Outcomes were measured at baseline and three-month intervals. Data was analyzed with linear-mixed model analysis according to intention-to-treat. RESULTS: Mean axial elongation was 0.10 mm less (95% confidence interval (CI): 0.17; 0.02, adjusted-p = 0.06) in the 0.1% loading dose and 0.07 mm less (95% CI: 0.15; 0.00, adjusted-p = 0.16) in the 0.01% group at twelve months compared to placebo. Mean spherical equivalent refraction progression was 0.24 D (95% CI: 0.05; 0.42) less in the loading dose and 0.19 D (95% CI: 0.00; 0.38) less in the 0.01% groups at twelve months, compared to placebo (adjusted-p = 0.06 and 0.14, respectively). A total of 108 adverse events were reported during the initial six-month loading dose period, primarily in the loading dose group, and 14 were reported in the six months following dose switching, all deemed mild except two serious adverse events, unrelated to the intervention. CONCLUSIONS: Low-dose atropine eye drops are safe over twelve months in otherwise healthy children. There may be a modest but clinically relevant reduction in myopia progression in Danish children after twelve months treatment, but the effect was statistically non-significant after multiple comparisons adjustment. After dose-switching at six months the loading dose group approached the 0.01% group, potentially indicating an early "rebound-effect". TRIAL REGISTRATION: this study was registered in the European Clinical Trials Database (EudraCT, number: 2018-001286-16) 05/11/2018 and first posted at www. CLINICALTRIALS: gov (NCT03911271) 11/04/2019, prior to initiation.

Phosphorylation of Schizosaccharomyces pombe Dss1 mediates direct binding to the ubiquitin-ligase Dma1 in vitro.

Intrinsically disordered proteins (IDPs) are often multifunctional and frequently posttranslationally modified. Deleted in split hand/split foot 1 (Dss1-Sem1 in budding yeast) is a highly multifunctional IDP associated with a range of protein complexes. However, it remains unknown if the different functions relate to different modified states. In this work, we show that Schizosaccharomyces pombe Dss1 is a substrate for casein kinase 2 in vitro, and we identify three phosphorylated threonines in its linker region separating two known disordered ubiquitin-binding motifs. Phosphorylations of the threonines had no effect on ubiquitin-binding but caused a slight destabilization of the C-terminal α-helix and mediated a direct interaction with the forkhead-associated (FHA) domain of the RING-FHA E3-ubiquitin ligase defective in mitosis 1 (Dma1). The phosphorylation sites are not conserved and are absent in human Dss1. Sequence analyses revealed that the Txx(E/D) motif, which is important for phosphorylation and Dma1 binding, is not linked to certain branches of the evolutionary tree. Instead, we find that the motif appears randomly, supporting the mechanism of ex nihilo evolution of novel motifs. In support of this, other threonine-based motifs, although frequent, are nonconserved in the linker, pointing to additional functions connected to this region. We suggest that Dss1 acts as an adaptor protein that docks to Dma1 via the phosphorylated FHA-binding motifs, while the C-terminal α-helix is free to bind mitotic septins, thereby stabilizing the complex. The presence of Txx(D/E) motifs in the disordered regions of certain septin subunits may be of further relevance to the formation and stabilization of these complexes.

Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation.

Growth hormone (GH) acts via JAK2 and LYN to regulate growth, metabolism, and neural function. However, the relationship between these tyrosine kinases remains enigmatic. Through an interdisciplinary approach combining cell biology, structural biology, computation, and single-particle tracking on live cells, we find overlapping LYN and JAK2 Box1-Box2-binding regions in GH receptor (GHR). Our data implicate direct competition between JAK2 and LYN for GHR binding and imply divergent signaling profiles. We show that GHR exhibits distinct mobility states within the cell membrane and that activation of LYN by GH mediates GHR immobilization, thereby initiating its nanoclustering in the membrane. Importantly, we observe that LYN mediates cytokine receptor degradation, thereby controlling receptor turnover and activity, and this applies to related cytokine receptors. Our study offers insight into the molecular interactions of LYN with GHR and highlights important functions for LYN in regulating GHR nanoclustering, signaling, and degradation, traits broadly relevant to many cytokine receptors.

IMI-Onset and Progression of Myopia in Young Adults.

Myopia typically starts and progresses during childhood, but onset and progression can occur during adulthood. The goals of this review are to summarize published data on myopia onset and progression in young adults, aged 18 to 40 years, to characterize myopia in this age group, to assess what is currently known, and to highlight the gaps in the current understanding. Specifically, the peer-reviewed literature was reviewed to: characterize the timeline and age of stabilization of juvenile-onset myopia; estimate the frequency of adult-onset myopia; evaluate the rate of myopia progression in adults, regardless of age of onset, both during the college years and later; describe the rate of axial elongation in myopic adults; identify risk factors for adult onset and progression; report myopia progression and axial elongation in adults who have undergone refractive surgery; and discuss myopia management and research study design. Adult-onset myopia is common, representing a third or more of all myopia in western populations, but less in East Asia, where onset during childhood is high. Clinically meaningful myopia progression continues in early adulthood and may average 1.00 diopters (D) between 20 and 30 years. Higher levels of myopia are associated with greater absolute risk of myopia-related ocular disease and visual impairment, and thus myopia in this age group requires ongoing management. Modalities established for myopia control in children would be options for adults, but it is difficult to predict their efficacy. The feasibility of studies of myopia control in adults is limited by the long duration required.

Reproducibility of Mesopic and Photopic Pupil Sizes in Myopic Children Using a Dedicated Pupillometer with Human-Assisted or Automated Reading.

This study aimed to investigate the reproducibility of pupil size measurements over time and between reading methods when comparing human-assisted reading to automated reading. Pupillary data were analyzed on a subset of myopic children enrolled in a multicenter randomized clinical trial on myopia control with low-dose atropine. Pupil size measurements were obtained prior to randomization at two time points (screening and baseline visits) using a dedicated pupillometer under mesopic and photopic conditions. A customized algorithm was built to perform automated readings, allowing comparisons between human-assisted and automated readings. Reproducibility analyses followed the principles of Bland and Altman and included the calculation of the mean difference between measurements and limits of agreement (LOA). We included 43 children. Mean (standard deviation) age was 9.8 (1.7) years and 25 (58%) children were girls. Using human-assisted readings, reproducibility over time showed mesopic mean difference of 0.02 mm with LOA from -0.87 mm to 0.91 mm, whereas photopic mean difference was -0.01 mm with LOA from -0.25 mm to 0.23 mm. Reproducibility between human-assisted and automated readings was also higher under photopic conditions, with mean difference of 0.03 mm and LOA from -0.03 mm to 0.10 mm at screening and mean difference of 0.03 mm and LOA from -0.06 mm to 0.12 mm at baseline. Using a dedicated pupillometer, we found that examinations performed under photopic conditions demonstrated higher reproducibility over time and between reading methods. We speculate whether mesopic measurements are sufficiently reproducible to be monitored over time. Furthermore, photopic measurements may be of greater relevance when evaluating the side effects of atropine treatment, such as photophobia.

Myopia Control with Low-Dose Atropine in European Children: Six-Month Results from a Randomized, Double-Masked, Placebo-Controlled, Multicenter Study.

The effect and safety of low-dose atropine in myopia control have not been studied in randomized, placebo-controlled trials outside Asia. We investigated the efficacy and safety of 0.1% atropine loading dose and 0.01% atropine compared with a placebo in a European population. Investigator-initiated, randomized, double-masked, placebo-controlled, equal-allocation, multicenter study comparing 0.1% atropine loading dose (six months) followed by 0.01% atropine (18 months), 0.01% atropine (24 months), and placebo (24 months). Participants were monitored for a 12-months washout period. Outcome measures were axial length (AL), cycloplegic spherical equivalent (SE), photopic and mesopic pupil size, accommodation amplitude, visual acuity, intraocular pressure (IOP), and adverse reactions and events. We randomized 97 participants (mean [standard deviation] age, 9.4 [1.7] years; 55 girls (57%) and 42 boys (43%)). After six months, AL was 0.13 mm shorter (95% confidence interval [CI], -0.18 to -0.07 [adjusted p < 0.001]) with 0.1% atropine loading dose and 0.06 mm shorter (95% CI, -0.11 to -0.01 [adjusted p = 0.06]) with 0.01% atropine than in the placebo group. We observed similar dose-dependent changes in SE, pupil size, accommodation amplitude, and adverse reactions. No significant differences in visual acuity or IOP were found between groups, and no serious adverse reactions were reported. We found a dose-dependent effect of low-dose atropine in European children without adverse reactions requiring photochromatic or progressive spectacles. Our results are comparable to those observed in East Asia, indicating that results on myopia control with low-dose atropine are generalizable across populations with different racial backgrounds.

Low-Dose Atropine Induces Changes in Ocular Biometrics in Myopic Children: Exploring Temporal Changes by Linear Mixed Models and Contribution to Treatment Effect by Mediation Analyses.

This study aimed to investigate changes in non-cycloplegic ocular biometrics during the initial six months of treatment with a 0.1% atropine loading dose and 0.01% atropine compared with a placebo and analyze their contribution to the treatment effect on cycloplegic spherical equivalent (SE) progression. The study was based on a randomized, double-masked, placebo-controlled, multicenter trial evaluating a 0.1% atropine six-month loading dose and 0.01% atropine in reducing myopic progression in Danish children. The treatment phase was 24 months, and the washout phase was 12 months. Parameters measured included changes in axial length (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and choroidal thickness (ChT), while cycloplegic SE and lens power were calculated. Longitudinal changes and contributions to treatment effects were analyzed using constrained linear mixed models and mediation analyses, respectively. After six months, AL was 0.13 mm shorter (95% confidence interval [CI], -0.18 to -0.07 [adjusted p < 0.001]) and 0.06 mm shorter (95% CI, -0.11 to -0.01 [adjusted p = 0.060]) with a 0.1% atropine loading dose and 0.01% atropine, respectively, compared to the placebo group. Similar concentration-dependent changes were found with ACD, LT, VCD, ChT, and cycloplegic SE. Although the treatment effects trended toward concentration-dependent responses, only the treatment effect mediated by AL at three months differed significantly between 0.01% atropine and a 0.1% atropine loading dose (adjusted p = 0.023). Several ocular biometrics, including AL, ACD, and LT, changed dose-dependently during low-dose atropine treatment. Moreover, the treatment effect of atropine on SE progression was mediated by a subset of ocular biometrics, mainly AL, with trends toward concentration dependency and distributional shifts over time.

Deciphering the Alphabet of Disorder-Glu and Asp Act Differently on Local but Not Global Properties.

Compared to folded proteins, the sequences of intrinsically disordered proteins (IDPs) are enriched in polar and charged amino acids. Glutamate is one of the most enriched amino acids in IDPs, while the chemically similar amino acid aspartate is less enriched. So far, the underlying functional differences between glutamates and aspartates in IDPs remain poorly understood. In this study, we examine the differential effects of aspartate and glutamates in IDPs by comparing the function and conformational ensemble of glutamate and aspartate variants of the disordered protein Dss1, using a range of assays, including interaction studies, nuclear magnetic resonance spectroscopy, small-angle X-ray scattering and molecular dynamics simulation. First, we analyze the sequences of the rapidly growing database of experimentally verified IDPs (DisProt) and show that glutamate enrichment is not caused by a taxonomy bias in IDPs. From analyses of local and global structural properties as well as cell growth and protein-protein interactions using a model acidic IDP from yeast and three Glu/Asp variants, we find that while the Glu/Asp variants support similar function and global dimensions, the variants differ in their binding affinities and population of local transient structural elements. We speculate that these local structural differences may play roles in functional diversity, where glutamates can support increased helicity, important for folding and binding, while aspartates support extended structures and form helical caps, as well as playing more relevant roles in, e.g., transactivation domains and ion-binding.

Investigation of biases in convolutional neural networks for semantic segmentation using performance sensitivity analysis.

The application of deep neural networks for segmentation in medical imaging has gained substantial interest in recent years. In many cases, this variant of machine learning has been shown to outperform other conventional segmentation approaches. However, little is known about its general applicability. Especially the robustness against image modifications (e.g., intensity variations, contrast variations, spatial alignment) has hardly been investigated. Data augmentation is often used to compensate for sensitivity to such changes, although its effectiveness has not yet been studied. Therefore, the goal of this study was to systematically investigate the sensitivity to variations in input data with respect to segmentation of medical images using deep learning. This approach was tested with two publicly available segmentation frameworks (DeepMedic and TractSeg). In the case of DeepMedic, the performance was tested using ground truth data, while in the case of TractSeg, the STAPLE technique was employed. In both cases, sensitivity analysis revealed significant dependence of the segmentation performance on input variations. The effects of different data augmentation strategies were also shown, making this type of analysis a useful tool for selecting the right parameters for augmentation. The proposed analysis should be applied to any deep learning image segmentation approach, unless the assessment of sensitivity to input variations can be directly derived from the network.

Myopia prevalence in Denmark - a review of 140 years of myopia research.

PURPOSE: To evaluate potential changes in myopia prevalence in Denmark by revising more than 100 years of myopia research. METHODS: A systematic literature search was performed in the PubMed, Embase and Cochrane Library databases. Only studies reporting a myopia prevalence in Denmark were included. Myopia was defined using the definition in individual references. We did not restrict inclusion of studies to specific methods of measuring or evaluating refraction. As refraction changes throughout life, information from available studies was divided in relevant age groups. Chi-squared test was used when analysing the effect of sex and education on myopia prevalence except when the expected values were beneath 5, where Fisher's exact test was used. To further compare the effect of sex, we calculated the odds ratio of being myopic for females compared to males. RESULTS: We identified 29 Danish studies reporting on prevalence of myopia. The studies were performed between year 1882 and 2018. We found no strong evidence of an increase in myopia prevalence in Denmark. Increasing age was associated with an increased myopia prevalence up to the age of 60 years where after the prevalence decreased. Longer education and more intensive educational load were associated with myopia. Fourteen studies compared the prevalence of myopia between males and females and two of these studies found a significant higher prevalence in females. CONCLUSION: We evaluated nearly 140 years of myopia research in Denmark and did not find a convincing change in prevalence of myopia which is in contrast to the high prevalence of myopia reported in some parts of the world and the expected rise in myopia as predicted by WHO.

Neonatal vitamin D status and myopia in young adult men.

PURPOSE: The prevalence of myopia is increasing worldwide, and modifiable risk factors are thus important to identify. Season of birth has been associated with later myopia risk. Neonatal vitamin D status is highly dependent on season of birth due to maternal sun exposure late in gestation. We hypothesize that prenatal exposure to low levels of vitamin D can interfere with visual development in term-born infants and that this might contribute to adult visual dysfunction. The aim of this study was thus to compare neonatal vitamin D levels from stored dried blood spots taken shortly after birth among young term-born men with myopia (cases) and random controls with emmetropia. METHODS: In this case-control study, we analysed neonatal 25(OH)D3 levels of 457 myopic male cases and 1280 emmetropic male controls assessed for myopia at the mandatory Danish conscript examination. Data were analysed using logistic regression analysis and results presented as crude and adjusted for potential confounders namely maternal age, maternal ethnicity, maternal and paternal education and season of birth. RESULTS: We did not observe a seasonal variation in myopia risk, neither did we observe increased odds of myopia in relation to low neonatal 25(OH)D3 levels. CONCLUSION: The rapid increase in myopia does not seem related to neonatal vitamin D status.

The Longitudinal Danish High Myopia Study, Cohort 1948: at age 66 years visual ability is only occasionally affected by visual field defects.

PURPOSE: A descriptive study on visual fields, as part of a 50-year follow-up of high myopia in an unselected cohort-based Danish sample, now aged 66 years. METHODS: In a Copenhagen 1948 birth cohort (n = 9243), 39 individuals aged 14 years were identified with myopia of at least -6 D, and with regular clinical follow-ups since then. In 2002 (n = 34, age 54 years) and 2008 (n = 32, age 60), the individual ambulatory visual field was outlined by kinetic Goldmann large object perimetry (IV or V,4e). At age 66 years, 28 attended for the 2014-2015 follow-up, at which smaller Goldmann objects (II and I,4e) were added, further to identify relative defects. RESULTS: Repeated large object perimetry disclosed statistically significant general peripheral narrowing over the 12-13-year test period, though slight and without practical implications. Two new cases showing absolute defects were however added to the three already known. The addition of small Goldmann objects disclosed relative defects in another eight participants, in some to suggest a refraction-related pattern (fundus ectasia; uncorrected high myopia). However, comparing eyes with and without defects, statistical importance could not be attached to the degree of myopia, fundus ectasia or optic disc morphology (χ2 , n.s.). CONCLUSION: (i) Serial large object Goldmann isopters over the 'senior' decade up to age 66 demonstrated a slight general peripheral narrowing by age of visual fields in high myopia. (ii) Overall 42% of the participants had absolute or relative defects (in 5 and 8, respectively), however, without socio-visual consequences when binocular. (iii) Visual field loss by age still appears a minor issue in clinically unselected high myopia.

Analysis of intensity normalization for optimal segmentation performance of a fully convolutional neural network.

INTRODUCTION: Convolutional neural networks have begun to surpass classical statistical- and atlas based machine learning techniques in medical image segmentation in recent years, proving to be superior in performance and speed. However, a major challenge that the community faces are mismatch between variability within training and evaluation datasets and therefore a dependency on proper data pre-processing. Intensity normalization is a widely applied technique for reducing the variance of the data for which there are several methods available ranging from uniformity transformation to histogram equalization. The current study analyses the influence of intensity normalization on cerebellum segmentation performance of a convolutional neural network (CNN). METHOD: The study included three population samples with a total number of 218 datasets, all including a T1w MRI data set acquired at 3T and a ground truth segmentation delineating the cerebellum. A 12 layer deep 3D fully convolutional neural network was trained using 150 datasets from one of the population samples. Four different intensity normalization methods were separately applied to pre-process the data, and the CNN was correspondingly trained four times with respect to the different normalization techniques. A quantitative analysis of the segmentation performance, assessed via the Sørensen-Dice similarity coefficient (DSC) of all four CNNs, was performed to investigate the intensity sensitivity of the CNNs. Additionally, the optimal network performance was determined by identifying the best parameter set for intensity normalization. RESULTS: All four normalization methods led to excellent (mean DSC score=0.96) segmentation results when evaluated using known data; however, the segmentation performance differed depending on the applied intensity normalization method when testing with formerly unseen data, in which case the histogram equalization methods outperformed the unit distribution methods. A detailed, systematic analysis of intensity manipulations revealed, that the distribution of input intensities clearly affected the segmentation performance and that for each input dataset a linear intensity modification (shifting and scaling) existed leading to optimal segmentation results. This was further proven by an optimization analysis to find the optimal adjustment for an individual input evaluation sample within each normalization configuration. DISCUSSION: The findings suggest that proper preparation of the evaluation data is more crucial than the exact choice of normalization method to prepare the training data. The histogram equalization methods tested in this study were found to perform this task best, although leaving room for further improvements, as shown by the optimization analysis.

Choroidal thickness at age 66 years in the Danish high myopia study cohort 1948 compared with follow-up data on visual acuity over 40 years: a clinical update adding spectral domain optical coherence tomography.

BACKGROUND AND PURPOSE: A population-based Copenhagen birth year 1948 cohort with high myopia recorded since age 14 years (spherical equivalent less than or equivalent to -6 D) has been followed over 50 years. Despite complications, current follow-ups have outlined a better visual prognosis than usually drawn from selected clinical series in the literature. For the present status at age 66 years, focus was on visual ability and choroidal thickness. METHODS: Twenty-eight of the original 39 participants were available in 2014. Medical history was updated. Best-corrected visual acuity (BCVA) data were compared with subfoveal choroidal thickness (SFCT), now measured by enhanced depth optical coherence tomography. RESULTS: Due to at least better eye visual acuity (VA), all patients had maintained their everyday visual capacity. Only one participant was marginal regarding visual status for a driver's licence; low vision was not on record. Based on all eyes, choroidal thickness correlated negatively with axial length (AL), which also held for the fraction with high myopia (AL >26.5 mm). In high myopia, the mean choroidal subfoveal thickness was 114 ± 75 µm versus 182 ± 94 µm in lower myopia (p = 0.01). CONCLUSION: Despite the generally maintained individual visual capacity in the series, significant correlation could be demonstrated between SFCT and (i) axial elongation and (ii) recorded VA, with a negative and a positive sign, respectively. Overall, the visual prognosis was relatively benign, in particular when compared with the selected high myopia hospital series that predominate in the ophthalmic literature.

Choroidal thickness and myopia in relation to physical activity - the CHAMPS Eye Study.

PURPOSE: To describe the relationship between choroidal thickness (CT) and myopia in relation to physical activity (PA) in a population-based child cohort. METHODS: In a prospective study of 307 children from the CHAMPS Study Denmark, we used objective data from GT3X accelerometer worn at four periods between 2009 and 2015 to determine the amount and intensity of PA. Intensity was estimated as counts/minutes, and cut-off points were defined at four intensity levels. Eye examinations were performed in 2015 and included autorefraction in cycloplegia, axial length (AL) by biometric and fovea-centred enhanced depth imaging optical coherence tomography. By a semi-automated method, we measured the CT at 17 targets per eye representing anatomically different locations (subfoveal, 1 and 3 millimetre in each direction of fovea). RESULTS: Mean age at the eye examination was 15.4 ± 0.7 years. The mean AL was 23.5 ± 0.9 mm, and the mean subfoveal CT was 369 ± 87 µm. Choroidal thickness (CT) was 331 ± 68 µm for the overall macula, 355 ± 78 µm for the 1-mm zone and 304 ± 60 µm for the 3-mm zone. All CT measurements were thinner in myopic eyes (p < 0.0001) and in boys (p < 0.05). We found no association between total PA and the CT by either mixed model analysis (p = 0.074) or linear regression by any intensity levels (p = 0.22, p = 0.15 and p = 0.43). CONCLUSION: Among adolescents aged 14-17 years, there was no association between objective PA exposures and the CT, AL or refractive error.

Physical activity and myopia in Danish children-The CHAMPS Eye Study.

PURPOSE: To determine associations between physical activity (PA) and myopia in Danish school children and investigate the prevalence of myopia. METHODS: This is a prospective study with longitudinal data on PA in a Danish child cohort. Physical activity (PA) was measured objectively by repeated ActiGraph accelerometer measurement four times with different intervals (1-2.5 years) at the mean ages 9.7, 11.0, 12.9 and 15.4 years. Mean intensity of PA was estimated as counts/minutes, and time spent in sedentary, light, moderate and vigorous PA was summed using defined cut-off points. The ophthalmologic examination was conducted at the mean age of 15.4 ± 0.7 years and included cycloplegic autorefraction and biometry. RESULTS: A total of 307 children participated in the Childhood Health, Activity, and Motor Performance School (CHAMPS) Eye Study. The cycloplegic spherical equivalent (SE) was 0.30 ± 1.46 dioptres. The prevalence of myopia was 17.9% (SE ≤-0.5 dioptres). Mean axial length (AL) was 23.5 ± 0.9 mm. For all participants, the overall mean daily distribution of PA was 67.2% in sedentary, 25.6% in light, 4.4% in moderate and 2.9% in vigorous PA. Age- and sex-adjusted linear regression showed no association between PA and SE or AL. In a prospective slope analysis, there was no association between accumulated PA during the 7 years and AL or SE. CONCLUSION: The prevalence of myopia among Danish children was 17.9%. By logistic regression and slope analysis, we found no association between PA and myopia, in this first of its kind study based on objective and repeated PA data.