The causes and consequences of childhood myopia

Myopia is the eye disorder with the most rapid increase in prevalence worldwide. It develops in childhood with a peak incidence between 13-15 years. Especially high myopia, a refractive error of -6 diopters or more, increases the risk of permanent visual impairment during adulthood due to structural abnormalities of the retina and optic nerve. The causes of myopia are complex. Lifestyle factors in childhood, such as time spent outdoors and close work are risk factors. Moreover, genetic studies have revealed more than many factors associated with myopia. Pharmacological and optical interventions to inhibit myopia progression are becoming increasingly common. The ultimate goal of this thesis was to gain insight into the causes and consequences of childhood myopia. For this purpose we investigated the environmental and genetic factors of myopia, eye growth in children and ocular biometry development in subjects of the Generation R and ALSPAC study. We studied the consequences of high myopia on visual impairment in adults and found a strong association between axial length and visual impairment

Myopia progression from wearing first glasses to adult age: The DREAM Study

Purpose: Data on myopia progression during its entire course are scarce. The aim of this study is to investigate myopia progression in Europeans as a function of age and degree of myopia from first prescription to final refractive error. Methods: The Drentse Refractive Error and Myopia Study assessed data from a branch of opticians in the Netherlands from 1985 onwards in a retrospective study. First pair of glasses prescribed was defined as a spherical equivalent of refraction (SER) ≤-0.5 D to ≥-3.0 D. Subjects with prescriptions at an interval of at least 1 year were included in the analysis. Results: A total of 2555 persons (57.3% female) met the inclusion criteria. Those with first prescription before the age of 10 years showed the strongest progression (-0.50 D; IQR: -0.75 to -0.19) and a significantly (p<0.001) more negative median final SER (-4.48 D; IQR: -5.37 to -3.42). All children who developed SER ≤-3 D at 10 years were highly myopic (SER ≤-6D) as adults, children who had SER between -1.5 D and -3 D at 10 years had 46.0% risk of high myopia, and children with SER between -0.5 D and -1.5 D had 32.6% risk of high myopia. Myopia progression diminished with age; all refractive categories stabilised after age 15 years except for SER ≤-5 D who progressed up to -0.25 D annually until age 21 years. Conclusion: Our trajectories of the natural course of myopia progression may serve as a guide for myopia management in European children. SER at 10 years is an important prognostic indicator and will help determine treatment intensity

The impact of computer use on myopia development in childhood

Environmental factors are important in the development of myopia. There is still limited evidence as to whether computer use is a risk factor. The aim of this study is to investigate the association between computer use and myopia in the context of other near work activities. Within the birth cohort study Generation R, we studied 5074 children born in Rotterdam between 2002 and 2006. Refractive error and axial length was measured at ages 6 and 9. Information on computer use and outdoor exposure was obtained at age 3, 6 and 9 years using a questionnaire, and reading time and reading distance were assessed at age 9 years. Myopia prevalence (spherical equivalent ≤–0.5 dioptre) was 11.5% at 9 years. Mean computer use was associated with myopia at age 9 (OR = 1.005, 95% CI = 1.001–1.009), as was reading time and reading distance (OR = 1.031; 95% CI = 1.007–1.055 (5–10 h/wk); OR = 1.113; 95% CI = 1.073–1.155 (>10 h/wk) and OR = 1.072; 95% CI = 1.048–1.097 respectively). The combined effect of near work (computer use, reading time and reading distance) showed an increased odds ratio for myopia at age 9 (OR = 1.072; 95% CI = 1.047–1.098), while outdoor exposure showed a decreased odds ratio (OR = 0.996; 95% CI = 0.994–0.999) and the interaction term was significant (P = 0.036). From our results, we can conclude that within our sample of children, increased computer use is associated with myopia development. The effect of combined near work was decreased by outdoor exposure. The risks of digital devices on myopia and the protection by outdoor exposure should become widely known. Public campaigns are warranted

Growth in foetal life, infancy, and early childhood and the association with ocular biometry

Purpose: Ocular biometry varies within groups of emmetropic, hyperopic or myopic children. The aim of this study was to quantify the effect of foetal and infant growth on ocular biometry in early childhood, to determine the most important period for this association, and to examine genetic overlap with height and birth weight. Methods: 5931 children (50.1% girls) from a population-based prospective birth cohort study underwent intra-uterine and infant growth measurements at second and third trimester, and from birth to 72 months. An ophthalmic examination including axial length (mm) and corneal radius of curvature (mm) was performed at 6 years of age. The associations between prenatal and postnatal growth variables and axial length and corneal radius of curvature were assessed with conditional linear regression analyses. Weighted genetic risk scores for birth weight and height were calculated and causality was tested with Mendelian randomisation. Results: Weight and length from mid-pregnancy to 2 years of age were most important prognostic factors for axial length and corneal radius of curvature at age 4.9–9 years (mean 6.2 years S.D. 0.5). For height (Standard deviation score), the association with axial length and corneal radius of curvature was highest for the measurement at 12 months (β 0.171 p < 0.001 and 0.070 p < 0.001). The genetic height and birth weight risk scores were both significantly associated with ocular biometry. Conclusions: Larger neonates had longer axial length and greater corneal radius of curvature. Growth during pregnancy and 2 years postnatally is the most important period underlying this association and may be partly genetically determined by genes associated with height

Low serum vitamin D is associated with axial length and risk of myopia in young children

The aim of the study was to investigate the relationship between serum 25(OH)D levels and axial length (AL) and myopia in 6-year-old children. A total of 2666 children aged 6 years participating in the birth-cohort study Generation R underwent a stepwise eye examination. First, presenting visual acuity (VA) and AL were performed. Second, automated cycloplegic refraction was measured if LogMAR VA > 0.1. Serum 25-hydroxyvitamin D [25(OH)D] was determined from blood using liquid chromatography/tandem mass spectrometry. Vitamin D related SNPs were determined with a SNP array; outdoor exposure was assessed by questionnaire. The relationships between 25(OH)D and AL or myopia were investigated using linear and logistic regression analysis. Average 25(OH)D concentration was 68.8 nmol/L (SD ± 27.5; range 4–211); average AL 22.35 mm (SD ± 0.7; range 19.2–25.3); and prevalence of myopia 2.3 % (n = 62). After adjustment for covariates, 25(OH)D concentration (per 25 nmol/L) was inversely associated with AL (β −0.043; P < 0.01), and after additional adjusting for time spent outdoors (β −0.038; P < 0.01). Associations were not different between European and non-European children (β −0.037 and β −0.039 respectively). Risk of myopia (per 25 nmol/L) was OR 0.65 (95 % CI 0.46–0.92). None of the 25(OH)D related SNPs showed an association with AL or myopia. Lower 25(OH)D concentration in serum was associated with longer AL and a higher risk of myopia in these young children. This effect appeared independent of outdoor exposure and may suggest a more direct role for 25(OH)D in myopia pathogenesis

Axial length growth and the risk of developing myopia in European children

Purpose: To generate percentile curves of axial length (AL) for European children, which can be used to estimate the risk of myopia in adulthood. Methods: A total of 12 386 participants from the population-based studies Generation R (Dutch children measured at both 6 and 9 years of age; N = 6934), the Avon Longitudinal Study of Parents and Children (ALSPAC) (British children 15 years of age; N = 2495) and the Rotterdam Study III (RS-III) (Dutch adults 57 years of age; N = 2957) contributed to this study. Axial length (AL) and corneal curvature data were available for all participants; objective cycloplegic refractive error was available only for the Dutch participants. We calculated a percentile score for each Dutch child at 6 and 9 years of age. Results: Mean (SD) AL was 22.36 (0.75) mm at 6 years, 23.10 (0.84) mm at 9 years, 23.41 (0.86) mm at 15 years and 23.67 (1.26) at adulthood. Axial length (AL) differences after the age of 15 occurred only in the upper 50%, with the highest difference within the 95th percentile and above. A total of 354 children showed accelerated axial growth and increased by more than 10 percentiles from age 6 to 9 years; 162 of these children (45.8%) were myopic at 9 years of age, compared to 4.8% (85/1781) for the children whose AL did not increase by more than 10 percentiles. Conclusion: This study provides normative values for AL that can be used to monitor eye growth in European children. These results can help clinicians detect excessive eye growth at an early age, thereby facilitating decision-making with respect to interventions for preventing and/or controlling myopia

Subfoveal choroidal thickness at age 9 years in relation to clinical and perinatal characteristics in the population-based Generation R Study

Purpose: To assess the association between clinical and perinatal characteristics and subfoveal choroidal thickness in 9-year-old children. Methods: The study included data from the population-based Generation R cohort, whose participants underwent cycloplegic refractometry, ocular biometry, height, weight and subfoveal choroidal thickness measurements using a swept-source optical coherence tomography (SS-OCT) instrument. Birth parameters were obtained using medical records. Statistical analyses were performed using multivariate regression models adjusted for age, ethnicity and sex. Results: A total of 1018 children (52.5% girls, 47.5% boys) with a mean age of 9.9 ± 0.3 years and a mean cycloplegic spherical equivalent refraction of 0.80 ± 1.1 D in boys and 0.81 ± 1.4 in girls were eligible for analysis. The subfoveal choroid was 17 μm thicker in girls (298 ± 60.6 μm) than in boys (281 ± 55.0 μm; p < 0.001), a difference of 9.1 μm persisting after adjustment for age, ethnicity and axial length (p = 0.017). Subfoveal choroidal thickness decreased with increasing ocular axial length (−16.2 μm/mm, 95% CI −21.2 to −12.4, p < 0.001) and with increasing myopic refraction (−10.0 μm/D, 95% CI 6.8–13.1; p < 0.001, adjusted for age, ethnicity, axial length and sex) while it increase

Genetically low vitamin D concentrations and myopic refractive error: A Mendelian randomization study

Background: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia. Methods: We performed MR using results from a meta-analysis of refractive error (RE) genome-wide association study (GWAS) that included 37 382 and 8 376 adult participants of European and Asian ancestry, respectively, published by the Consortium for Refractive Error And Myopia (CREAM). We used single nucleotide polymorphisms (SNPs) i

The Complications of Myopia: A Review and Meta-Analysis

PURPOSE. To determine the risk between degree of myopia and myopic macular degeneration (MMD), retinal detachment (RD), cataract, open angle glaucoma (OAG), and blindness. METHODS. A systematic review and meta-analyses of studies published before June 2019 on myopia complications. Odds ratios (OR) per complication and spherical equivalent (SER) degree (low myopia SER –3.00 diopter [D]; moderate myopia SER ≤ –3.00 to > –6.00 D; high myopia SER ≤ –6.00 D) were calculated using fixed and random effects models. RESULTS. Low, moderate, and high myopia were all associated with increased risks of MMD (OR, 13.57, 95% confidence interval [CI], 6.18–29.79; OR, 72.74, 95% CI, 33.18–159.48; OR, 845.08, 95% CI, 230.05–3104.34, respectively); RD (OR, 3.15, 95% CI, 1.92–5.17; OR, 8.74, 95% CI, 7.28–10.50; OR, 12.62, 95% CI, 6.65–23.94, respectively); posterior subcapsular cataract (OR, 1.56, 95% CI, 1.32–1.84; OR, 2.55, 95% CI, 1.98–3.28; OR, 4.55, 95% CI, 2.66–7.75, respectively); nuclear cataract (OR, 1.79, 95% CI, 1.08–2.97; OR, 2.39, 95% CI, 1.03–5.55; OR, 2.87, 95% CI, 1.43–5.73, respecti

Phenotypic consequences of the GJD2 risk genotype in myopia development

PURPOSE. To study the relatively high effect of the refractive error gene GJD2 in human myopia, and to assess its relationship with refractive error, ocular biometry and lifestyle in various age groups. METHODS. The population-based Rotterdam Study (RS), high myopia case-control study MYopia STudy, and the birth-cohort study Generation R were included in this study. Spherical equivalent (SER), axial length (AL), axial length/corneal radius (AL/CR), vitreous depth (VD), and anterior chamber depth (ACD) were measured using standard ophthalmologic procedures. Biometric measurements were compared between GJD2 (rs524952) genotype groups; education and environmental risk score (ERS) were calculated to estimate gene-environment interaction effects, using the Synergy index (SI). RESULTS. RS adults carrying two risk alleles had a lower SER and longer AL, ACD and VD (AA versus TT, 0.23D vs. 0.70D; 23.79 mm vs. 23.52 mm; 2.72 mm vs. 2.65 mm; 16.12 mm vs. 15.87 mm; all P &lt; 0.001). Children carrying two risk alleles had larger AL/CR at ages 6 and 9 years (2.88 vs. 2.87 and 3.00 vs. 2.96; all P &lt; 0.001). Education and ERS both negatively influenced myopia and the biometric outcomes, but gene-environment interactions did not reach statistical significance (SI 1.25 [95% confidence interval {CI}, 0.85–1.85] and 1.17 [95% CI, 0.55–2.50] in adults and children). CONCLUSIONS. The elongation of the eye caused by the GJD2 risk genotype follows a dose-response pattern already visible at the age of 6 years. These early effects are an example of how a common myopia gene may drive myopia.</p