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.

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 increased with increasing body height (1.3 µm/cm, 95% CI 0.8 to 1.9, p < 0.001). Additionally, choroidal thickness increased with increasing birthweight (13.0 µm/kg; 95% CI 0.006-0.020; p < 0.001) and increasing size for gestational age (8.2 µm/kg; 95% CI 4.6-11.8; p < 0.001). Smoking up until the time that pregnancy became known was associated with a thinner choroid (p = 0.016). There was no detectable effect of alcohol consumption. The distributions of axial length, refraction and choroidal thickness were narrower than in older populations. CONCLUSION: The subfoveal choroid was thicker in girls than in boys, and higher body height, higher birthweight and larger size for gestational age were associated with a thicker subfoveal choroid. The implications of these findings for myopia development need further evaluation in longitudinal studies.

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 (ß 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.

Interaction between lifestyle and genetic susceptibility in myopia: the Generation R study.

Myopia is a refractive error of the eye caused by a complex interplay between nature and nurture. The aim of this study was to investigate whether environmental risk factors can influence the genetic effect in children developing myopia. A total of 3422 children participating in the birth-cohort study Generation R underwent an extensive eye examination at 9 years with measurements of refractive error and axial length corneal radius ratio (AL/CR). Environmental risk factors were evaluated using a questionnaire, and environmental risk scores (ERS) were calculated using backward regression analyses. Genetic risk scores (GRS) were calculated based on all currently known risk variants for myopia. Gene-environment interaction (G×E) was investigated using linear and logistic regression analyses. The predictive value of G×E and parental myopia was estimated using receiver operating characteristic curves. Myopia prevalence was 12%. Both GRS (P < 0.01) and ERS (P < 0.01) were significantly associated with myopia and AL/CR, as was G×E interaction (P < 0.01 for myopia; P = 0.07 for AL/CR). The predictive value of parental myopia was 0.67 (95% CI 0.65-0.70), similar to the values of GRS (0.67; 95% CI 0.64-0.70; P = 0.98) and ERS (0.69; 95% CI 0.66-0.72; P = 0.98). Adding G×E interaction significantly improved the predictive value to 0.73 (95% CI 0.70-0.75; P < 0.01). This study provides evidence that nature and nurture are equally important for myopia and AL/CR; however, the combination has the strongest influence. Since myopia genes are common in the population, adjustment of lifestyle should be a major focus in the prevention of myopia.

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.