Reply Sanfilippo, Paul Gerard; Huynh, Emily; Yazar, Seyhan ...
American journal of ophthalmology,
02/2017, Letnik:
174
Journal Article
Recenzirano
To complicate matters further, there are differences in the measurements obtained by confocal scanning laser tomography (CSLT) compared with those based on Bruch membrane opening (BMO).
Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with ...refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).
Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, ...educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N = 5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P = 1.04 × 10(-3) ). Our estimate of the effect of education on myopia was higher (P = 0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score ∼2 years increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error.
Purpose
To investigate the relationship between time spent outdoors, at particular ages in childhood and adolescence, and myopia status in young adulthood using serum 25‐hydroxyvitamin D 25(OH)D ...concentration as a biomarker of time spent outdoors.
Methods
Participants of the Raine Study Generation 2 cohort had 25(OH)D concentrations measured at the 6‐, 14‐, 17‐ and 20‐year follow‐ups. Participants underwent cycloplegic autorefraction at age 20 years, and myopia was defined as a mean spherical equivalent −0.50 dioptres or more myopic. Logistic regression was used to analyse the association between risk of myopia at age 20 years and age‐specific 25(OH)D concentrations. Linear mixed‐effects models were used to analyse trajectory of 25(OH)D concentrations from 6 to 20 years.
Results
After adjusting for sex, race, parental myopia, body mass index and studying status, myopia at 20 years was associated with lower 25(OH)D concentration at 20 years (per 10 nmol/L decrease, odds ratio (aOR)=1.10, 95% CI: 1.02, 1.18) and a low vitamin D status 25(OH)D < 50 nmol/L at 17 years (aOR = 1.71, 95% CI: 1.06, 2.76) and 20 years (aOR = 1.71, 95% CI: 1.14, 2.56), compared to those without low vitamin D status. There were no associations between 25(OH)D at younger ages and myopia. Individuals who were myopic at 20 years had a 25(OH)D concentration trajectory that declined, relative to non‐myopic peers, with increasing age. Differences in 25(OH)D trajectory between individuals with and without myopia were greater among non‐Caucasians compared to Caucasians.
Conclusions
Myopia in young adulthood was most strongly associated with recent 25(OH)D concentrations, a marker of time spent outdoors.
To evaluate the contribution of genetic and early life environmental factors, as reflected by fetal anthropometric growth trajectories, toward the development of myopia during childhood and ...adolescence.
This analysis included 498 singleton Caucasian participants from the Raine Study, a pregnancy cohort study based in Western Australia. Serial fetal biometric measurements of these participants were collected via ultrasound scans performed at 18, 24, 28, 34, and 38 weeks' gestation. At a 20-year follow-up, the participants underwent a comprehensive ophthalmic examination, including cycloplegic autorefraction and ocular biometry measurements. Using a group-based trajectory modeling approach, we identified groups of participants with similar growth trajectories based on measurements of fetal head circumference (HC), abdominal circumference, femur length (FL), and estimated fetal weight (EFW). Differences between trajectory groups with respect to prevalence of myopia, axial length (AL), and corneal radius of curvature measured at the 20-year follow-up were evaluated via logistic regression and analysis of variance.
Prevalence of myopia was highest among participants with consistently short or consistently long FLs (P = 0.04). There was also a trend toward increased prevalence with larger HC in late gestation, although not at a statistically significant level. Trajectory groups reflecting faster HC, FL, or EFW growth correlated with significantly flatter corneas (P = 0.03, P = 0.04, and P = 0.01, respectively) and a general, but not statistically significant, increase in AL.
Environmental or genetic factors influencing intrauterine skeletal growth may concurrently affect ocular development, with effects persisting into adulthood.
Higher physical working capacity (PWC) at age 17 was associated with thicker peripapillary retinal nerve fiber layer (pRNFL) at age 20, suggesting a mechanistic link between cardiovascular fitness ...and neuroretinal integrity.
Physical activity and cardiovascular fitness has been linked with lower odds of developing glaucoma. We tested the hypothesis that early beneficial effects of physical activity and cardiovascular fitness can be observed by measuring the pRNFL thickness in young healthy adults.
The Raine Study is a longitudinal study that has followed a cohort since before their births in 1989-1992. Parent-reported physical activity was collected between 8 and 17 years, and latent class analysis was used to identify the participants' physical activity trajectories. At the 20-year follow-up (participants' mean age=20.1±0.4 y), participants' metabolic equivalent of task-minutes/week was determined using self-reported physical activity data. Participants' PWC was assessed at the 14- and 17-year follow-ups to estimate their level of cardiovascular fitness. An eye examination, which included spectral-domain optical coherence tomography imaging, was conducted at the 20-year follow-up for 1344 participants.
Parent-reported or participant-reported physical activity was not associated with pRNFL thickness. However, higher PWC at 17 years was associated with thicker pRNFL globally by 0.3 µm; 95% confidence interval (CI)=0.2-0.6; P<0.001, superotemporally (by 0.4 µm; 95% CI=0.1-0.7; P=0.013), inferonasally (by 0.7 µm; 95% CI=0.1-0.9; P=0.002), and nasally (by 0.4 µm; 95% CI=0.1-0.7; P=0.006) per 10 Watt increase in PWC.
The association between estimated cardiovascular fitness and pRNFL thickness suggests there may be overlapping mechanisms for cardiovascular health and retinal ganglion cell integrity. While the effect sizes were small, it is possible that larger effects and clinically significant associations may arise as we follow this cohort of participants through their later adulthood.
Purpose
Cross‐sectional studies have variably reported that poor sleep quality may be associated with myopia in children. Longitudinal data, collected over the ages when myopia develops and ...progresses, could provide new insights into the sleep‐myopia paradigm. This study tested the hypothesis that 12‐year trajectories of sleep behaviour from childhood to adolescence is associated with myopia during young adulthood.
Methods
At the 5‐, 8‐, 10‐, 14‐ and 17‐year follow‐ups of the longitudinal Raine Study, which has been following a cohort since their birth in 1989–1992, participants' parents/guardians completed the Child Behaviour Checklist questionnaire (CBCL), which collected information on their child's sleep behaviour and quality. The CBCL includes six questions measuring sleep behaviour, which parents rated as 0 = not true, 1 = somewhat/sometimes true, or 2 = very/often true. Scores were summed at each follow‐up to form a composite “sleep behaviour score”. Latent Class Growth Analysis (LCGA) was used to classify participants according to their 12‐year trajectory of sleep behaviour. At the 20‐year follow‐up, an eye examination was performed which included cycloplegic autorefraction and axial length measurement.
Results
The LCGA identified three clusters of participants based on their trajectory of sleep behaviour: those with minimal' (43.6% of the total Raine Study sample), ‘declining’ (48.9%), or ‘persistent’ (7.5%) sleep problems. A total of 1194 participants had ophthalmic data and longitudinal sleep data available for analysis (47.2% female, 85.6% Caucasian). No significant differences were observed in regards to age, sex, ethnicity or ocular parameters between trajectory groups. Unadjusted and fully adjusted analyses demonstrated that sleep problem behaviour was not significantly associated with changes in refractive error, axial length or corneal radius.
Conclusions
Our findings do not support the hypothesis that there is an association between sleep behaviour and myopia. Future longitudinal studies should explore sleep trajectory data pre‐ and post‐myopia diagnosis to confirm our results.
To report the prevalence of amblyopia, strabismus, and anisometropia in a young adult population at a single center in Australia and to investigate the underlying prenatal and early-life risk ...factors.
Participants in the Raine Study have been followed from mid-gestation (n = 2,868 newborns) to young adulthood. At age 20 years, 1,344 participants had a comprehensive eye examination, including visual acuity and a detailed orthoptic assessment. Risk factors were determined from medical records and questionnaires completed by the mothers at 18 weeks' gestation. The main outcome measures were the proportions of participants with amblyopia, esotropia, exotropia, or anisometropia (defined as >1 D difference).
Of the 1,125 white participants, 12 (1.1%) had amblyopia, 39 (3.5%) had strabismus, and 33 (2.9%) had anisometropia. In multivariable logistic regression, amblyopia was associated with a maternal history of pregnancy-induced hypertension (OR = 3.80; 95% CI, 1.19-12.13); esotropia, with lower gestational age (OR = 0.97; 95% CI, 0.95-0.97) and a heavier placenta (OR = 1.02; 95% CI, 1.00-1.04); exotropia, with a maternal history of previously treated hypertension (OR = 4.00; 95% CI, 1.06-15.03) and maternal use of recreational drugs during early pregnancy (OR = 3.61; 95% CI, 1.06-15.03); and anisometropia, with older maternal age (OR = 1.07; 95% CI, 1.01-1.14) and an abnormal umbilical cord (OR = 2.39; 95% CI, 1.04-5.47).
The prevalence of amblyopia, strabismus, and anisometropia in this cohort was similar to that in other studies. Preterm birth and maternal health may have adverse effects on eye development.▪
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