Neonatal amygdalae and hippocampi are influenced by genotype and prenatal environment, and reflected in the neonatal DNA methylome.

The amygdala and hippocampus undergo rapid development in early life. The relative contribution of genetic and environmental factors to the establishment of their developmental trajectories has yet to be examined. We performed imaging on neonates and examined how the observed variation in volume and microstructure of the amygdala and hippocampus varied by genotype, and compared with prenatal maternal mental health and socioeconomic status. Gene × Environment models outcompeted models containing genotype or environment only to best explain the majority of measures but some, especially of the amygdaloid microstructure, were best explained by genotype only. Models including DNA methylation measured in the neonate umbilical cords outcompeted the Gene and Gene × Environment models for the majority of amygdaloid measures and minority of hippocampal measures. This study identified brain region-specific gene networks associated with individual differences in fetal brain development. In particular, genetic and epigenetic variation within CUX1 was highlighted.

Posterior Eye Shape Measurement With Retinal OCT Compared to MRI.

PURPOSE: Posterior eye shape assessment by magnetic resonance imaging (MRI) is used to study myopia. We tested the hypothesis that optical coherence tomography (OCT), as an alternative, could measure posterior eye shape similarly to MRI. METHODS: Macular spectral-domain OCT and brain MRI images previously acquired as part of the Singapore Epidemiology of Eye Diseases study were analyzed. The right eye in the MRI and OCT images was automatically segmented. Optical coherence tomography segmentations were corrected for optical and display distortions requiring biometry data. The segmentations were fitted to spheres and ellipsoids to obtain the posterior eye radius of curvature (Rc) and asphericity (Qxz). The differences in Rc and Qxz measured by MRI and OCT were tested using paired t-tests. Categorical assignments of prolateness or oblateness using Qxz were compared. RESULTS: Fifty-two subjects (67.8 ± 5.6 years old) with spherical equivalent refraction from +0.50 to -5.38 were included. The mean paired difference between MRI and original OCT posterior eye Rc was 24.03 ± 46.49 mm (P = 0.0005). For corrected OCT images, the difference in Rc decreased to -0.23 ± 2.47 mm (P = 0.51). The difference between MRI and OCT asphericity, Qxz, was -0.052 ± 0.343 (P = 0.28). However, categorical agreement was only moderate (κ = 0.50). CONCLUSIONS: Distortion-corrected OCT measurements of Rc and Qxz were not statistically significantly different from MRI, although the moderate categorical agreement suggests that individual differences remained. This study provides evidence that with distortion correction, noninvasive office-based OCT could potentially be used instead of MRI for the study of posterior eye shape.

Impact of glaucoma severity and laterality on vision-specific functioning: the Singapore Malay eye study.

PURPOSE: We determined the impact of glaucoma severity and laterality on vision-specific functioning (VF) in an Asian population. METHODS: The Singapore Malay Eye Study (SiMES) was a population-based cross-sectional study of 3280 Malays aged 40 to 80 years. VF was assessed using the VF-11 questionnaire. Associations between VF-11 score and glaucoma clinical indices (glaucoma severity in better and worse eyes, and laterality) were determined by multivariate regression modeling. Glaucoma severity was defined as mild, moderate, advanced, and severe based on the Hodapp-Anderson-Parish system. Rasch analysis was used to validate the VF-11 and determine its psychometric properties. RESULTS: Of 926 persons analyzed, 123 had glaucoma (13.3% glaucoma prevalence in analyzed sample). The mean ± SD VF score was 3.64 ± 1.05 log of odds units (Logits). In multivariate models adjusting for sociodemographic, ocular, and systemic variables, poorer VF was associated with increasingly worse eye visual field loss (ß = 0.016, 95% confidence interval [CI] 0.004-0.029, P < 0.001), but not that of the better eye (P > 0.05). Compared to controls, VF was reduced in individuals with worse eye advanced and severe glaucoma (ß = -0.65, 95% CI -1.03 to -0.28, P < 0.05), but not mild or moderate glaucoma (P > 0.05). Compared to controls, VF was reduced in unilateral (ß = -0.29, 95% CI -0.54 to -0.04, P < 0.05), but not bilateral glaucoma (P > 0.05). These associations remained significant after adjusting for presenting and best-corrected visual acuity. CONCLUSIONS: Among Singaporean Malays, unilateral, and advanced and severe glaucoma in the worse eye significantly impacts on VF. Identifying early-stage glaucoma, preventing progression, and visual rehabilitation in advanced glaucoma are important aspects of glaucoma management.

Childhood Vascular Risk Factors and Retinal Vessel Caliber.

PURPOSE: Variations in retinal vessel caliber have been associated with risk of ocular and systemic vascular diseases in adults. In this study, we examined the relationships between childhood vascular risk factors and retinal vessel caliber in young healthy adolescents. DESIGN: This was a cross-sectional study of 1225 adolescents recruited from 3 community-based schools in Singapore. METHODS: Blood pressure and anthropometry measurements were obtained through standardized examinations. Birth weight was ascertained from health records completed by medical personnel soon after birth. Retinal vessel caliber was measured from retinal photographs using a semiautomated computer-based program following a validated standardized protocol. RESULTS: After adjusting for age, sex, and other relevant factors, each SD increase in blood pressure levels (systolic or diastolic) was associated with narrower arteriolar caliber (1.61 µm; P < 0.001); each SD increase in body mass index was associated with narrower arteriolar caliber (1.49 µm; P < 0.001) and wider venular caliber (2.68 µm; P < 0.001), and each SD decrease in birth weight was associated with narrower arteriolar caliber (1.31 µm; P = 0.001). CONCLUSIONS: Young adolescents with elevated blood pressure, obesity, or low birth weight have changes in retinal vessel caliber that are associated with ocular and systemic vascular diseases in adulthood. These findings provide evidence of possible adverse effects of childhood vascular risk factors on the retinal microvasculature early in life.

Quantitative and qualitative retinal microvascular characteristics and blood pressure.

OBJECTIVE: The present study examined the effects of blood pressure on a spectrum of quantitative and qualitative retinal microvascular signs. METHODS: Retinal photographs from the Singapore Malay Eye Study, a population-based cross-sectional study of 3280 (78.7% response) persons aged 40-80 years, were analyzed. Quantitative changes in the retinal vasculature (branching angle, vascular tortuosity, fractal dimension, and vascular caliber) were measured using a semi-automated computer-based program. Qualitative signs, including focal arteriolar narrowing (FAN), arteriovenous nicking (AVN), opacification of the arteriolar wall (OAW), and retinopathy (e.g., microaneurysms, retinal hemorrhages), were assessed from photographs by trained technicians. After excluding persons with diabetes and ungradable photographs, 1913 persons provided data for this analysis. RESULTS: In multivariable linear regression models controlling for age, sex, BMI, use of antihypertensive medication, and other factors, retinal arteriolar branching asymmetry ratio, arteriolar tortuosity, venular tortuosity, fractal dimension, arteriolar caliber, venular caliber, FAN, AVN, and retinopathy were independently associated with mean arterial blood pressure. In contrast, arteriolar/venular branching angle, venular branching asymmetry ratio and OAW were not related to blood pressure. Retinal arteriolar caliber (sß = -0.277) and FAN (sß = 0.170) had the strongest associations with mean arterial blood pressure, and higher blood pressure levels were associated with increasing number of both quantitative and qualitative retinal vascular signs (P trend <0.001). CONCLUSION: Elevated blood pressure is associated with a spectrum of quantitative and qualitative retinal vascular signs, with the number of signs increasing with higher blood pressure levels.

Prevalence and risk factors of ocular trauma in an urban south-east Asian population: the Singapore Malay Eye Study.

PURPOSE: To describe the prevalence and risk factors of ocular trauma in an urban Asian population. METHODS: A population-based survey of 3280 (78.7% response rate) Malay people aged 40-80 years residing in Singapore was conducted in 2004-2006. Interviewer-administered questionnaire was used to ascertain a history of ocular trauma, defined as any eye injury requiring medical attention from a doctor. RESULTS: Of the 3264 participants, 149 (5.0%, 95% confidence intervals [CI] 4.1-6.0%) reported a history of ocular trauma. Of those, 30.2% had trauma from a blunt object, 33.6% from a sharp object, and 22.1% from chemical burns. After adjusting for age and sex, men had a higher prevalence of ocular trauma than women (8.3% vs. 2.1%, age-adjusted odds ratio [OR] 4.7, CI 3.1-7.1), and younger persons had a higher risk of ocular trauma (per year increase in age, OR 0.98, CI 0.96-0.99). Consumption of alcohol was associated with higher likelihood of having ocular injury (OR 4.3, CI 2.2-8.4). CONCLUSIONS: One in 20 persons in this urban south-east Asian population had a history of ocular trauma. Younger persons, men and consumption of alcohol were risk factors for ocular trauma.

Relationships of retinal vessel diameters with optic disc, macular and retinal nerve fiber layer parameters in 6-year-old children.

PURPOSE: To describe the normal anatomic relationships of retinal vessel diameters with optic disc, macula, and retinal nerve fiber layer parameters in young children. METHODS: This was a population-based, cross-sectional study of 1204 healthy children 6 years of age who were participating in the Sydney Childhood Eye Study. Retinal arteriolar and venular diameters were measured from fundus photographs using standardized computer-based methods. Optical coherence tomography was performed to obtain measurements of the optic disc, macula, and retinal nerve fiber layer parameters. RESULTS: In multivariate analyses, each standard deviation (SD) decrease in optic disc area was associated with a 0.14-pixel decrease (P = 0.05) in arteriolar diameter and a 0.31-pixel decrease (P < 0.01) in venular diameter. Each SD decrease in optic cup area was associated with a 0.15-pixel decrease (P = 0.05) in arteriolar diameter and a 0.43-pixel decrease (P < 0.01) in venular diameter. Each SD decrease in macular (inner/outer) thickness or volume was associated with a 0.25- to 0.39-pixel decrease (P < 0.01) in arteriolar diameter and a 0.36- to 0.71-pixel decrease (P < 0.01) in venular diameter, and each SD decrease in retinal nerve fiber layer thickness was associated with a 0.62-pixel decrease (P < 0.01) in arteriolar diameter and a 0.99-pixel decrease (P < 0.01) in venular diameter. CONCLUSIONS: Children's eyes with a smaller optic disc, thinner macula, and thinner retinal nerve fiber layer have narrower retinal vessels. These anatomic relationships may provide new insights into the vascular etiology of various ocular diseases.

Distribution and associations of retinal vascular caliber with ethnicity, gender, and birth parameters in young children.

PURPOSE: To describe the distribution of retinal vascular calibers and their associations with ethnicity, gender, and birth parameters in children. METHODS: This was a school-based cross-sectional study of 768 children aged 7 to 9 years who participated in the Singapore Cohort Study of the Risk Factors for Myopia (SCORM). Participants had retinal photographs taken in 2001. Retinal vascular calibers were measured with computer-based program and summarized as average caliber of arterioles and venules in that eye. Associations of retinal vascular caliber with ethnicity, gender, and various birth factors were analyzed. RESULTS: In this population, the mean retinal arteriolar caliber was 156.4 microm (95% confidence interval [CI], 155.4-157.3) and venular caliber was 225.4 microm (95% CI, 224.1-226.8). The retinal arteriolar caliber was significantly narrower in Chinese (154.9 microm), compared with Malay (158.6 microm) and Indian (158.5 microm) children. Retinal venular caliber was also narrower in Chinese (223.3 microm) compared with Malay (230.8 microm) and Indian (229.0 microm) children. These differences were statistically significant, even after adjustments for age, gender, family income, parental education, body mass index, height, birth weight, axial length, and spherical equivalent (P = 0.05 for arteriolar caliber; P = 0.002 for venular caliber). In multivariate analysis, there were no significant gender differences in retinal vascular caliber. Birth factors, including birth weight, birth length, head circumference, and gestational age, were not significantly associated with changes in either retinal arteriolar or venular caliber. CONCLUSIONS: The results show ethnic variation in retinal vascular caliber in Singaporean children. No association of birth parameters with retinal vascular caliber was found. Because retinal vascular caliber is related to various cardiovascular and ocular diseases, it is possible that ethnic variations in retinal vascular caliber should be taken into consideration in future studies.

Prevalence of cataract in rural Indonesia.

PURPOSE: To describe the prevalence of cataract in adults in rural Sumatra, Indonesia. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A random sample of all adults aged 21 years or older living in 3 rural villages in central Sumatra was assessed. Nine hundred nineteen of 1089 (84.4%) eligible adults participated. METHODS: A team of 7 ophthalmologists examined the anterior segment of both eyes using a portable slit lamp after pupil dilatation. Lens opacity was graded according to the Lens Opacities Classification System III (LOCS III). A structured questionnaire was used to collect data on education level and income. MAIN OUTCOME MEASURES: Cataract was defined as either a LOCS III nuclear region score of > or =4.0, cortical > or =4.0, or posterior subcapsular (PSC) cataract > or =2.0, in either eye. RESULTS: Two hundred one (21.9%) of 919 subjects were found to have cataract. The age-adjusted prevalence rate of cataract (including cataract surgery) was 23.0% (95% confidence interval, 20.8-25.2). The most common type of cataract for both genders (adjusted for age) was mixed (13%) followed by nuclear only (5.7%), and cortical only (4%). The prevalence rate of any cataract for adults aged 21 to 29 was 1.1%, increasing to 82.8% for those aged older than 60 years. Similar trends with age were noted for nuclear, cortical, and PSC cataract. Women had higher prevalence rates than men for all types of cataract except cortical. There was a trend of increasing prevalence of all types of cataract with decreasing education (P<0.001). CONCLUSIONS: Cataract prevalence in adults aged 21 years and older in rural Indonesia is among the highest reported in Southeast Asia. Despite this, there are inadequate resources available to manage this treatable disease. Allocation of resources to tackle the present burden of cataract would likely have large personal, social, and economic benefits.

Prevalence of stroke among Chinese, Malay, and Indian Singaporeans: a community-based tri-racial cross-sectional survey.

BACKGROUND AND PURPOSE: Stroke prevalence data among mixed Asian populations are lacking. Prevalence rates of stroke were studied among Singaporeans aged > or =50 years of Chinese, Malay, and Indian origin. METHODS: Study participants were selected by disproportionate stratified random sampling by race. Trained interviewers performed face-to-face interviews with subjects using the World Health Organization screening protocol for neurological diseases. Data were also collected on a self-report of stroke. Subjects suspected to have had a stroke underwent a clinical evaluation to diagnose or exclude stroke. Case notes review was performed for those who were unable to come for clinical evaluation. RESULTS: The study involved 14 906 participants: 6734 men, 8172 women, age range 52 to 106 years, Chinese:Malay:Indian ratio 3:1:1. Participation rate was 66.9%. Six hundred and six were diagnosed to have a stroke, yielding a crude prevalence rate of 4.05% (95% CI, 3.75 to 4.38) and a World Health Organization world population age-gender-standardized rate of 3.65% (95% CI, 3.36 to 3.96). Prevalence rates rose with age (P<0.001 for trend) and were higher among men compared with women, 4.53% (95% CI, 4.05 to 5.07) versus 2.91% (95% CI, 2.57 to 3.29), P<0.01. Age and gender-standardized rates among Chinese, Malays, and Indians were 3.76% (95% CI, 3.38 to 4.17), 3.32 (95% CI, 2.72 to 4.07), and 3.62% (95% CI, 2.95 to 4.44), respectively, P>0.2. Prevalence was highest among Chinese men at 4.78% (95% CI, 4.14 to 5.50) and lowest among Malay women at 2.81% (95% CI, 2.08 to 3.81), P=0.01. CONCLUSIONS: There is no difference in stroke prevalence among Chinese, Malay, and Indian Singaporeans. Prevalence is highest among Chinese men and lowest among Malay women. The reasons for these differences warrant further investigation.