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Myopic traction maculopathy (MTM), one of the complications of pathologic myopia, is a spectrum of pathological conditions that are attributed to tractional changes in the eye characterized by retinoschisis, lamellar or full thickness macular hole, and foveal retinal detachment. Considering the global public health burden of MTM and pathologic myopia, it is important to understand these sight-threatening complications and their associations. We conducted an evidence-based review of the prevalence and natural history of MTM and associated risk factors. The prevalence of MTM in the general population is low, but is increased among high myopes. MTM is associated with preretinal tractional structures, myopic refractive error and axial elongation, posterior staphyloma, dome-shaped macula, chorioretinal atrophy, and myopic macular degeneration. The clinical course of MTM tends to be stable; however, MTM may progress, resulting in visual acuity deterioration, although spontaneous improvement also occurs. The associations of MTM progression include vitreous traction, location, and extent of MTM, and lamellar macular hole-specific factors. More high-quality population-based studies that assess MTM prevalence and natural history are needed.

To evaluate the transancestry portability of current myopia polygenic risk scores (PRSs) to predict high myopia (HM) and myopic macular degeneration (MMD) in an Asian population.Population-based study.A total of 5894 adults (2141 Chinese, 1913 Indian, and 1840 Malay) from the Singapore Epidemiology of Eye Diseases study were included in the analysis. The mean ± standard deviation age was 57.05 ± 9.31 years. A total of 361 adults had a diagnosis of HM (spherical equivalent [SE]-5.00 diopters [D]) from refraction measurements, 240 individuals had a diagnosis of MMD graded by the International Photographic Classification and Grading System for Myopic Maculopathy criteria from fundus photographs, and 3774 individuals were control participants without myopia (SE-0.5 D).The PRS, derived from 687 289 HapMap3 single nucleotide polymorphisms (SNPs) from the largest genome-wide association study of myopia in Europeans to date (n = 260 974), was assessed on its ability to predict patients with HM and MMD versus control participants.The primary outcomes were the area under the receiver operating characteristic curve (AUC) to predict HM and MMD.The PRS had an AUC of 0.73 (95% confidence interval [CI], 0.70-0.75) for HM and 0.66 (95% CI, 0.63-0.70) for MMD versus no myopia. The inclusion of the PRS with other predictors (age, sex, educational attainment [EA], and ancestry; age-by-ancestry, sex-by-ancestry, and EA-by-ancestry interactions; and 20 genotypic principal components) increased the AUC to 0.84 (95% CI, 0.82-0.86) for HM and 0.79 (95% CI, 0.76-0.82) for MMD. Individuals with a PRS in the top 5% showed up to a 4.66 (95% CI, 3.34-6.42) times higher risk of HM developing and up to a 3.43 (95% CI, 2.27-5.05) times higher risk of MMD developing compared with the remaining 95% of individuals.The PRS is a good predictor for HM and facilitates the identification of high-risk children to prevent myopia progression to HM. In addition, the PRS also predicts MMD and helps to identify high-risk adults with myopia who require closer monitoring for myopia-related complications.

Purpose To determine whether eyes with pathologic myopia can be identified and whether each type of myopic maculopathy lesion on fundus photographs can be diagnosed by deep learning (DL) algorithms. Design A DL algorithm was developed to recognize myopic maculopathy features and to categorize the myopic maculopathy automatically. Participants We examined 7020 fundus images from 4432 highly myopic eyes obtained from the Advanced Clinical Center for Myopia. Methods Deep learning (DL) algorithms were developed to recognize the key features of myopic maculopathy with 5176 fundus images. These algorithms were also used to develop a Meta-analysis for Pathologic Myopia (META-PM) study categorizing system (CS) by adding a specific processing layer. Models and the system were evaluated by 1844 fundus image. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to determine the performance of each DL algorithm. The rate of correct predictions was used to determine the performance of the META-PM study CS. Main Outcome Measures Four trained DL models were able to recognize the lesions of myopic maculopathy accurately with high sensitivity and specificity. The META-PM study CS also showed a high accuracy and was qualified to be used in a semiautomated way during screening for myopic maculopathy in highly myopic eyes. Results The sensitivity of the DL models was 84.44% for diffuse atrophy, 87.22% for patchy atrophy, 85.10% for macular atrophy, and 37.07% for choroidal neovascularization, and the AUC values were 0.970, 0.978, 0.982, and 0.881, respectively. The rate of total correct predictions from the META-PM study CS was 87.53%, with rates of 90.18%, 95.28%, 97.50%, and 91.14%, respectively, for each type of lesion. The META-PM study CS showed an overall rate of 92.08% in detecting pathologic myopia correctly, which was defined as having myopic maculopathy equal to or more serious than diffuse atrophy. Conclusions The novel DL models and system can achieve high sensitivity and specificity in identifying the different types of lesions of myopic maculopathy. These results will assist in the screening for pathologic myopia and subsequent protection of patients against low vision and blindness caused by myopic maculopathy.

Purpose To identify novel susceptibility loci for high myopia. Design Genome-wide association study (GWAS) followed by replication and meta-analysis. Participants A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). Methods We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. Main Outcome Measures We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. Results We identified 9 loci with genome-wide significance (P Conclusions The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.

Highly myopic Singaporean children progress rapidly by adolescence to their adult spherical equivalent, with early onset and baseline myopia associated with pathologic findings of thinner choroid and tessellated fundus in young adulthood.

Purpose To describe the prevalence, ocular characteristics, and associated risk factors of moderate to high hyperopia in early childhood. Design Pooled analysis of individual participant data from population-based studies. Participants Six- to 72-month-old multiethnic children who participated in 4 population-based studies of pediatric eye diseases. Methods The pooled studies conducted comparable parental interviews and ocular examinations including cycloplegic autorefraction. Presence of hyperopia was defined based on cycloplegic refractive error in the worse eye. Multivariate analyses were performed to evaluate the association of potential risk factors with hyperopia risk. Main Outcome Measures Prevalence and odds ratios of moderate to high hyperopia (≥4.0 diopters [D]). Results Cycloplegic refraction was completed in 15 051 children 6 to 72 months of age. Among these children, the overall prevalence of moderate to high hyperopia (≥4.0 D) in the worse eye was 3.2% (95% confidence interval, 2.9%–3.5%), accounting for 15.6% of all hyperopia (≥2.0 D). Among children with moderate to high hyperopia, both eyes were affected in 64.4%, 28.9% showed spherical anisometropia of 1.0 D or more, and 19.5% showed astigmatism of 1.5 D or more. Among 36- to 72-month-old children with moderate to high hyperopia, 17.6% wore glasses. Prevalence of moderate to high hyperopia was slightly less in 12- to 23-month-old children and was relatively stable in children 24 months of age and older. Non-Hispanic and Hispanic white race and ethnicity, family history of strabismus, maternal smoking during pregnancy, and being a participant in the United States studies were associated with a higher risk of moderate to high hyperopia (P Conclusions By assembling similarly designed studies, our consortium provided robust estimates of the prevalence of moderate to high hyperopia in the general population and showed that in 6- to 72-month-old children, moderate to high hyperopia is not uncommon and its prevalence does not decrease with age. Risk factors for moderate to high hyperopia differ from those for low to moderate hyperopia (2.0–

At the time of publication the author Jyn Ling Kuan did not have a master's degree; this has now been amended to BSc. This has now been corrected in the PDF and HTML versions of the article.

Purpose There is a limited understanding of ocular risk factors for diabetic retinopathy (DR). Our aim therefore was to determine the relationship of 2 retinal signs related to axial myopia (peripapillary atrophy [PPA] and fundus tessellation) with DR. Design Cross-sectional study. Methods Of 3353 subjects (72.8% response rate) who participated in the population-based Singapore Chinese Eye Study, 592 participants had diabetes. Of these, 1010 eyes from 530 participants were included in our analyses after excluding participants without gradable retinal photographs or missing key variables. DR, PPA-beta (β), and fundus tessellation were graded from retinal photographs. The associations between PPA-β or fundus tessellation with DR were analyzed using logistic regression models with generalized estimating equations. Main Outcome Measures Diabetic retinopathy. Results Among the 530 participants, the mean (standard deviation) age was 62.8 (9.2) years, and 288 (54.3%) were male. PPA-β and fundus tessellation were both associated with longer axial length (AL). In multivariable analyses adjusting for potential confounders including AL, eyes with PPA-β or fundus tessellation were less likely to have any DR, with odds ratio (95% confidence interval) 0.58 (0.41–0.83) and 0.46 (0.25–0.87), respectively. These associations with DR were consistent in models adjusting for refractive status, and in a subanalysis that excluded eyes with high AL (>24.5 mm). Conclusions Eyes with PPA-β or fundus tessellation were less likely to have DR, independent of diabetes risk factors, AL, or refractive status. The presence of these 2 ophthalmic features may indicate lower risk of DR.

Despite claims concerning biological mechanisms sub-serving infant attention, little experimental work examines its underpinnings. This study examines how candidate polymorphisms from the cholinergic ( CHRNA4 rs1044396) and dopaminergic ( COMT rs4680) systems, respectively indicative of parietal and prefrontal/anterior cingulate involvement, are related to 6-month-olds’ ( n = 217) performance during a visual expectation eye-tracking paradigm. As previous studies suggest that both cholinergic and dopaminergic genes may influence susceptibility to the influence of other genetic and environmental factors, we further examined whether these candidate genes interact with one another and/or with early caregiving experience in predicting infants’ visual attention. We detected an interaction between CHRNA4 genotype and observed maternal sensitivity upon infants’ orienting to random stimuli and a CHRNA4 - COMT interaction effect upon infants’ orienting to patterned stimuli. Consistent with adult research, we observed a direct effect of COMT genotype on anticipatory looking to patterned stimuli. Findings suggest that CHRNA4 genotype may influence susceptibility to other attention-related factors in infancy. These interactions may account for the inability to establish a link between CHRNA4 and orienting in infant research to date, despite developmental theorizing suggesting otherwise. Moreover, findings suggest that by 6 months, dopamine, and relatedly, the prefrontal cortex/anterior cingulate, may be important to infant attention.

To evaluate the relationship between both spherical equivalent (SE) and retinal thickness (RT) on best-corrected visual acuity (BCVA) among young Asian adult men under photopic, mesopic, and simulated night-vision goggle (NVG) lighting conditions.Community-based cross-sectional study.Total of 698 myopic and 148 emmetropic subjects.All participants underwent a complete ophthalmic examination and color fundus photography. BCVA and subjective refraction were assessed under standardized photopic, mesopic, and simulated NVG lighting conditions. Retinal thickness in various Early Treatment Diabetic Retinopathy Study (ETDRS) subfields was measured using spectral-domain OCT using a standardized protocol. Univariate and multiple linear regression analyses were performed to assess the relationship between BCVA and both SE and RT.Relationship between BCVA and both SE and RT.The mean age of all subjects was 21.1 years, with mean SE of -8.44 diopter (D) among the myopic subjects (range, -3.75 D to -23.0 D) and +0.10 among the emmetropic subjects (range, -0.49 D to +1.00 D). BCVA worsened progressively with increasing myopia under all lighting conditions (standardized coefficient -0.581 under photopic conditions, P0.001). RT was thickest among participants with LogMAR VA ≤0.00, and became thinner in the groups including those with VA0.00 to ≤0.10 and0.10 (mean inner subfield RT: 342.7 μm vs. 338.1 μm vs. 331.0 μm, respectively, P0.001) under all lighting conditions. When multiple linear regression was performed, higher degrees of myopia and decreasing RT were associated with reduced BCVA (all P0.05). For each diopter increase in myopia, mean BCVA decreased by 0.01 LogMAR in photopic conditions and 0.02 LogMAR in mesopic conditions (both P0.001). The mean BCVA reduced by 0.05 LogMAR (P = 0.003) and 0.04 LogMAR (P = 0.037), under photopic and scotopic lighting conditions respectively, for each 100-μm decrease in RT.Both the severity of myopia and macular RT independently affect visual performance under photopic, mesopic, and simulated NVG conditions.

Background: Dietary protein may affect glucose metabolism through several mechanisms, but results from studies on dietary protein intake and risk of gestational diabetes mellitus (GDM) have been inconsistent.Objective: We examined the cross-sectional associations of dietary protein intake from different food sources during pregnancy with the risk of GDM in a multiethnic Asian population.Methods: We included 980 participants with singleton pregnancies from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort. Protein intake was ascertained from 24-h dietary recall and 3-d food diaries at 26-28 wk gestation. GDM was defined as fasting glucose ≥7.0 mmol/L and/or 2-h postload glucose ≥7.8 mmol/L at 26-28 wk gestation. We evaluated the association of dietary protein intake with GDM risk by substituting carbohydrate with protein in an isocaloric model with the use of multivariable logistic regression analysis.Results: The prevalence of GDM was 17.9% among our participants. After adjustment for potential confounders, a higher total dietary protein intake was associated with a higher risk of GDM; the OR comparing the highest with the lowest quartile of intake was 2.15 (95% CI: 1.27, 3.62; P-trend = 0.016). Higher intake levels of both animal protein (OR: 2.87; 95% CI: 1.58, 5.20; P-trend = 0.001) and vegetable protein (OR: 1.78; 95% CI: 0.99, 3.20; P-trend = 0.009) were associated with a higher risk of GDM. Among the animal protein sources, higher intake levels of seafood protein (OR: 2.17; 95% CI: 1.26, 3.72; P-trend = 0.023) and dairy protein (OR: 1.87; 95% CI: 1.11, 3.15; P-trend = 0.017) were significantly associated with a higher GDM risk.Conclusion: Higher intake levels of both animal and vegetable protein were associated with a higher risk of GDM in Asian women. This trial was registered at clinicaltrials.gov as NCT01174875.

Background Maternal dietary patterns during pregnancy have been shown to influence infant birth outcomes. However, to our knowledge, only a few studies have examined the associations in Asian populations. Objective We characterized maternal dietary patterns in Asian pregnant women and examined their associations with the risk of preterm birth and offspring birth size. Design At 26-28 wk of gestation, 24-h recalls and 3-d food diaries were collected from the women in the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort. Dietary patterns were derived from exploratory factor analysis. Gestational age was determined by a dating ultrasound scan in the first trimester, and infant birth anthropometric measurements were obtained from hospital records. Associations were assessed by logistic and linear regressions with adjustment for confounding factors. Results Three maternal dietary patterns were identified: vegetable, fruit, and white rice (VFR); seafood and noodle (SfN); and pasta, cheese, and processed meat (PCP). Of 923 infants, 7.6% were born preterm, 13.4% were born small for gestational age, and 14.7% were born large for gestational age. A greater adherence to the VFR pattern (per SD increase in VFR score) was associated with a lower risk of preterm births (OR: 0.67; 95% CI: 0.50, 0.91), higher ponderal index (β: 0.26 kg/m3; 95% CI: 0.06, 0.45 kg/m3), and increased risk of a large-for-gestational-age birth (RR: 1.31; 95% CI: 1.06, 1.62). No associations were observed for the SfN and PCP patterns in relation to birth outcomes. Conclusions The VFR pattern is associated with a lower incidence of preterm birth and with larger birth size in an Asian population. The findings related to larger birth size warrant further confirmation in independent studies. This trial was registered at clinicaltrials.gov as NCT01174875.

Background: Infant body composition has been associated with later metabolic risk, but few studies have examined the association between maternal macronutrient intake and neonatal body composition. Furthermore, most of those studies have used proxy measures of body composition that may not reflect body fat distribution, particularly abdominal internal adiposity. Objective: We investigated the relation between maternal macronutrient intake and neonatal abdominal adiposity measured using magnetic resonance imaging (MRI) in a multi-ethnic Asian mother-offspring cohort. Methods: Macronutrient intakes of mothers were ascertained using a 24-h dietary recall at 26-28 weeks gestation. Neonatal abdominal adiposity was assessed using MRI in the second week of life. Mother-offspring dyads with complete macronutrient intake and adiposity information (n= 320) were included in the analysis. Associations were assessed by both substitution and addition models using multivariable linear regressions. Results: Mothers [mean age: 30 y; 44% Chinese, 38% Malay, 18% Indians] consumed 15.5 ± 4.3% (mean ± SD) of their energy intakes from protein, 32.4 ± 7.7% from fat, and 52.1 ± 9.0% from carbohydrate. A higher protein, lower carbohydrate/fat diet during pregnancy was associated with lower abdominal internal adipose tissue (IAT) in the neonates [? (95% CI): -0.18 (-0.35, -0.001) mL per 1% protein to carbohydrate substitution and -0.25 (-0.46, -0.04) mL per 1% protein to fat substitution]. These associations were stronger in boys than in girls (P-interactions Conclusions: Higher maternal protein intake (at the expense of carbohydrate or fat intake) at 26-28 wk of gestation was associated with lower abdominal internal adiposity in neonates. Optimizing maternal dietary balance might be a new approach to potentially improve offspring body composition.

The influence of circadian feeding patterns on weight outcomes has been shown in animal and human studies but not in very young children.We aimed to examine the association of infant circadian feeding patterns at 12 mo of age with subsequent growth and weight status after 1 y.Mothers from a Singapore birth cohort (n = 349) reported the food given to their infants and the feeding time at 12 mo of age. Predominantly daytime (pDT) (0700-1859; n = 282) and predominantly nighttime (pNT) (1900-0659; n = 67) feeding infants were defined by whether daytime energy intake was50% or50% of total energy intake as assessed with the use of a 24-h recall. Body mass index-for-age z scores (BAZs) were computed with the use of the WHO Child Growth Standards 2006 to determine changes in BAZs from 12 to 24 mo of age and weight status at 24 mo of age. Multivariable linear and logistic regression analyses were performed.Compared with pDT feeding, pNT feeding was associated with a higher BAZ gain from 12 to 24 mo of age (adjusted β = 0.38; 95% CI: 0.11, 0.65; P = 0.006) and increased risk of becoming overweight at 24 mo of age (adjusted OR: 2.78; 95% CI: 1.11, 6.97; P = 0.029) with adjustments for maternal age, education, ethnicity, monthly household income, parity, infant BAZ at 12 mo of age, feeding mode in the first 6 mo of life, and total daily energy intake.Our study suggests that the role of the daily distribution of energy consumption in weight regulation begins in infancy. The feeding of infants predominantly during nighttime hours was associated with adiposity gain and risk of overweight in early childhood. The inclusion of advice on the appropriate feeding time may be considered when implementing strategies to combat childhood obesity. This trial was registered at clinicaltrials.gov as NCT01174875.

Background: A susceptibility to metabolic diseases is associated with abdominal adipose tissue distribution and varies between ethnic groups. The distribution of abdominal adipose tissue at birth may give insights into whether ethnicity-associated variations in metabolic risk originate partly in utero. Objective: We assessed the influence of ethnicity on abdominal adipose tissue compartments in Asian neonates in the Growing Up in Singapore Toward Healthy Outcomes mother-offspring cohort. Design: MRI was performed at #2 wk after birth in 333 neonates born at $34 wk of gestation and with birth weights $2000 g. Abdominal superficial subcutaneous tissue (sSAT), deep subcutaneous tissue (dSAT), and internal adipose tissue (IAT) compartment volumes (absolute and as a percentage of the total abdominal volume) were quantified. Results: In multivariate analyses that were controlled for sex, age, and parity, the absolute and percentage of dSATand the percentage of sSAT (but not absolute sSAT) were greater, whereas absolute IAT (but not the percentage of IAT) was lower, in Indian neonates than in Chinese neonates. Compared with Chinese neonates, Malay neonates had greater percentages of sSAT and dSAT but similar percentages of IAT. Marginal structural model analyses largely confirmed the results on the basis of volume percentages with controlled direct effects of ethnicity on abdominal adipose tissue; dSAT was significantly greater (1.45 mL; 95% CI: 0.49, 2.41 mL, P = 0.003) in non-Chinese (Indian or Malay) neonates than in Chinese neonates. However, ethnic differences in sSAT and IAT were NS [3.06 mL (95% CI:20.27, 6.39 mL; P = 0.0712) for sSAT and 21.30 mL (95% CI: 22.64, 0.04 mL; P = 0.057) for IAT in non-Chinese compared with Chinese neonates, respectively]. Conclusions: Indian and Malay neonates have a greater dSAT volume than do Chinese neonates. This finding supports the notion that in utero influences may contribute to higher cardiometabolic risk observed in Indian and Malay persons in our population. If such differences persist in the longitudinal tracking of adipose tissue growth, these differences may contribute to the ethnic disparities in risks of cardiometabolic diseases. This trial was registered at clinicaltrials.gov as NCT01174875. Am J Clin Nutr doi: 10.3945/ajcn.115.108738.

Purpose To determine the effectiveness of different interventions to slow down the progression of myopia in children. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov from inception to August 2014. We selected randomized controlled trials (RCTs) involving interventions for controlling the progression of myopia in children with a treatment duration of at least 1 year for analysis. Main Outcome Measures The primary outcomes were mean annual change in refraction (diopters/year) and mean annual change in axial length (millimeters/year). Results Thirty RCTs (involving 5422 eyes) were identified. Network meta-analysis showed that in comparison with placebo or single vision spectacle lenses, high-dose atropine (refraction change: 0.68 [0.52–0.84]; axial length change: −0.21 [−0.28 to −0.16]), moderate-dose atropine (refraction change: 0.53 [0.28–0.77]; axial length change: −0.21 [−0.32 to −0.12]), and low-dose atropine (refraction change: 0.53 [0.21–0.85]; axial length change: −0.15 [−0.25 to −0.05]) markedly slowed myopia progression. Pirenzepine (refraction change: 0.29 [0.05–0.52]; axial length change: −0.09 [−0.17 to −0.01]), orthokeratology (axial length change: −0.15 [−0.22 to −0.08]), and peripheral defocus modifying contact lenses (axial length change: −0.11 [−0.20 to −0.03]) showed moderate effects. Progressive addition spectacle lenses (refraction change: 0.14 [0.02–0.26]; axial length change: −0.04 [−0.09 to −0.01]) showed slight effects. Conclusions This network analysis indicates that a range of interventions can significantly reduce myopia progression when compared with single vision spectacle lenses or placebo. In terms of refraction, atropine, pirenzepine, and progressive addition spectacle lenses were effective. In terms of axial length, atropine, orthokeratology, peripheral defocus modifying contact lenses, pirenzepine, and progressive addition spectacle lenses were effective. The most effective interventions were pharmacologic, that is, muscarinic antagonists such as atropine and pirenzepine. Certain specially designed contact lenses, including orthokeratology and peripheral defocus modifying contact lenses, had moderate effects, whereas specially designed spectacle lenses showed minimal effect.

Purpose To determine the prevalence and risk factors of myopic maculopathy and specific optic disc and macular changes in highly myopic eyes of young Asian adults and their impact on visual acuity. Design Prospective cross-sectional study. Methods In total, 593 highly myopic (spherical equivalent refraction [SER] less than −6.00 diopters [D]) and 156 emmetropic (SER between −1.00 and +1.00 D) male participants from a population-based survey were included. All participants underwent standardized medical interviews, ophthalmic examination, and color fundus photographs. These photographs were graded systematically to determine the presence of optic disc and macular lesions. Myopic maculopathy was classified based on the International Classification of Myopic Maculopathy. Results The mean age was 21.1 ± 1.2 years. The mean SER for the highly myopic and emmetropic group was −8.87 ± 2.11 D and 0.40 ± 0.39 D, respectively ( P P Conclusions Our study showed that myopia-related changes of the optic disc and macula were common in highly myopic eyes even at a young age. The risk factors for myopic maculopathy include increased age, longer AL, and reduced choroidal thickness. Some of these changes were associated with reduced central visual function.

Trait theories of leadership have documented the role of individual characteristics in affecting leadership. Twin studies have further revealed significant genetic effects on leadership role occupancy. In the era of genomics, the current research examines how a dopamine transporter gene, DAT1, is involved in genetic influences on leadership role occupancy. Study 1 found DAT1 10-repeat allele to negatively relate to proactive personality, which in turn was positively associated with leadership role occupancy. The negative indirect effect was significant, but the overall relationship between this gene and leadership was not. In addition to replicating Study 1's findings using a nationally representative sample, Study 2 revealed another countervailing mechanism: DAT1 was positively related to (moderate) rule breaking, which was positively associated with leadership role occupancy. Consistent findings across the two studies suggest that the pathways linking specific genes to leadership are complex and a middle-ground approach is needed in such multidisciplinary investigations.

Background Maternal diet during pregnancy can influence fetal growth. However, the relation between maternal macronutrient intake and birth size outcomes is less clear. Objective We examined the associations between maternal macronutrient intake during pregnancy and infant birth size. Methods Pregnant women (n = 835) from the Singapore GUSTO (Growing Up in Singapore Towards healthy Outcomes) mother-offspring cohort were studied. At 26-28 wk of gestation, the macronutrient intake of women was ascertained with the use of 24 h dietary recalls and 3 d food diaries. Weight, length, and ponderal index of their offspring were measured at birth. Associations were assessed by substitution models with the use of multiple linear regressions. Results Mean ± SD maternal energy intake and percentage energy from protein, fat, and carbohydrates per day were 1903 ± 576 kcal, 15.6% ± 3.9%, 32.7% ± 7.5%, and 51.6% ± 8.7% respectively. With the use of adjusted models, no associations were observed for maternal macronutrient intake and birth weight. In male offspring, higher carbohydrate or fat intake with lower protein intake was associated with longer birth length (β = 0.08 cm per percentage increment in carbohydrate; 95% CI: 0.04, 0.13; β = 0.08 cm per percentage increment in fat; 95% CI: 0.02, 0.13) and lower ponderal index (β = -0.12 kg/m(3) per percentage increment in carbohydrate; 95% CI: -0.19, -0.05; β = -0.08 kg/m(3) per percentage increment in fat; 95% CI: -0.16, -0.003), but this was not observed in female offspring (P-interaction Conclusions Maternal macronutrient intake during pregnancy was not associated with infant birth weight. Lower maternal protein intake was significantly associated with longer birth length and lower ponderal index in male but not female offspring. However, this finding warrants further confirmation in independent studies. This trial was registered at clinicaltrials.gov as NCT01174875.

Objective To evaluate the association between refractive errors and age-related macular degeneration (AMD). Main Outcome Measures A clear understanding of the relationship between refractive error and AMD provides insights into the pathophysiology of AMD. Methods We searched PubMed and Embase from their inception to July 2012 for population-based studies with data on refractive error and AMD assessed from retinal photographs at baseline and follow-up. We performed separate meta-analyses for cross-sectional studies and cohort studies using adjusted odds ratios (ORs) and hazard ratios (HRs) under random effects models, respectively. Results Analysis of the 6 cross-sectional studies showed that hyperopia was associated with higher odds of prevalent AMD (pooled OR hyperopia vs. emmetropia: 1.16; 95% confidence interval [CI], 1.04–1.29) and that myopia was associated with lower odds of prevalent AMD (pooled OR myopia vs. emmetropia: 0.75; 95% CI, 0.61–0.92). Analysis from the 3 cohort studies showed nonsignificant associations. Analysis of the 5 cross-sectional and 2 cohort studies showed that each diopter increase in spherical equivalent was associated with increased odds of both prevalent (pooled OR, 1.09; 95% CI, 1.06–1.12) and incident (pooled HR, 1.06; 95% CI, 1.02–1.10) AMD. In 3 cross-sectional studies with data on axial length, each millimeter increase in axial length was associated with a decreased odd of prevalent AMD (pooled OR, 0.76; 95% CI, 0.69–0.85). Conclusions Refractive error is associated with AMD, although a temporal relationship cannot be determined on the basis of current evidence. Ophthalmologists should be aware that risk of AMD clinically seems to vary by refractive status. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Asymmetry of the neonatal brain is not yet understood at the level of structural connectivity. We utilized DTI deterministic tractography and structural network analysis based on graph theory to determine the pattern of structural connectivity asymmetry in 124 normal neonates. We tracted white matter axonal pathways characterizing interregional connections among brain regions and inferred asymmetry in left and right anatomical network properties. Our findings revealed that in neonates, small-world characteristics were exhibited, but did not differ between the two hemispheres, suggesting that neighboring brain regions connect tightly with each other, and that one region is only a few paths away from any other region within each hemisphere. Moreover, the neonatal brain showed greater structural efficiency in the left hemisphere than that in the right. In neonates, brain regions involved in motor, language, and memory functions play crucial roles in efficient communication in the left hemisphere, while brain regions involved in emotional processes play crucial roles in efficient communication in the right hemisphere. These findings suggest that even at birth, the topology of each cerebral hemisphere is organized in an efficient and compact manner that maps onto asymmetric functional specializations seen in adults, implying lateralized brain functions in infancy.

Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than −6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is highly heritable, and to date multiple gene loci have been reported. We performed exome sequencing in 4 individuals from an 11-member family of European descent from the United States. Affected individuals had a mean dioptric spherical equivalent of −22.00 sphere. A premature stop codon mutation c.157C>T (p.Gln53*) cosegregating with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent analyses identified three additional mutations in three highly myopic unrelated individuals (c.341G>A, c.418G>A, and c.776C>T). To determine differential gene expression in a developmental mouse model, we induced myopia by applying a −15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Copper deficiencies have been linked with photoreceptor loss and myopia with increased scleral wall elasticity. Retinal thinning has been reported with an SC02 variant. Human mutation identification with support from an induced myopic animal provides biological insights of myopic development.

PURPOSE: To determine the associations of myopia and axial length (AL) with major age-related eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), age-related cataract, and primary open-angle glaucoma (POAG). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 3400 Indians (75.6% response rate) aged 40 to 84 years in Singapore. METHODS: Refractive error was determined by subjective refraction, and AL was determined by noncontact partial coherence laser interferometry. Age-related macular degeneration and DR were defined from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System and Airlie House classification system, respectively. Age-related cataract was diagnosed clinically using the Lens Opacity Classification System (LOCS) III system. Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria. MAIN OUTCOME MEASURES: Age-related macular degeneration, DR, age-related cataract, and POAG. RESULTS: Myopic eyes (spherical equivalent [SE]

Purpose Myopia is a common complex condition influenced by genetic and environmental factors. Two recent genome-wide association studies have identified loci on chromosomes 15q25 and 15q14 associated with refractive error in Caucasian populations. Our study aimed to assess the association of these 2 loci with refractive error and ocular biometric measures in an independent ethnically matched Caucasian cohort. Design Genetic association study using unrelated individuals. Participants Blue Mountains Eye Study (BMES) cohort. A total of 1571 individuals were included in this study. Methods Single nucleotide polymorphism (SNP) genotype data were collected from the BMES cohort as part of the Wellcome Trust Case Control Consortium 2. Imputation was performed using MACH version 1.1.16, and statistical analysis was conducted using PLINK. Association tests were performed at both loci using refractive error (spherical equivalent), axial length, corneal curvature, and anterior chamber depth as the phenotypes. Main Outcome Measures Refractive error, axial length, corneal curvature, and anterior chamber depth. Results A total of 1571 individuals were available from the BMES for analysis. A statistically significant association for refractive error was evident for SNPs at the 15q14 locus, with P values ranging from 1.5×10 −2 at rs685352 to 6.4×10 −4 at rs560764, whereas association could not be confirmed for SNPs at the 15q25 locus, with P values ranging from 8.0×10 −1 to 6.4×10 −1 . Ocular biometric analysis revealed that axial length was the most likely trait underlying the refractive error association at the 15q14 locus for SNPs rs560766 ( P =0.0054), rs634990 ( P =0.0086), and rs8032019 ( P =0.0081). Conclusions Our results confirm the association with refractive error at the 15q14 locus but do not support the association observed at the 15q25 locus. Axial length seemed to be a major parameter at the 15q14 locus, underscoring the importance of this locus in myopia and future clinical treatment. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

This paper presents the growth pattern and sexual dimorphism of the thalamus and basal ganglia in a large-scale Asian neonatal cohort using both T2-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Our study observed a robust growth of the thalamus and basal ganglia (caudate, putamen, globus pallidus, and anterior limb of internal capsule) beyond the overall brain growth in the early postnatal period (36–43 weeks of the gestational age). Additionally, the microstructure of the two structures was integrated as reflected by an increase in fractional anisotropy (FA) and a decrease in axial and radial water diffusivities in the first few weeks of life. Sexual dimorphism was only observed in the whole brain growth and the left thalamic volume but not in the other volumes or DTI measures of the basal ganglia and thalamus at birth. Even though the pattern of sexual dimorphism in the total brain volume is present at birth and persists throughout postnatal brain development, sexual dimorphisms of the basal ganglia and thalamus differ from those found in later stages of brain development, indicating that regionally distinct patterns of postnatal brain development between males and females arise after birth.

Purpose To describe the prevalence of and risk factors for diabetic retinopathy (DR) in Indian persons living in a newly urbanized society in Asia. Design Population-based study. Participants Ethnic Indians aged ≥40 years living in Singapore. Methods The Singapore Indian Eye Study was conducted between 2007 and 2009. All participants underwent an extensive ophthalmic examination, including retinal photographs obtained after pupil dilation. These images were graded for the presence and severity of DR using the modified Airlie House classification system. Diabetes was defined as hemoglobin A1c level of ≥6.5%, use of diabetic medication, or a physician diagnosis of diabetes. Risk factors were measured using questionnaires, clinical assessments, or laboratory tests. Main Outcome Measures Any DR, diabetic macular edema (DME), or vision-threatening DR (VTDR). Results Among the 3400 participants, the age-standardized prevalence was 33.6% (95% confidence interval [CI], 31.4–35.8) for diabetes and 10.5% (95% CI, 9.3–11.8) for DR. Among those with diabetes only, the age-standardized prevalence was 30.4% (95% CI, 26.5–34.8) for any DR, 7.2% (95% CI, 5.3–9.7) for DME, and 7.1% (95% CI, 5.4–9.5) for VTDR. In multivariate analysis, independent risk factors for any DR were younger age (odds ratio [OR], 0.98; 95% CI, 0.96–1.00, per year increase), longer diabetes duration (OR, 1.09; 95% CI, 1.07–1.11 per year increase), higher hemoglobin A1c (OR, 1.23; 95% CI, 1.13–1.34 per percent increase), higher systolic blood pressure (OR, 1.01; 95% CI, 1.00–1.02 per 1-mmHg increase), lower diastolic blood pressure (OR, 0.97; 95% CI, 0.96–0.99 per 1-mmHg increase), history of previous stroke (OR, 2.16; 95% CI, 1.12–4.16), and insulin treatment (OR, 2.99; 95% CI, 1.84–4.87). Similar independent risk factors, except for blood pressure, were found for VTDR. Additionally, persons with lower income and living in smaller houses were associated with VTDR. Conclusions One in 3 migrant Indians living in newly urbanized Asian societies have diabetes and 1 in 10 has DR. This is similar to rates reported in Western populations and significantly higher than those reported in India. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Purpose To describe the prevalence and risk factors of pterygium in a multiethnic Asian population and to examine racial differences. Design Population-based study in Singapore, located 1° north of the equator. Participants Data were analyzed from 8906 participants from 3 population-based studies of Malays, Indians, and Chinese persons 40 years of age and older conducted between 2004 and 2011. Methods Standardized slit-lamp examinations were performed by trained study ophthalmologists to examine the anterior segment for evidence of pterygium. Every subject underwent standardized systemic and ocular examinations, interviewer-administered questionnaires, and blood investigations for risk factor assessment. Regression and principle component analysis models were constructed to study the relationship of race and other factors to pterygium. Main Outcome Measures Any pterygium and severe (grade 3 or opaque) pterygium. Results The overall prevalence of any pterygium was 10.1% (n = 900), of which severe pterygium was seen in 1.6% (n = 142). The prevalence of any pterygium was more common in Malays (15.5%) than Chinese (7.0%; P P P P P P P P P = 0.02), but race was not a significant risk factor in multivariate analysis. Conclusions This population-based study in Asian persons of different races living in the same geographical location at the equator indicated that race is a significant risk factor for pterygium, with Malays having higher prevalence than Indians and Chinese, while controlling for other risk factors. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Myopia has emerged as a major health issue in east Asia, because of its increasingly high prevalence in the past few decades (now 80-90% in school-leavers), and because of the sight-threatening pathologies associated with high myopia, which now affects 10-20% of those completing secondary schooling in this part of the world. Similar, but less marked, changes are occurring in other parts of the world. The higher prevalence of myopia in east Asian cities seems to be associated with increasing educational pressures, combined with life-style changes, which have reduced the time children spend outside. There are no reported major genes for school myopia, although there are several genes associated with high myopia. Any genetic contribution to ethnic differences may be small. However, to what extent many genes of small effect and gene-environment interactions contribute to variations in school myopia within populations remains to be established. There are promising optical and pharmacological interventions for preventing the development of myopia or slowing its progression, which require further validation, and promising vision-sparing treatments for pathological myopia.

Purpose To describe the prevalence and causes of visual impairment and blindness in an urban Indian population. Design Population-based study. Participants Ethnic Indians aged more than 40 years living in Singapore. Methods Participants underwent standardized ophthalmic assessments for visual impairment and blindness, defined using best-corrected visual acuity (BCVA) and presenting visual acuity (PVA), according to US and modified World Health Organization (WHO) definitions. Main Outcome Measures Unilateral visual impairment or blindness was defined on the basis of the worse eye, and bilateral visual impairment or blindness was defined on the basis of the better eye. Primary causes of visual impairment were determined. Results A total of 3400 eligible individuals (75.6% response rate) participated. On the basis of US definitions, the age-standardized prevalence was 0.4% for bilateral blindness (≤20/200, better eye) and 3.4% for bilateral visual impairment ( 20/200, better eye). Another 0.3% of bilateral blindness and 13.4% of bilateral visual impairment were correctable with refraction. Cataract was the principal cause of best-corrected bilateral blindness (60.0%) and bilateral visual impairment (65.7%). Other major causes of blindness and visual impairment included diabetic retinopathy, age-related macular degeneration, glaucoma, corneal opacity, and myopic maculopathy. Conclusions The prevalence of bilateral blindness and visual impairment in Indians living in Singapore is lower than estimates from populations living in India, but similar to estimates obtained from Singapore Malay and Chinese populations. Cataract is the leading cause of blindness and visual impairment. One in 20 cases of bilateral blindness and 1 in 10 cases of bilateral visual impairment are attributable to diabetic retinopathy. These data may have relevance to many ethnic Indian persons living outside India. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective Prior studies have reported that blood pressure (BP) has a significant influence on retinal vascular caliber both in adults and children aged 6 years and older. This study aimed to examine the association between BP and retinal vascular caliber in Singapore Chinese preschoolers 4 to 5 years of age. Design Population-based, cross-sectional study. Participants A total of 385 eligible and healthy Singapore Chinese children 4 to 5 years of age who were recruited in The Strabismus, Amblyopia and Refractive Error Study in Singaporean Chinese Preschoolers from May 2006 through October 2008 underwent BP measurements and retinal photography. Methods According to standard protocols, BP was measured with an automatic Omron sphygmomanometer (Omron HEM 705 LP, Omron Healthcare, Inc., Bannockburn, IL) and a retinal photograph was obtained with a Canon 45° digital retinal camera (Model CR6-NM45, Canon, Inc., Tokyo, Japan) after pupil dilation. Anthropometric and optical biometric measurements such as height, weight, and axial length were obtained also. Information regarding sociodemographic status and child birth information was supplied by parents in either English or Chinese questionnaires. Main Outcome Measures The computer imaging program was used to measure the caliber of all retinal arterioles and venules located in zone B. The central retinal arteriolar equivalent and central retinal venular equivalent were estimated by using a revised Knudtson-Parr-Hubbard formula. Results The mean retinal arteriolar and venular calibers were 156.19 μm and 220.01 μm in boys and 161.97 μm and 224.22 μm in girls. Higher systolic BP was associated with narrower retinal arterioles. After adjusting for age, gender, father's education, body mass index, birth weight, axial length, and caliber of the fellow retinal vessel, each 10-mmHg increase in systolic BP was associated with 2.00 μm (95% confidence interval, 0.39–3.61; P = 0.02) of retinal arteriolar narrowing and 2.51 μm (95% confidence interval, 0.35–4.68; P = 0.02) of retinal venular widening. However, neither diastolic BP nor mean arterial BP was associated with retinal arteriolar or venular caliber. Conclusions In very young children 4 to 5 years of age, higher systolic BP was associated with narrower retinal arterioles and wider retinal venules. This suggests that elevated BP may affect the retinal microvasculature from early childhood. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To examine the relationship between refractive error and optic disc topographic parameters and retinal nerve fiber layer (RNFL) thickness.Population-based cross-sectional study.All 3,280 (78.7% response rate) persons of Asian Malay ethnicity 40 to 80 years of age underwent a standardized interview, ocular examinations, and optic disc imaging with the Heidelberg Retina Tomography II (HRT; Heidelberg Engineering). Associations between spherical equivalent (SE) and HRT parameters were evaluated by partial correlation analysis.There were 2,457 (74.9%) right eyes with good-quality HRT images for analyses. When compared with emmetropic eyes, highly myopic eyes (SE-6.0 diopters) had greater disc area, rim area, rim volume, whereas hyperopic eyes (SE0.5 diopters) had significantly smaller disc area, rim area, and cross-sectional RNFL area (all P.005). In partial correlation after adjustment for age, sex, body mass index, intraocular pressure, and optic disc area, increase of SE (toward hyperopia) was related significantly with greater cup area (partial correlation coefficient, r = 0.058; P = .004) and cup-to-disc area ratio (r = 0.058; P = .004) and with smaller optic disc area (r = -0.058; P = .004), rim area (r = 0.058; P = .004), and rim volume (r = -0.091; P.001).This population-based study shows that refractive error is significantly (but weakly) associated with HRT parameters of disc area, cup area, rim area, cup-to-disc area ratio, and rim volume. The clinical significance of these associations need to be determined in further studies.

Objective To determine susceptibility genes for high myopia in Singaporean Chinese. Design A meta-analysis of 2 genome-wide association (GWA) datasets in Chinese and a follow-up replication cohort in Japanese. Participants and Controls Two independent datasets of Singaporean Chinese individuals aged 10 to 12 years (Singapore Cohort Study of the Risk factors for Myopia [SCORM]: cases=65, controls=238) and more than 21 years (Singapore Prospective Study Program [SP2]: cases=222, controls=435) for GWA studies, and a Japanese dataset aged more than 20 years (cases = 959, controls=2128) for replication. Methods Genomic DNA samples from SCORM and SP2 were genotyped using various Illumina Beadarray platforms (>HumanHap 500). Single-locus association tests were conducted for each dataset with meta-analysis using pooled z-scores. The top-ranked genetic markers were examined for replication in the Japanese dataset. Fisher P was calculated for the combined analysis of all 3 cohorts. Main Outcome Measures High myopia, defined by spherical equivalent (SE)≤−6.00 diopters (D); controls defined by SE between −0.50 and +1.00 D. Results Two SNPs (rs12716080 and rs6885224) in the gene CTNND2 on chromosome 5p15 ranked top in the meta-analysis of our Chinese datasets (meta P = 1.14×10 −5 and meta P = 1.51×10 −5 , respectively) with strong supporting evidence in each individual dataset analysis (max P = 1.85×10 −4 in SCORM: max P = 8.8×10 −3 in SP2). Evidence of replication was observed in the Japanese dataset for rs6885224 ( P = 0.035, meta P of 3 datasets: 7.84×10 −6 ). Conclusions This study identified a strong association of CTNND2 for high myopia in Asian datasets. The CTNND2 gene maps to a known high myopia linkage region on chromosome 5p15. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

To assess the influence of the spectrum of diabetic retinopathy (DR) on vision-specific function in an Asian population.Population-based cross-sectional study.Persons aged 40 to 80 years of Malay ethnicity in Singapore.The Singapore Malay Eye Study was a population-based, cross-sectional study of 3280 Asian Malays (78.7% response rate). Five end points were considered: (1) any DR, (2) macular edema (ME), (3) clinically significant macular edema (CSME), (4) vision-threatening DR (VTDR), and (5) DR severity levels ranging from none to proliferative diabetic retinopathy (PDR). Vision function was assessed using the Vision-Specific Functioning Scale validated using Rasch analysis.Vision-specific functioning score.Of 357 diabetic participants in the study, 23.2% had any DR, 5.6% had ME, 5.0% had CSME, 10.6% had VTDR, and 6.2% had PDR. In linear regression models adjusting for age, gender, stroke, diabetic risk factors, and socioeconomic factors, poorer vision-specific function was associated independently with any DR (beta, -0.21; P0.05), ME (beta, -0.48; P0.05), CSME (beta, -0.42; P0.05), VTDR (beta, -0.64; P0.05), and PDR (beta, -0.92; P0.001). When controlling further for presenting visual acuity, VTDR (beta, -0.37; P = 0.01) and PDR (beta, -0.61; P = 0.002) were the only 2 DR categories independently associated with poorer vision-specific function and PDR. Persons with VTDR and PDR were 6 to 12 times more likely to report lower participation in daily living activities than those without these DR levels.People with VTDR and PDR have substantial difficulty undertaking vision-specific daily activities. These findings reinforce the importance of preventative efforts targeted at the earliest DR stages to prevent progression to later stages of DR.Proprietary or commercial disclosure may be found after the references.

Purpose Eyes with myopia may be less likely to develop diabetic retinopathy (DR). The relationship between refractive error, ocular biometry, and DR therefore was investigated. Design Population-based, cross-sectional study. Participants Persons with diabetes from the Singapore Malay Eye Study (SiMES). Methods Diabetes mellitus was defined as random glucose of 11.1 mmol/l or more, use of diabetic medication, or a physician diagnosis of diabetes. Spherical equivalent refraction (SE) was assessed using an autokeratorefractometer and subjective refraction. Axial length (AL) and anterior chamber depth (ACD) were measured by IOLMaster (Carl Zeiss Meditec AG, Jena, Germany). Diabetic retinopathy was graded from retinal photographs. Main Outcome Measures Any DR was defined by characteristic lesions defined by the Early Treatment Diabetic Retinopathy Study (ETDRS); moderate DR by ETDRS retinopathy severity scores of 43 or higher; and vision-threatening retinopathy by severe nonproliferative retinopathy, proliferative DR, or clinically significant macular edema. Results Of 3280 adult Malay participants (78.7% response), 629 persons with diabetes contributed to this analysis. In multivariate analyses adjusting for age, gender, education, height, cataract, hypertension, hemoglobin A1c, and other factors, eyes with myopic SE were less likely to have any DR (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.84–0.96; P = 0.002, per 1-diopter [D] decrease), moderate DR (OR, 0.83; 95% CI, 0.73–0.93; P = 0.001, per 1-D decrease), and vision-threatening DR (OR, 0.77; 95% CI, 0.67–0.88; P P = 0.041, per 1-mm increase), moderate DR (OR, 0.80; 95% CI, 0.62–1.05; P = 0.11, per 1-mm increase), and vision-threatening DR (OR, 0.63; 95% CI, 0.40–0.99; P = 0.044, per mm increase). Eyes with deeper ACD were less likely to have moderate DR (OR, 0.32; 95% CI, 0.16–0.64; P = 0.001, per 1-mm increase) and vision-threatening DR (OR, 0.14; 95% CI, 0.06–0.36; P = 0.001, per 1-mm increase). Conclusions Myopic refraction and longer AL are associated with a lower risk of DR, particularly vision-threatening retinopathy, without any evidence of a threshold. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective To evaluate the performance of the Heidelberg Retina Tomograph II (HRT II, Heidelberg Engineering, Heidelberg, Germany) in diagnosing glaucoma in a population setting. Design Population-based cross-sectional study. Participants Of 3280 Malay persons aged 40 to 80 years who participated in the survey, 112 subjects (124 eyes) with glaucoma and a subset of 196 bilaterally normal subjects (392 eyes) were included for the evaluation of diagnostic ability of HRT II. Methods All glaucomatous and normal eyes underwent standardized ophthalmic assessment (including automated perimetry) and HRT II. Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria. Area under the curve (AUC) receiver operating characteristic (ROC), sensitivity, and specificity were used to evaluate the diagnostic performance of HRT II algorithms. Marginal logistic regression models were used to evaluate the influence of optic disc size on the results of HRT II algorithms. Main Outcome Measures The HRT II algorithms: linear discriminant functions (LDFs) by Mikelberg et al (LDF1), Burk et al (LDF2), Bathija et al (LDF3), and Moorfields regression analysis (MRA). The MRA was subdivided into MRA1 with "borderline" outcomes as positive and MRA2 with "borderline" outcomes as negative. Results Subjects with cataract, visual impairment, astigmatism, and greater negative spherical equivalent, and of older age were more likely to yield lower quality images. For analyses by eye, AUCs were 0.789, 0.704, 0.755, 0.754, and 0.762 for MRA1, MRA2, LDF1, LDF2, and LDF3, respectively. At 85% specificity, sensitivities were 62.1%, 65.3%, and 66.9% for LDF1, LDF2, and LDF3, respectively. At 95% specificity, these figures decreased to 31.5%, 42.7%, and 45.2%, respectively. The sensitivity and specificity were 71.0% and 86.7% for MRA1 and 43.6% and 97.2% for MRA2, respectively. Similar estimates were found for analyses by person. Larger optic disc size was associated with increased sensitivity and false-positive rate for MRA1, LDF1, and LDF2. LDF1 and LDF3 were least affected by optic disc area, but the sensitivities were moderate and the false-positive rates were high across different optic disc areas. Conclusions The current HRT II algorithms are of limited value for population-based glaucoma screening in the Malay population and do not account adequately for optic disc size. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose To describe the prevalence and risk factors of diabetic retinopathy in Asian Malays. Design Population-based cross-sectional study. Participants Persons with diabetes of Malay ethnicity aged 40 to 80 years in Singapore. Methods Diabetes mellitus was defined as random glucose of 11.1 mmol/l or more, use of diabetic medication, or a physician diagnosis of diabetes. Retinal photographs taken from both eyes were graded for diabetic retinopathy using the modified Airlie House classification system. Main Outcome Measures Any diabetic retinopathy, retinopathy grades, macular edema, or vision-threatening retinopathy. Results Of the 3261 persons who participated in this study, 757 (23.1%) had diabetes and gradable retinal photographs. In persons with diabetes, the overall prevalence of any retinopathy was 35.0% (95% confidence interval [CI], 28.2–43.4), the overall prevalence of macular edema was 5.7% (95% CI, 3.2–9.9), and the overall prevalence of vision-threatening retinopathy was 9.0% (95% CI, 5.8–13.8). Compared with men, women had significantly higher proportions with more severe diabetic retinopathy, moderate (12% vs. 4%) and severe (3% vs. 0.2%) nonproliferative retinopathy, proliferative retinopathy (7% vs. 2%), and vision-threatening retinopathy (13% vs. 3%). In multiple logistic regression, independent risk factors for any retinopathy were longer diabetes duration (odds ratio [OR], 1.07; 95% CI, 1.04–1.09, per year increase), higher hemoglobin A1 c (OR, 1.21; 95% CI, 1.10–1.33, per % increase), hypertension (OR, 1.85; 95% CI, 1.04–3.30), and higher pulse pressure (OR, 1.34, 95% CI, 1.19–1.51, per 10-mmHg increase); older age (OR, 0.73; 95% CI, 0.57–0.93, per decade increase) and higher total cholesterol levels (OR, 0.75; 95% CI, 0.63–0.89, per 1-mmol/l increase) were protective of any retinopathy. Vision-threatening retinopathy additionally was associated with previous stroke (OR, 3.74; 95% CI, 1.24–11.26), cardiovascular disease (OR, 2.23; 95% CI, 1.08–4.62), and chronic kidney disease (OR, 4.45; 95% CI, 2.18–9.07). Female gender was not an independent risk factor for diabetic retinopathy after adjusting for metabolic and socioeconomic risk factors. Conclusions One in 10 Malay adults with diabetes in Singapore has vision-threatening diabetic retinopathy. Risk factors for retinopathy in this population are largely similar to white populations elsewhere, suggesting that control of these risk factors may reduce both the prevalence and impact of retinopathy. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

Objective To describe the prevalence of age-related macular degeneration (AMD) in an Asian Malay population. Design Population-based cross-sectional study. Participants An age-stratified random sample of Malay persons aged 40 to 80 years living in Singapore. Methods Participants were invited to a central clinic for a comprehensive examination. Main Outcome Measures Early and late AMD signs were graded from retinal photographs following the Wisconsin grading system. Results Of 3280 participants who participated (78.7% response rate), 3265 had photographs of sufficient quality for grading of AMD signs. Early and late AMD were present in 160 (4.9%) and 23 (0.70%) participants, respectively. After age standardization, the prevalence of early AMD in Malay persons aged 40 to 80 years was estimated to be 3.5% (95% confidence interval [CI], 2.9%–4.1%) and that of late AMD was 0.34% (95% CI, 0.20%–0.49%). Early AMD was more prevalent in men than in women (6.1% vs. 3.8%); this was significant despite adjusting for age and smoking (odds ratio [OR], 1.56; 95% CI, 1.11–2.20). Late AMD also was more prevalent in men than in women (1.0% vs. 0.4%), although this was not statistically significant after adjusting for age and smoking (OR, 1.39; 95% CI, 0.52–3.68). The prevalence of early and late AMD was similar to that reported in the Blue Mountains Eye Study among white persons. Conclusions The prevalence of AMD in Asian Malay people is similar to that in white persons from the Blue Mountains Eye Study. Early AMD signs were more frequent in men compared with women, an association that was not fully explained by the higher smoking rates in men. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

Purpose To examine the prevalence and risk factors of retinal arteriolar emboli, a risk predictor of stroke, in an Asian population. Design Population-based cross-sectional study. Methods Retinal emboli were ascertained from retinal photographs obtained from both eyes of 3,265 Asian Malays, aged 40 to 80 years, according to a standardized protocol. Risk factors were assessed from detailed standardized interviews, clinical examinations, and laboratory investigations. Results The overall prevalence of retinal emboli was 0.6% (95% confidence interval [CI], 0.58 to 0.62). A finding of retinal emboli was strongly associated with increasing age (P = .005, for trend), but age-stratified prevalence rates were still lower than those reported from previous population-based studies of White persons. After adjusting for age and gender, the presence of retinal emboli was associated with cigarette smoking (odds ratio [OR], 5.96; 95% CI, 1.75 to 20.32), elevated total cholesterol (OR, 5.21; 95% CI, 1.93 to 12.82), low-density lipoprotein cholesterol (OR, 2.98; 95% CI, 1.20 to 7.39), and self-reported history of angina (OR, 5.67; 95% CI, 1.62 to 19.91). These associations remained significant in multivariate analysis with additional adjustment for other risk factors. Conclusions Retinal emboli are less common in Asians than in similarly aged White persons, but are associated with similar cardiovascular risk factors.

Purpose To describe the prevalence and risk factors for myopia and other refractive errors in an urban Malay population in Singapore. Design Population-based, cross-sectional study. Participants Persons of Malay ethnicity, between 40 and 80 years of age, living in Singapore. Methods Refractive error was determined by subjective refraction and if unavailable by autorefraction. Data were analyzed for 2974 adults without previous cataract surgery and who had right eye refraction data. Risk factor data, such as education levels and near work activity, were obtained from a face-to-face interview. Main Outcome Measures Myopia, defined as spherical equivalent (SE) refraction less than −0.5 diopters (D), astigmatism as cylinder less than −0.5 D, hyperopia as SE greater than 0.5 D, and anisometropia as the difference in SE greater than 1.0 D. Results The prevalence of myopia in the right eye was 30.7% (9.4% unilateral myopia and 21.3% bilateral myopia), the prevalence of astigmatism in the right eye was 33.3% (95% confidence interval [CI, 33.0–33.5), the prevalence of hyperopia in the right eye was 27.4% (95% CI, 24.7–27.6), and the prevalence of anisometropia was 9.9% (95% CI, 9.7–10.0). There was a U-shaped relationship between increasing age and the prevalence of myopia, which was partially explained by the age-related increase in the prevalence of cataract. In a multiple logistic regression model, female sex, age, higher educational level, and cataract were associated with myopia. Adults with myopia were more likely to have astigmatism ( P Conclusions A quarter of older adult Malay people in Singapore had myopia. Compared with previous reports of similarly aged Singapore Chinese adults, the prevalence of myopia, astigmatism, and anisometropia was lower, whereas the prevalence of hyperopia was similar. Financial Disclosure(s) The authors have no proprietary interest in any materials discussed in this article.

Objective To examine the relationship between visual acuity and mortality in a Chinese population. Design Population-based cohort study. Participants Chinese persons in Singapore ages 40 to 79 years at baseline examination. Methods The Tanjong Pagar Study in Singapore examined 1232 persons (response rate, 71.8%) at the baseline examination in 1997 and 1998. Participants had measurements of presenting and best-corrected visual acuity (VA) using standardized protocols. Mortality data were obtained from the National Death Registry, which linked subjects who had died since the baseline examination. Cause of death was determined from the International Classification of Diseases 9 codes. Analysis was performed on 1225 (99.4%) participants with VA data. Main Outcome Measure All-cause mortality. Results By December 31, 2004 (median follow-up, 6.8 years), 126 persons had died. Participants with presenting VA in the better eye worse than 20/40 (logarithm of the minimum angle of resolution [logMAR] score, 0.3) had a significantly higher mortality rate (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.4–6.3, adjusting for age, gender, hypertension, diabetes, smoking, heart attack, stroke, and income) as compared with participants with VA of 20/20 (logMAR, 0.0). Associations were similar for best-corrected VA in the better eye (HR, 2.7; 95% CI, 1.4–5.5). Among clinic participants with logMAR VA measurements, each 1-line difference in presenting VA (logMAR gain, 0.10) was associated with a 4-fold increased risk of mortality (HR, 4.4; 95% CI, 1.9–10.2). Conclusions In this Chinese population in Singapore, visual impairment was associated independently with an increased risk of mortality.

Topic To assess the evidence for the effectiveness of interventions to improve visual acuity (VA) and prevent or treat neovascularization secondary to central retinal vein occlusion (CRVO). Clinical Relevance Central retinal vein occlusion is a common cause of visual morbidity and blindness. Many different interventions have been advocated, but the evidence justifying their use remains unclear. Methods/Literature Reviewed English and non-English language articles were retrieved using a keyword search of Medline (1966 onwards), Embase, the Cochrane Collaboration, the National Institutes of Health Clinical Trials database, and the Association for Research in Vision and Ophthalmology (2003–2005). This was supplemented by manually searching references of review articles. Two investigators independently identified all randomized clinical trials (RCTs) on interventions in CRVO with more than 3 months’ follow-up. Results Of 4133 citations retrieved, 17 RCTs comparing intervention with a control group were identified. There were 4 RCTs on laser photocoagulation. Grid macular laser photocoagulation did not improve VA in CRVO with macular edema. Prophylactic panretinal photocoagulation did not prevent angle and iris neovascularization in ischemic CRVO, but resulted in regression of angle and iris neovascularization and reduced progression to neovascular glaucoma. There were 4 RCTs that reported improvement in VA with inpatient hemodilution, 2 RCTs with no significant improvement, and 1 RCT showing deterioration in VA after outpatient hemodilution. Randomized clinical trials evaluating ticlodipine, troxerutin, and streptokinase showed a limited or no benefit. Conclusions This review found limited level I evidence for any intervention to improve VA in patients with CRVO. Panretinal photocoagulation resulted in regression of neovascularization. Hemodilution may improve vision in some patients, but the data conflict. More robust randomized controlled trials evaluating current treatments for CRVO are needed. The results of ongoing RCTs on intravitreal triamcinolone, anti–vascular endothelial growth factor agents, and chorioretinal anastomosis are awaited with interest.

Objective To study the prevalence of undercorrected refractive error and associated sociodemographic factors among Singaporean Chinese adults. Design Cross-sectional, population-based survey. Participants Singaporean Chinese adults aged 40 to 79 years (n = 1152). Methods The Singapore electoral register of Tanjong Pagar was used as a sampling frame, and disproportionate, stratified, clustered, random sampling was performed. There were 1717 eligible adults and 1232 (71.8%) participated. Analysis was performed among 1152 adults with complete habitual and best-corrected visual acuity data. Main outcome measure Undercorrected refractive error was defined as improvement of better eye visual acuity of at least 2 lines or more with best possible refractive correction. Results The age- and gender-adjusted rate of undercorrected refractive error standardized directly by age and gender was 17.3% (95% confidence interval, 15.0, 19.5). Undercorrected refractive error rates were more common in older adults who had completed fewer years of education and in those who had cataract. People who did not wear spectacles tended to have poorer vision. Conclusions The undercorrected refractive error rate among Singaporean Chinese is relatively common compared with data from other populations.

Objective To determine the prevalence rates and causes of low vision, blindness, and patient-assessed deficient visual function among Singaporean Chinese adults. Design Population-based cross-sectional survey. Participants Singaporean Chinese adults 40 to 79 years old (n = 1152). Methods From an initial sampling frame of 40- to 79-year-old Chinese in the Tanjong Pagar district in Singapore, 2000 subjects were selected using a disproportionate, stratified, clustered, random-sampling method. Of 1717 eligible subjects, 1232 were examined (participation rate=71.8%), and 80 adults who did not have visual acuity (VA) data were excluded from the analysis. Main outcome measures Bilateral low vision was defined as best-corrected VA (BCVA) worse than 6/18 and 3/60 or better, and bilateral blindness as BCVA worse than 3/60 in the better eye or constriction of the visual field to within 10° of fixation, in accordance with the World Health Organization criteria. Patient-assessed visual function was measured using a modified VF-14 questionnaire. Results The age- and gender-adjusted prevalence rates were 1.1% (95% confidence interval [CI], 0.6–1.8) for bilateral low vision and 0.5% (95% CI, 0.2–1.1) for bilateral blindness, and the mean visual function score was 98.6. The rates of bilateral low vision and blindness increased with age, whereas visual function scores decreased with age, even after adjusting for gender and education. Cataract accounted for 58.8% of bilateral low vision, 20.0% of bilateral blindness, and 52.0% of poor visual function (score Conclusion The age- and gender-adjusted rates of low vision and blindness were 1.1% and 0.5%, respectively. Glaucoma is a leading cause of blindness in Singaporean Chinese adults, in addition to well-recognized causes in the rest of Asia such as cataract.

Purpose: To assess the interventions to treat acute angle closure (AAC) and primary angle closure (PAC) with or without glaucomatous optic neuropathy.Clinical Relevance: Primary angle closure is one of the leading causes of blindness in East Asia. At present, there are few clinical guidelines on the optimal treatment of AAC or PAC in the affected or contralateral eye.Methods: All randomized clinical trials, prospective controlled clinical trials, nonprospective controlled clinical trials, and retrospective case series with >50 cases that evaluated treatments for AAC or PAC were included. Studies published in the English language were identified from MEDLINE, PubMed, EMBASE, and the Cochrane Collaborations, as well as by a hand search of the reference lists of important articles.Results: Nine randomized clinical trials and 24 nonrandomized clinical trials and large case series were evaluated. Laser peripheral iridotomy (LPI) has been found to be as effective as surgical peripheral iridectomy in randomized clinical trials-of the affected and contralateral eyes of AAC or PAC patients with or without evidence of glaucoma. In another randomized clinical trial, latanoprost was found to decrease intraocular pressure (IOP) more than timolol for PAC in patients for whom LPI alone failed.Conclusions: This review suggests that LPI should be recommended for the treatment of affected and contralateral eyes of AAC patients. In patients with PAC and insufficient treatment with LPI, latanoprost eye drops may decrease IOP more than timolol. There is still insufficient evidence about other interventions for the treatment of AAC and PAC. (C) 2003 by the American Academy of Ophthalmology.

Objective To examine the risk factors for variations in ocular biometry parameters in Singapore Chinese children, a population with a known high prevalence rate of myopia at an early age. Design Cross-sectional study. Participants Children aged 7 to 9 years (n = 1453) from three schools in Singapore. Methods The children underwent A scan biometry and cycloplegic autorefraction measurements. Questions were asked regarding number of books read per week, night lighting, and parental myopia. Main outcome measures Axial length, vitreous chamber depth, lens thickness, anterior chamber depth, refraction, and corneal curvature radius measurements were made. Results After controlling for several factors, the axial lengths were found to be longer and vitreous chambers deeper in children who were older, male, read more than two books per week, or taller, and those who had at least one parent who was myopic. In these models, children who read more than two books per week had axial lengths that were 0.17 mm longer and vitreous chambers that were 0.15 mm deeper compared with children who read two or fewer books per week. Anterior chambers were deeper in males and taller children, whereas corneal curvature was steeper in female, older, and shorter children. Conclusions Increases of axial length and vitreous cavity depth were associated with older age, being male, reading more than two books per week, increased height, and parental history of myopia. Of these risk factors, however, neither reading nor parental myopia history were associated with values for anterior chamber depth, corneal curvature, or lens thickness. These findings confirm that conventional risk factors for myopia associated with the vitreous cavity, but suggest that anterior segment parameters such as corneal curvature and lens thickness may be subject to unrelated postnatal growth control mechanisms.

Topic To evaluate the efficacy of interventions such as eyedrops, bifocal lenses, or contact lenses in retarding the progression of myopia in myopic children. Clinical relevance Myopia is a common ocular disorder, and high myopia (myopia at least −6.0 diopters) is associated with potentially blinding conditions. At present, there are no general guidelines on interventions that may decrease myopia progression in children, but some interventions such as contact lenses are offered on an ad hoc basis. Methods or literature reviewed English and non-English language articles published from 1968 to 2000 were retrieved using a keyword search of MEDLINE, Embase, Cochrane Library, and Science Citation Index databases. Randomized controlled trials with comparisons of the effectiveness of interventions to decrease myopia progression in myopic children were reviewed. Results Ten clinical trials of different interventions to retard myopia progression were reviewed, including three trials that evaluated atropine and one trial that evaluated soft contact lenses. Atropine eye drops of 0.5% concentration were effective in clinical trials, but no significant effect was found for tropicamide or timolol eyedrops. Five of the six trials on bifocal spectacle lenses with various additions failed to show significant retardation, and results of the remaining trial were barely significant ( P = 0.047). A trial of soft contact lenses failed to show significant effects. Conclusions The latest evidence from randomized clinical trials does not provide sufficient information to support interventions to prevent the progression of myopia. Long-term large-scale double-masked randomized clinical trials, including cycloplegic refraction, are needed before any recommendations about interventions in clinical practice to prevent high myopia in myopic children are considered.