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Find video protocols related to scientific articles indexed in Pubmed.
Development and Reliability of Retinal Arteriolar Central Light Reflex Quantification System: A New Approach for Severity Grading.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 11-01-2014
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Purpose: To describe the methodology and assess the reliability and validity of a novel computer based semi-automated software which quantifies retinal arteriolar central light reflex (CR), a hypertensive retinopathy sign, from digital retinal photographs. Methods: Digital retinal photographs from the Singapore Malay Eye Study (SiMES), a population-based cross-sectional study of 3,280 (78.7% response) persons aged 40 to 80 years, were selected. Computer-assisted software was developed to quantify retinal arteriolar central light reflex (CR) by selecting vessel edge points semi-automatically. This software then automatically computes the CR, vessel diameter, and the CR to the vessel diameter ratio (CRR). 150 randomly selected retinal photographs from SiMES participants were used for the final analysis. Reliability parameters were assessed using intra-class correlation coefficient (ICC) and Bland-Altman Plots. The criterion validity of the new method was determined by examining the association between CRR and systemic and ocular factors. Results: The ICCs for the inter-grader and intra-grader CRR measurement were 0.76 (95% confidence interval [CI]: 0.53 - 0.89) and 0.86 (95% CI: 0.67 - 0.94), respectively. The ICC for intra-visit repeatability was 0.87 (95% CI: 0.71 - 0.95). In the multivariate model, a higher CRR was independently associated with elevated mean arterial blood pressure (per 10 mmHg increase) (?=0.017, p<0.001). Conclusions: We demonstrated that quantitative assessment of retinal arteriolar wall opacification is a reliable and valid method using a new computer-assisted system. Our new CRR measurement system can provide a useful tool to study retinal arteriolar abnormalities with systemic diseases potentially.
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Retinal microvasculature in Alzheimer's disease.
J. Alzheimers Dis.
PUBLISHED: 10-30-2014
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Although cerebral small vessel disease has been implicated in the development of Alzheimer's disease (AD), the cerebral microcirculation is difficult to visualize directly in vivo. As the retina and the brain share similar embryological origin, anatomical features and physiological properties with the cerebral small vessels, the retinal vessels thus offer a unique and easily accessible "window" to study the correlates and consequences of cerebral small vessel diseases in vivo. Retinal microvasculature can now be visualized, quantified and monitored non-invasively using state-of-the-art retinal imaging technology. Recent clinic- and population-based studies have demonstrated a link between retinal vascular changes and dementia, in particular AD, and cerebral small vessel disease. In this review, we summarize the current findings on retinal vascular changes such as retinopathy signs and changes in novel retinal vascular network parameters and retinal vascular caliber with dementia, cognitive dysfunction and cerebral small vessel disease, and discuss possible future research to further evaluate whether retinal vascular imaging might help to elucidate vascular mechanisms contributing to the development of AD and provide additional value in predicting who may be at risk of developing AD.
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Optic cup segmentation for glaucoma detection using low-rank superpixel representation.
Med Image Comput Comput Assist Interv
PUBLISHED: 10-22-2014
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We present an unsupervised approach to segment optic cups in fundus images for glaucoma detection without using any additional training images. Our approach follows the superpixel framework and domain prior recently proposed in, where the superpixel classification task is formulated as a low-rank representation (LRR) problem with an efficient closed-form solution. Moreover, we also develop an adaptive strategy for automatically choosing the only parameter in LRR and obtaining the final result for each image. Evaluated on the popular ORIGA dataset, the results show that our approach achieves better performance compared with existing techniques.
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Reliability and determinants of retinal vessel oximetry measurements in healthy eyes.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-11-2014
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To assess the reliability and determinants of retinal vessel oximetry measurements with the Oxymap T1 Retinal Oximeter in normal Asian eyes.
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cnvCapSeq: detecting copy number variation in long-range targeted resequencing data.
Nucleic Acids Res.
PUBLISHED: 09-16-2014
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Targeted resequencing technologies have allowed for efficient and cost-effective detection of genomic variants in specific regions of interest. Although capture sequencing has been primarily used for investigating single nucleotide variants and indels, it has the potential to elucidate a broader spectrum of genetic variation, including copy number variants (CNVs). Various methods exist for detecting CNV in whole-genome and exome sequencing datasets. However, no algorithms have been specifically designed for contiguous target sequencing, despite its increasing importance in clinical and research applications. We have developed cnvCapSeq, a novel method for accurate and sensitive CNV discovery and genotyping in long-range targeted resequencing. cnvCapSeq was benchmarked using a simulated contiguous capture sequencing dataset comprising 21 genomic loci of various lengths. cnvCapSeq was shown to outperform the best existing exome CNV method by a wide margin both in terms of sensitivity (92.0 versus 48.3%) and specificity (99.8 versus 70.5%). We also applied cnvCapSeq to a real capture sequencing cohort comprising a contiguous 358 kb region that contains the Complement Factor H gene cluster. In this dataset, cnvCapSeq identified 41 samples with CNV, including two with duplications, with a genotyping accuracy of 99%, as ascertained by quantitative real-time PCR.
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A survey on computer aided diagnosis for ocular diseases.
BMC Med Inform Decis Mak
PUBLISHED: 08-31-2014
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Computer Aided Diagnosis (CAD), which can automate the detection process for ocular diseases, has attracted extensive attention from clinicians and researchers alike. It not only alleviates the burden on the clinicians by providing objective opinion with valuable insights, but also offers early detection and easy access for patients.
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Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma.
Nat. Genet.
PUBLISHED: 08-31-2014
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We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. We observed genome-wide significant association at multiple SNPs near ABCA1 at 9q31.1 (rs2487032; P = 1.66 × 10(-8)) and suggestive evidence of association in PMM2 at 16p13.2 (rs3785176; P = 3.18 × 10(-6)). We replicated these findings in a set of 525 HPG cases and 912 controls from Singapore and a further set of 1,374 POAG cases and 4,053 controls from China. We observed genome-wide significant association with more than one SNP at the two loci (P = 2.79 × 10(-19) for rs2487032 representing ABCA1 and P = 5.77 × 10(-10) for rs3785176 representing PMM2). Both ABCA1 and PMM2 are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.
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Hemoglobin is associated with retinal vascular fractals in type 1 diabetes patients.
Ophthalmic Epidemiol
PUBLISHED: 08-18-2014
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Retinal vascular fractal dimension, a measure of the density of the retinal vasculature, has been suggested as a marker of systemic microvascular disorders in diabetes. As hemoglobin concentration is tightly related to vascular physiology and hypoxia, the hypothesis was that hemoglobin concentration would be associated with retinal vascular fractals in a relevant population.
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Dynamic responses in retinal vessel caliber with flicker light stimulation in eyes with diabetic retinopathy.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 07-17-2014
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This study investigated the responses of retinal vessels to flickering light in diabetic patients with various stages of diabetic retinopathy (DR).
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Accounting for standard errors of vision-specific latent trait in regression models.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 07-13-2014
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To demonstrate the effectiveness of Hierarchical Bayesian (HB) approach in a modeling framework for association effects that accounts for SEs of vision-specific latent traits assessed using Rasch analysis.
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Early signs of exudative age-related macular degeneration in Asians.
Optom Vis Sci
PUBLISHED: 07-01-2014
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To investigate the relationship between the early signs of age-related macular degeneration (AMD) and the risk of developing exudative AMD (typical AMD or polypoidal choroidal vasculopathy [PCV]) in the fellow eye of Japanese patients with unilateral exudative AMD, focusing particularly on eyes with only pigmentary abnormality.
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The Relationship between Changes in Body Mass Index and Retinal Vascular Caliber in Children.
J. Pediatr.
PUBLISHED: 06-30-2014
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To examine the longitudinal relationship between changes in childhood body mass index (BMI) and retinal vascular caliber.
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Ethnic variation in early age-related macular degeneration lesions between white Australians and Singaporean Asians.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 06-28-2014
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We compared early age-related macular degeneration (AMD) lesion characteristics between white Australians and Singaporean Asians.
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Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract.
Hum. Mol. Genet.
PUBLISHED: 06-20-2014
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Age-related cataract is a leading cause of blindness worldwide, especially in developing countries where access to cataract surgery remains limited. Previous linkage and candidate gene studies suggested genetic influences on age-related nuclear cataract but few genetic markers have been identified thus far. We conducted genome-wide association studies on 4569 Asians (including 2369 Malays and 2200 Indians), and replicated our analysis in 2481 Chinese from two independent cohorts (1768 Chinese in Singapore and 803 Chinese in Beijing). We confirmed two genome-wide significant loci for nuclear cataract in the combined meta-analysis of four cohorts (n = 7140). The first locus was at chromosome 3q25.31 in KCNAB1 (rs7615568, fixed-effect Pmeta = 2.30 × 10(-8); random-effect Pmeta = 1.08 × 10(-8)). The second locus was at chromosome 21 in the proximity of CRYAA (rs11911275, fixed-effect Pmeta = 2.77 × 10(-8); random-effect Pmeta = 1.98 × 10(-9)), a major protein component of eye lens. The findings were further supported by up-regulation and down-regulation of KCNAB1 and CRYAA in human lens capsule, respectively, as the severity of nuclear cataract increases. The results offer additional insights into the pathogenesis of nuclear cataract in Asians.
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Retinal vascular caliber and age-related macular degeneration in an Indian population from Singapore.
Ophthalmic Epidemiol
PUBLISHED: 06-19-2014
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To examine the association between retinal vascular caliber and early age-related macular degeneration (AMD) in an Indian population.
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Trends in age-related macular degeneration management in Singapore.
Optom Vis Sci
PUBLISHED: 06-01-2014
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To describe the trends and patterns of anti-vascular endothelial growth factor (anti-VEGF) therapy and photodynamic therapy (PDT) use for age-related macular degeneration (AMD) in the National Eye Centre in Singapore over a 4-year period.
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Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
Wanqing Wen, Wei Zheng, Yukinori Okada, Fumihiko Takeuchi, Yasuharu Tabara, Joo-Yeon Hwang, Rajkumar Dorajoo, Huaixing Li, Fuu-Jen Tsai, Xiaobo Yang, Jiang He, Ying Wu, Meian He, Yi Zhang, Jun Liang, Xiuqing Guo, Wayne Huey-Herng Sheu, Ryan Delahanty, Xingyi Guo, Michiaki Kubo, Ken Yamamoto, Takayoshi Ohkubo, Min Jin Go, Jian Jun Liu, Wei Gan, Ching-Chu Chen, Yong Gao, Shengxu Li, Nanette R Lee, Chen Wu, Xueya Zhou, Huaidong Song, Jie Yao, I-Te Lee, Jirong Long, Tatsuhiko Tsunoda, Koichi Akiyama, Naoyuki Takashima, Yoon Shin Cho, Rick Th Ong, Ling Lu, Chien-Hsiun Chen, Aihua Tan, Treva K Rice, Linda S Adair, Lixuan Gui, Matthew Allison, Wen-Jane Lee, Qiuyin Cai, Minoru Isomura, Satoshi Umemura, Young Jin Kim, Mark Seielstad, James Hixson, Yong-Bing Xiang, Masato Isono, Bong-Jo Kim, Xueling Sim, Wei Lu, Toru Nabika, Juyoung Lee, Wei-Yen Lim, Yu-Tang Gao, Ryoichi Takayanagi, Dae-Hee Kang, Tien Yin Wong, Chao Agnes Hsiung, I-Chien Wu, Jyh-Ming Jimmy Juang, Jiajun Shi, Bo Youl Choi, Tin Aung, Frank Hu, Mi Kyung Kim, Wei Yen Lim, Tzung-Dao Wang, Min-Ho Shin, Jeannette Lee, Bu-Tian Ji, Young-Hoon Lee, Terri L Young, Dong Hoon Shin, Byung-Yeol Chun, Myeong-Chan Cho, Bok-Ghee Han, Chii-Min Hwu, Themistocles L Assimes, Devin Absher, Xiaofei Yan, Eric Kim, Jane Z Kuo, Soonil Kwon, Kent D Taylor, Yii-Der I Chen, Jerome I Rotter, Lu Qi, Dingliang Zhu, Tangchun Wu, Karen L Mohlke, Dongfeng Gu, Zengnan Mo, Jer-Yuarn Wu, Xu Lin, Tetsuro Miki, E Shyong Tai, Jong-Young Lee, Norihiro Kato, Xiao-Ou Shu, Toshihiro Tanaka.
Hum. Mol. Genet.
PUBLISHED: 05-26-2014
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Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ?2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.
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Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-20-2014
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Insertions of the human-specific subfamily of LINE-1 (L1) retrotransposon are highly polymorphic across individuals and can critically influence the human transcriptome. We hypothesized that L1 insertions could represent genetic variants determining important human phenotypic traits, and performed an integrated analysis of L1 elements and single nucleotide polymorphisms (SNPs) in several human populations. We found that a large fraction of L1s were in high linkage disequilibrium with their surrounding genomic regions and that they were well tagged by SNPs. However, L1 variants were only partially captured by SNPs on standard SNP arrays, so that their potential phenotypic impact would be frequently missed by SNP array-based genome-wide association studies. We next identified potential phenotypic effects of L1s by looking for signatures of natural selection linked to L1 insertions; significant extended haplotype homozygosity was detected around several L1 insertions. This finding suggests that some of these L1 insertions may have been the target of recent positive selection.
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Prevalence and risk factors for retinopathy in persons without diabetes: the Singapore Indian Eye Study.
Acta Ophthalmol
PUBLISHED: 04-16-2014
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To describe prevalence and risk factors for retinopathy in an Asian Indian population without diabetes.
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Intracranial Stenosis, Cerebrovascular Diseases, and Cognitive Impairment in Chinese.
Alzheimer Dis Assoc Disord
PUBLISHED: 04-16-2014
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Extracranial carotid artery disease has been shown to be related to cognitive deficits. However, limited data are available on intracranial stenosis (ICS) and cognitive impairment. We investigate the association between ICS and cognitive impairment in Chinese. Subjects (n=278), recruited from the Epidemiology of Dementia in Singapore Study, underwent comprehensive clinical evaluation, neuropsychological testing, and brain magnetic resonance imaging (MRI), including 3-dimensional-time-of-flight magnetic resonance angiography (MRA). Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment no dementia and dementia were diagnosed according to internationally accepted diagnostic criteria. Linear and logistic regression models were adjusted for age, sex, education, vascular risk factors, and other MRI markers. A total of 29 (10.4%) persons had ICS on MRA, which was significantly associated with both composite cognitive Z-scores [mean difference in Z-score, presence vs. absence of ICS: -0.37 (95% confidence interval: -0.63, -0.12)] and specific domains including executive function, language, visuomotor speed, verbal memory, and visual memory. ICS was also related to significant cognitive impairment (odds ratio: 5.10 [1.24 to 21.02]). With respect to other MRI markers, adjusted for the presence of lacunar infarcts, the associations of ICS with both composite and domain-specific Z-scores, and significant cognitive impairment became nonsignificant; however, adjustment for other MRI markers did not alter these associations. In this Chinese population, presence of ICS was associated with cognitive impairment independent of vascular risk factors. These associations may be mediated through the presence of infarcts.
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Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.
Hum. Genet.
PUBLISHED: 04-14-2014
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To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.
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Microvascular network alterations in retina of subjects with cerebral small vessel disease.
Neurosci. Lett.
PUBLISHED: 04-13-2014
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Novel retinal imaging techniques have enabled the assessment of quantitative vascular parameters, which provide information on the microvasculature before the appearance of retinopathy signs. Advances in neuroimaging have revealed that cerebral microbleeds (CMB) - besides lacunar infarcts and white matter lesions (WML) - may be a novel marker of cerebral small vessel disease. We examine whether quantitative retinal vascular parameters are related to cerebral small vessel disease in a Chinese population. Participants from Epidemiology of Dementia in Singapore Study underwent comprehensive examinations, including 3-Tesla cranial magnetic resonance imaging and retinal-photography. Retinal vascular parameters (caliber, tortuosity, fractal dimension) were measured from photographs using a semi-automated computer-assisted program. Lacunar infarcts and CMB were visually graded. Total brain and WML volume were obtained using a validated segmentation tool. A total of 261 subjects were included, of whom 36 had lacunar infarcts, 29 had severe WML, and 83 had CMB. In age-sex-adjusted models, narrower retinal arteriolar caliber, wider venular caliber and smaller arteriolar fractal dimension were associated with presence of multiple CMB. In contrast, no association was found with lacunar infarcts and WML volume. After multivariate adjustments, associations of venular caliber, arteriolar fractal dimensions and arteriolar tortuosity with CMB remained statistically significant. In conclusion, subjects with early structural changes in retinal microvasculature were more likely to have CMBs, supporting hypothesis that CMB may be an early manifestation of cerebral small vessel disease.
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Prevalence and causes of vision loss in North Africa and the Middle East: 1990-2010.
Br J Ophthalmol
PUBLISHED: 03-03-2014
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To describe the prevalence and causes of visual impairment and blindness in North Africa and the Middle East (NAME) in 1990 and 2010.
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Comparison of exudative age-related macular degeneration subtypes in Japanese and French Patients: multicenter diagnosis with multimodal imaging.
Am. J. Ophthalmol.
PUBLISHED: 03-01-2014
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To compare and analyze differences and similarities between Japanese and French patients in subtype diagnosis of exudative age-related macular degeneration (AMD) as determined by fundus photography (FP) and fluorescein angiography (FA), and a multimodal imaging involving FP, FA, indocyanine green angiography (ICGA), and optical coherence tomography (OCT).
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Is chronic kidney disease associated with diabetic retinopathy in Asian adults? ?.
J Diabetes
PUBLISHED: 02-28-2014
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Diabetic nephropathy (DN) is commonly associated with diabetic retinopathy (DR). Few studies have demonstrated that chronic kidney disease (CKD) is associated with DR. However, it is not clear if CKD in the absence of albuminuria is associated with DR.
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Correlation of structural and electrophysiological changes in the retina of young high myopes.
Ophthalmic Physiol Opt
PUBLISHED: 02-26-2014
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Despite a high prevalence of myopia among young East Asian adults, there is a lack of data on the myopic retina structure-function relationship in this group. We examined the association between optical coherence tomography (OCT) and electroretinogram (ERG) measurements in highly myopic young Asian adults to provide this information and also determined if OCT can be used as an alternative screening tool to assess retinal function in young myopic adults.
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Health burden associated with visual impairment in Singapore: the Singapore epidemiology of eye disease study.
Ophthalmology
PUBLISHED: 02-23-2014
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To assess the impact of visual impairment (VI) on health-related quality of life and to compare the health burden of VI and other health conditions in Singapore.
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Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia.
Jeannette Simino, Gang Shi, Joshua C Bis, Daniel I Chasman, Georg B Ehret, Xiangjun Gu, Xiuqing Guo, Shih-Jen Hwang, Eric Sijbrands, Albert V Smith, Germaine C Verwoert, Jennifer L Bragg-Gresham, Gemma Cadby, Peng Chen, Ching-Yu Cheng, Tanguy Corre, Rudolf A de Boer, Anuj Goel, Toby Johnson, Chiea-Chuen Khor, , Carla Lluis-Ganella, Jian'an Luan, Leo-Pekka Lyytikäinen, Ilja M Nolte, Xueling Sim, Siim Sõber, Peter J van der Most, Niek Verweij, Jing Hua Zhao, Najaf Amin, Eric Boerwinkle, Claude Bouchard, Abbas Dehghan, Gudny Eiriksdottir, Roberto Elosua, Oscar H Franco, Christian Gieger, Tamara B Harris, Serge Hercberg, Albert Hofman, Alan L James, Andrew D Johnson, Mika Kähönen, Kay-Tee Khaw, Zoltan Kutalik, Martin G Larson, Lenore J Launer, Guo Li, Jianjun Liu, Kiang Liu, Alanna C Morrison, Gerjan Navis, Rick Twee-Hee Ong, George J Papanicolau, Brenda W Penninx, Bruce M Psaty, Leslie J Raffel, Olli T Raitakari, Kenneth Rice, Fernando Rivadeneira, Lynda M Rose, Serena Sanna, Robert A Scott, David S Siscovick, Ronald P Stolk, André G Uitterlinden, Dhananjay Vaidya, Melanie M van der Klauw, Ramachandran S Vasan, Eranga Nishanthie Vithana, Uwe Völker, Henry Völzke, Hugh Watkins, Terri L Young, Tin Aung, Murielle Bochud, Martin Farrall, Catharina A Hartman, Maris Laan, Edward G Lakatta, Terho Lehtimäki, Ruth J F Loos, Gavin Lucas, Pierre Meneton, Lyle J Palmer, Rainer Rettig, Harold Snieder, E Shyong Tai, Yik-Ying Teo, Pim van der Harst, Nicholas J Wareham, Cisca Wijmenga, Tien Yin Wong, Myriam Fornage, Vilmundur Gudnason, Daniel Levy, Walter Palmas, Paul M Ridker, Jerome I Rotter, Cornelia M van Duijn, Jacqueline C M Witteman, Aravinda Chakravarti, Dabeeru C Rao.
Am. J. Hum. Genet.
PUBLISHED: 02-22-2014
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Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ? 5 × 10(-8)) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10(-4)) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.
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Measurement of macular fractal dimension using a computer-assisted program.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 02-15-2014
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Macular diseases may be associated with an altered retinal vasculature. We describe and test new software for the measurement of retinal vascular fractal dimension to quantify the complexity of retinal vasculature at the macula (D mac) and to compare this with fractal dimension measured around the optic disc (D disc).
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Female reproductive factors and major eye diseases in Asian women -the Singapore Malay Eye Study.
Ophthalmic Epidemiol
PUBLISHED: 02-14-2014
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To examine the association of reproductive factors and major eye diseases, including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy and cataract, in Asian women.
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Ethnic differences of intraocular pressure and central corneal thickness: the Singapore Epidemiology of Eye Diseases study.
Ophthalmology
PUBLISHED: 02-07-2014
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To determine the ethnic differences in the distribution of intraocular pressure (IOP) and central corneal thickness (CCT) in a multi-ethnic Asian population by self-reported ethnicity and genetic ancestry.
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Prevalence, racial variations, and risk factors of age-related macular degeneration in Singaporean Chinese, Indians, and Malays.
Ophthalmology
PUBLISHED: 02-06-2014
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To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons.
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Ankle-brachial index, cognitive impairment and cerebrovascular disease in a chinese population.
Neuroepidemiology
PUBLISHED: 01-28-2014
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Previous studies have assessed the association between ankle-brachial index (ABI) and cognition, mainly using brief cognitive tests. We investigated whether ABI was associated with cognition independent of neuroimaging markers of cerebrovascular disease.
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Body mass index and preclinical kidney disease in Indian adults aged 40 years and above without chronic kidney disease.
Clin. Exp. Nephrol.
PUBLISHED: 01-22-2014
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Obesity is associated with diabetes and hypertension, two major risk factors for chronic kidney disease (CKD). Recently, it has been shown that obesity is associated with preclinical kidney disease defined by elevated levels of cystatin C among those without CKD in US adults. However, the association of obesity with cystatin C is not known in industrialized Asian populations.
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Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
, Anubha Mahajan, Min Jin Go, Weihua Zhang, Jennifer E Below, Kyle J Gaulton, Teresa Ferreira, Momoko Horikoshi, Andrew D Johnson, Maggie C Y Ng, Inga Prokopenko, Danish Saleheen, Xu Wang, Eleftheria Zeggini, Gonçalo R Abecasis, Linda S Adair, Peter Almgren, Mustafa Atalay, Tin Aung, Damiano Baldassarre, Beverley Balkau, Yuqian Bao, Anthony H Barnett, Inês Barroso, Abdul Basit, Latonya F Been, John Beilby, Graeme I Bell, Rafn Benediktsson, Richard N Bergman, Bernhard O Boehm, Eric Boerwinkle, Lori L Bonnycastle, Noel Burtt, Qiuyin Cai, Harry Campbell, Jason Carey, Stéphane Cauchi, Mark Caulfield, Juliana C N Chan, Li-Ching Chang, Tien-Jyun Chang, Yi-Cheng Chang, Guillaume Charpentier, Chien-Hsiun Chen, Han Chen, Yuan-Tsong Chen, Kee-Seng Chia, Manickam Chidambaram, Peter S Chines, Nam H Cho, Young Min Cho, Lee-Ming Chuang, Francis S Collins, Marylin C Cornelis, David J Couper, Andrew T Crenshaw, Rob M Van Dam, John Danesh, Debashish Das, Ulf de Faire, George Dedoussis, Panos Deloukas, Antigone S Dimas, Christian Dina, Alex S Doney, Peter J Donnelly, Mozhgan Dorkhan, Cornelia van Duijn, Josée Dupuis, Sarah Edkins, Paul Elliott, Valur Emilsson, Raimund Erbel, Johan G Eriksson, Jorge Escobedo, Tonu Esko, Elodie Eury, Jose C Florez, Pierre Fontanillas, Nita G Forouhi, Tom Forsén, Caroline Fox, Ross M Fraser, Timothy M Frayling, Philippe Froguel, Philippe Frossard, Yutang Gao, Karl Gertow, Christian Gieger, Bruna Gigante, Harald Grallert, George B Grant, Leif C Grrop, Chrisropher J Groves, Elin Grundberg, Candace Guiducci, Anders Hamsten, Bok-Ghee Han, Kazuo Hara, Neelam Hassanali, Andrew T Hattersley, Caroline Hayward, Asa K Hedman, Christian Herder, Albert Hofman, Oddgeir L Holmen, Kees Hovingh, Astradur B Hreidarsson, Cheng Hu, Frank B Hu, Jennie Hui, Steve E Humphries, Sarah E Hunt, David J Hunter, Kristian Hveem, Zafar I Hydrie, Hiroshi Ikegami, Thomas Illig, Erik Ingelsson, Muhammed Islam, Bo Isomaa, Anne U Jackson, Tazeen Jafar, Alan James, Weiping Jia, Karl-Heinz Jöckel, Anna Jonsson, Jeremy B M Jowett, Takashi Kadowaki, Hyun Min Kang, Stavroula Kanoni, Wen Hong L Kao, Sekar Kathiresan, Norihiro Kato, Prasad Katulanda, Kirkka M Keinanen-Kiukaanniemi, Ann M Kelly, Hassan Khan, Kay-Tee Khaw, Chiea-Chuen Khor, Hyung-Lae Kim, Sangsoo Kim, Young Jin Kim, Leena Kinnunen, Norman Klopp, Augustine Kong, Eeva Korpi-Hyövälti, Sudhir Kowlessur, Peter Kraft, Jasmina Kravic, Malene M Kristensen, S Krithika, Ashish Kumar, Jesus Kumate, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Vasiliki Lagou, Timo A Lakka, Claudia Langenberg, Cordelia Langford, Robert Lawrence, Karin Leander, Jen-Mai Lee, Nanette R Lee, Man Li, Xinzhong Li, Yun Li, Junbin Liang, Samuel Liju, Wei-Yen Lim, Lars Lind, Cecilia M Lindgren, Eero Lindholm, Ching-Ti Liu, Jian Jun Liu, Stéphane Lobbens, Jirong Long, Ruth J F Loos, Wei Lu, Jian'an Luan, Valeriya Lyssenko, Ronald C W Ma, Shiro Maeda, Reedik Mägi, Satu Mannisto, David R Matthews, James B Meigs, Olle Melander, Andres Metspalu, Julia Meyer, Ghazala Mirza, Evelin Mihailov, Susanne Moebus, Viswanathan Mohan, Karen L Mohlke, Andrew D Morris, Thomas W Mühleisen, Martina Müller-Nurasyid, Bill Musk, Jiro Nakamura, Eitaro Nakashima, Pau Navarro, Peng-Keat Ng, Alexandra C Nica, Peter M Nilsson, Inger Njølstad, Markus M Nöthen, Keizo Ohnaka, Twee Hee Ong, Katharine R Owen, Colin N A Palmer, James S Pankow, Kyong Soo Park, Melissa Parkin, Sonali Pechlivanis, Nancy L Pedersen, Leena Peltonen, John R B Perry, Annette Peters, Janini M Pinidiyapathirage, Carl G Platou, Simon Potter, Jackie F Price, Lu Qi, Venkatesan Radha, Loukianos Rallidis, Asif Rasheed, Wolfgang Rathman, Rainer Rauramaa, Soumya Raychaudhuri, N William Rayner, Simon D Rees, Emil Rehnberg, Samuli Ripatti, Neil Robertson, Michael Roden, Elizabeth J Rossin, Igor Rudan, Denis Rybin, Timo E Saaristo, Veikko Salomaa, Juha Saltevo, Maria Samuel, Dharambir K Sanghera, Jouko Saramies, James Scott, Laura J Scott, Robert A Scott, Ayellet V Segrè, Joban Sehmi, Bengt Sennblad, Nabi Shah, Sonia Shah, A Samad Shera, Xiao Ou Shu, Alan R Shuldiner, Gunnar Sigurđsson, Eric Sijbrands, Angela Silveira, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S Small, Wing Yee So, Alena Stančáková, Kari Stefansson, Gerald Steinbach, Valgerdur Steinthorsdottir, Kathleen Stirrups, Rona J Strawbridge, Heather M Stringham, Qi Sun, Chen Suo, Ann-Christine Syvänen, Ryoichi Takayanagi, Fumihiko Takeuchi, Wan Ting Tay, Tanya M Teslovich, Barbara Thorand, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Emmi Tikkanen, Joseph Trakalo, Elena Tremoli, Mieke D Trip, Fuu Jen Tsai, Tiinamaija Tuomi, Jaakko Tuomilehto, André G Uitterlinden, Adán Valladares-Salgado, Sailaja Vedantam, Fabrizio Veglia, Benjamin F Voight, Congrong Wang, Nicholas J Wareham, Roman Wennauer, Ananda R Wickremasinghe, Tom Wilsgaard, James F Wilson, Steven Wiltshire, Wendy Winckler, Tien Yin Wong, Andrew R Wood, Jer-Yuarn Wu, Ying Wu, Ken Yamamoto, Toshimasa Yamauchi, Mingyu Yang, Loïc Yengo, Mitsuhiro Yokota, Robin Young, Delilah Zabaneh, Fan Zhang, Rong Zhang, Wei Zheng, Paul Z Zimmet, David Altshuler, Donald W Bowden, Yoon Shin Cho, Nancy J Cox, Miguel Cruz, Craig L Hanis, Jaspal Kooner, Jong-Young Lee, Mark Seielstad, Yik Ying Teo, Michael Boehnke, Esteban J Parra, Jonh C Chambers, E Shyong Tai, Mark I McCarthy, Andrew P Morris.
Nat. Genet.
PUBLISHED: 01-17-2014
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To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
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Microvascular network alterations in the retina of patients with Alzheimer's disease.
Alzheimers Dement
PUBLISHED: 01-15-2014
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Although cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD), the cerebral microcirculation is difficult to visualize directly in vivo. Because the retina provides a noninvasive window to assess the microcirculation, we determined whether quantitatively measured retinal microvascular parameters are associated with AD.
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Comparison of CKD-EPI Cystatin C and Creatinine Glomerular Filtration Rate Estimation Equations in Asian Indians.
Int J Nephrol
PUBLISHED: 01-14-2014
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Background. Chronic kidney disease (CKD) is identified in the general population using estimated glomerular filtration rates (eGFR) calculated from a serum creatinine-based equation, the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation. Using serum cystatin C in combination may improve eGFR accuracy. We evaluated the new CKD-EPI equations incorporating cystatin C in a population of Asian Indians in classifying CKD across body mass index, diabetes, and hypertension status. Methods. We retrieved standardized serum creatinine and serum cystatin C data from a cohort of 2877 Asian Indians aged 40-80 years from the Singapore Indian Eye Study and calculated eGFR (in?mL/min/1.73?m(2)) with the new CKD-EPI equations and serum creatinine only equation. Results. The creatinine only equation mean eGFR (88 ± 17) was similar to using spline Log cystatin C (88 ± 22). The lowest mean eGFR (81 ± 21) was obtained with the spline Log cystatin C-age, sex, and weight equation. The creatinine only equation had the fewest participants (7.1%) with eGFR <60 and spline Log cystatin C-age, sex, and weight equation had the most (16.1%). Conclusions. Using serum cystatin C resulted in widely varying eGFR which significantly affected the classification of chronic kidney disease.
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Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis.
Lancet Glob Health
PUBLISHED: 01-03-2014
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Numerous population-based studies of age-related macular degeneration have been reported around the world, with the results of some studies suggesting racial or ethnic differences in disease prevalence. Integrating these resources to provide summarised data to establish worldwide prevalence and to project the number of people with age-related macular degeneration from 2020 to 2040 would be a useful guide for global strategies.
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Retinal vascular fractals and cognitive impairment.
Dement Geriatr Cogn Dis Extra
PUBLISHED: 01-01-2014
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Retinal microvascular network changes have been found in patients with age-related brain diseases such as stroke and dementia including Alzheimer's disease. We examine whether retinal microvascular network changes are also present in preclinical stages of dementia.
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Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci.
PLoS ONE
PUBLISHED: 01-01-2014
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Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p?=?1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value?=?9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.
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Complete blood count and retinal vessel calibers.
PLoS ONE
PUBLISHED: 01-01-2014
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The influence of hematological indices such as complete blood count on microcirculation is poorly understood. Retinal microvasculature can be directly visualized and vessel calibers are associated with a range of ocular and systemic diseases. We examined the association of complete blood count with retinal vessel calibers.
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Determinants of posterior corneal biometric measurements in a multi-ethnic Asian population.
PLoS ONE
PUBLISHED: 01-01-2014
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To describe the corneal and anterior segment determinants of posterior corneal arc length (PCAL) and posterior corneal curvature (PCC).
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A prospective study of treatment patterns and 1-year outcome of Asian age-related macular degeneration and polypoidal choroidal vasculopathy.
PLoS ONE
PUBLISHED: 01-01-2014
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To study the treatment patterns and visual outcome over one year in Asian patients with choroidal neovascular membrane secondary to age-related macular degeneration (AMD-CNV) and polypoidal choroidal vasculopathy (PCV).
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Systemic medical management of diabetic retinopathy.
Middle East Afr J Ophthalmol
PUBLISHED: 12-17-2013
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Diabetes mellitus (DM) has assumed epidemic proportions and as a consequence, diabetic retinopathy is expected to be a major societal problem across the world. Diabetic retinopathy (DR) affects the vision by way of proliferative disease that results in vitreous hemorrhage and traction retinal detachment or by way of diabetic maculopathy (DME). The present-day management of diabetic retinopathy revolves around screening the diabetics for evidence of retinopathy and treating the retinopathy with laser photocoagulation. DME is treated with laser photocoagulation and/or intra- vitreal injection of anti-vascular endothelial growth factor (VEGF) agents or steroids. Laser remains the mainstay of treatment and is potentially destructive. Systemic management aims at preventing or delaying the onset of retinopathy; reversing the early retinopathy; or delaying the progression of established retinopathy. Evidence from multiple studies has confirmed the protective role of rigid control of blood glucose and blood pressure. The evidence for lipid control versus maculopathy was less definitive. However, the use of fenofibrates (originally used for lowering serum lipids) has shown a benefit on both proliferative disease and maculopathy outside their lipid-lowering effect. Other drugs being tried are the Protein Kinase C (PKC) inhibitors, other peroxisome proliferator-activated receptors (PPAR) agonists, Forsoklin (which binds GLUT 1 receptor), minocycline (for its anti inflammatory effect), and Celecoxib (Cox-2 inhibitor).
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Sorting multiple classes in multi-dimensional ROC analysis: parametric and nonparametric approaches.
Biomarkers
PUBLISHED: 12-16-2013
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Abstract In large-scale data analysis, such as in a microarray study to identify the most differentially expressed genes, diagnostic tests are frequently used to classify and predict subjects into their different categories. Frequently, these categories do not have an intrinsic natural order even though the quantitative test results have a relative order. As identifying the correct order for a proper definition of accuracy measures is important for a high-dimensional receiver operating characteristic (ROC) analysis, we propose rigorous and automated approaches to sort out the multiple categories using simple summary statistics such as means and relative effects. We discuss the hypervolume under the ROC manifold (HUM), its dependence on the order of the test results and the minimum acceptable HUM values in a general multi-category classification problem. Using a leukemia data set and a liver cancer data set, we show how our approaches provide accurate screening results when we have a large number of tests.
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Determinants of macular thickness using spectral domain optical coherence tomography in healthy eyes: the singapore chinese eye study.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 11-14-2013
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We determined ocular and systemic factors influencing macular thickness measured by spectral-domain optical coherence tomography (SD-OCT) in a population-based sample of healthy eyes.
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Retinal vascular parameter variations in patients with human immunodeficiency virus.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 11-02-2013
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To compare the retinal vascular parameters in patients with human immunodeficiency virus (HIV) infection with normal controls, and to determine the relationship between retinal vascular parameters and HIV-related blood biomarkers (CD4(+) T-lymphocytes count, presence of HIV RNA).
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Relationship between retinal vascular geometry with retinal nerve fiber layer and ganglion cell-inner plexiform layer in nonglaucomatous eyes.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-19-2013
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To examine the relationship between retinal vascular geometric parameters with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) parameters in nonglaucomatous subjects.
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Self-assessment for optic disc segmentation.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Optic disc segmentation from retinal fundus image is a fundamental but important step in many applications such as automated glaucoma diagnosis. Very often, one method might work well on many images but fail on some other images and it is difficult to have a single method or model to cover all scenarios. Therefore, it is important to combine results from several methods to minimize the risk of failure. For this purpose, this paper computes confidence scores for three methods and combine their results for an optimal one. The experimental results show that the combined result from three methods is better than the results by any individual method. It reduces the mean overlapping error by 7.4% relatively compared with best individual method. Simultaneously, the number of failed cases with large overlapping errors is also greatly reduced. This is important to enhance the clinical deployment of the automated disc segmentation.
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Changes in retinal microvascular caliber precede the clinical onset of preeclampsia.
Hypertension
PUBLISHED: 09-09-2013
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Preeclampsia is a leading cause of maternal morbidity and mortality. The degree of maternal cardiovascular dysfunction that precedes the onset of preeclampsia is largely unknown. This prospective cohort study aimed to characterize differences in vivo in retinal microvascular caliber and blood pressure throughout pregnancy in relation to preeclampsia development. Women were recruited from Royal Prince Alfred Hospital, Sydney, Australia, of which 92 women were included in the study. Retinal images and blood pressures were collected at 13, 19, 29, and 38 weeks of gestation. Retinal vessels were analyzed as the central retinal arteriolar equivalent corrected for mean arterial blood pressure and the central retinal venular equivalent corrected for mean arterial blood pressure, using generalized linear models adjusted for age and body mass index. The preeclampsia group were significantly older (P=0.002) and had a significantly higher mean body mass index (P=0.005). The central retinal arteriolar equivalent corrected for mean arterial blood pressure was significantly reduced at 13 (P=0.03), 19 (P=0.007), and 38 (P=0.03) weeks of gestation in the preeclampsia group. The central retinal venular equivalent corrected for mean arterial blood pressure was also significantly lower at 13 (P=0.04) and 19 (P=0.001) weeks of gestation in the women who progressed to preeclampsia. This study directly documents increased peripheral resistance in vivo, observed as the combination of constricted retinal arterioles or venules and elevated blood pressure, in women who later developed preeclampsia. This difference preceded the clinical signs of preeclampsia.
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Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci.
Hypertension
PUBLISHED: 09-03-2013
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We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26,600 East Asian participants (stage 1) followed by replication study of up to 28,783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0×10(-8) in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected P<1.4×10(-3). No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at ATP2B1 (P=7.5×10(-15)), rs2681492 at ATP2B1 (P=3.4×10(-7)), rs11191593 at NT5C2 (1.1×10(-6)), rs3824755 at CYP17A1 (P=1.2×10(-6)), and rs13149993 at FGF5 (P=2.4×10(-4)). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and P<0.05), including rs319690 at MAP4 (P=0.014) and rs1173771 at NPR3 (P=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at ATP2B1 (P=1.2×10(-5)) and rs11191593 at NT5C2 (P=1.1×10(-3)), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1×10(-3)) and rs2681492 at ATP2B1 (P=9.0×10(-3)). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm?Hg for mean arterial pressure and from 0.03 to 0.21 mm?Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.
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Association of silent lacunar infarct with brain atrophy and cognitive impairment.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 08-09-2013
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Silent lacunar infarct (SLI) is associated with cognitive decline and linked to an increased risk of stroke and dementia. We examined the association of SLI with MRI measures of cortical thickness, subcortical and lateral ventricular shapes and cognition in 285 ethnic Chinese elderly.
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Comparison of the Montreal Cognitive Assessment and the Mini-Mental State Examination in detecting multi-domain mild cognitive impairment in a Chinese sub-sample drawn from a population-based study.
Int Psychogeriatr
PUBLISHED: 07-22-2013
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We examined the discriminant validity of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in detecting multiple-domain mild cognitive impairment (md-MCI) in a Chinese sub-sample drawn from elderly population-based study.
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Retinal microvascular changes and risk of stroke: the Singapore Malay Eye Study.
Stroke
PUBLISHED: 07-18-2013
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To examine the relationship between retinal microvascular measures and incident stroke in an Asian Malay population.
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Utility of EQ-5D to assess patients undergoing cataract surgery.
Optom Vis Sci
PUBLISHED: 07-16-2013
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To assess the construct validity and responsiveness of the EuroQoL-5D (EQ-5D) instrument in Asian patients undergoing cataract surgery in Singapore.
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Quantitative measurement of hard exudates in patients with diabetes and their associations with serum lipid levels.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 07-13-2013
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To describe a reproducible method of quantifying macular hard exudates (HEs) in diabetic maculopathy and determine the associations of HEs with systemic risk factors.
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Kidney and eye diseases: common risk factors, etiological mechanisms, and pathways.
Kidney Int.
PUBLISHED: 07-03-2013
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Chronic kidney disease is an emerging health problem worldwide. The eye shares striking structural, developmental, and genetic pathways with the kidney, suggesting that kidney disease and ocular disease may be closely linked. A growing number of studies have found associations of chronic kidney disease with age-related macular degeneration, diabetic retinopathy, glaucoma, and cataract. In addition, retinal microvascular parameters have been shown to be predictive of chronic kidney disease. Chronic kidney disease shares common vascular risk factors including diabetes, hypertension, smoking, and obesity, and pathogenetic mechanisms including inflammation, oxidative stress, endothelial dysfunction, and microvascular dysfunction, with ocular diseases supporting the Common Soil Hypothesis. In this review, we present major epidemiological evidence for these associations and explore underlying pathogenic mechanisms and common risk factors for kidney and ocular disease. Understanding the link between kidney and ocular disease can lead to the development of new treatment and screening strategies for both diseases.Kidney International advance online publication, 11 December 2013; doi:10.1038/ki.2013.491.
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A new community-based outdoor intervention to increase physical activity in Singapore children: findings from focus groups.
Ann. Acad. Med. Singap.
PUBLISHED: 06-18-2013
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Myopia is a significant public health problem in Singapore with estimates that more than 50% of the population is affected by it by the time of adulthood. Childhood obesity is also increasing and has been linked to long-term health problems. Recent studies have found that Singaporean children in Primary 1 spend less than 3 hours a day outdoors which is less than children in other countries. Physical activity has been shown to be protective against obesity and recently, there has been some evidence to suggest that time spent outdoors may reduce the prevalence and severity of myopia. This study aims to explore the barriers and enablers to children in Singapore participating in outdoor activities.
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Pathologic changes in highly myopic eyes of young males in Singapore.
Ann. Acad. Med. Singap.
PUBLISHED: 06-18-2013
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This study describes the pathologic changes in the retina of a group of young Asian subjects with myopia worse than -10 diopters spherical equivalent (SE) refraction.
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No association of 9p21 with arterial elasticity and retinal microvascular findings.
Atherosclerosis
PUBLISHED: 06-06-2013
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How 9p21 variation affects risk of cardiovascular disease is unclear, so we assessed whether 9p21 variants are associated with arterial elasticity or retinal microvascular findings.
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Myopia, axial length, and age-related cataract: the Singapore Malay eye study.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 06-06-2013
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To describe the associations of myopia and axial length (AL) with age-related cataract in an Asian population in Singapore.
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Microvascular structure and network in the retina of patients with ischemic stroke.
Stroke
PUBLISHED: 05-28-2013
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Microvascular disease has been implicated in the pathogenesis of stroke. The retina provides a window to assess microcirculation noninvasively. We studied the association between quantitatively measured retinal microvascular characteristics and acute ischemic stroke.
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Racial differences in retinal vessel geometric characteristics: a multiethnic study in healthy Asians.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 05-09-2013
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To investigate potential racial/ethnic differences in retinal vascular geometric parameters in a multiethnic Asian population (Chinese, Malay, and Indian) free of clinical diseases.
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Structural changes in the retinal microvasculature and renal function.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 04-11-2013
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To evaluate the associations between chronic kidney disease (CKD) and microalbuminuria, and a comprehensive range of retinal microvascular abnormalities including traditional and new retinal vascular measures.
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Combined genotype and haplotype tests for region-based association studies.
BMC Genomics
PUBLISHED: 04-09-2013
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Although single-SNP analysis has proven to be useful in identifying many disease-associated loci, region-based analysis has several advantages. Empirically, it has been shown that region-based genotype and haplotype approaches may possess much higher power than single-SNP statistical tests. Both high quality haplotypes and genotypes may be available for analysis given the development of next generation sequencing technologies and haplotype assembly algorithms.
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Ethnic differences in the association between blood pressure components and chronic kidney disease in middle aged and older Asian adults.
BMC Nephrol
PUBLISHED: 04-07-2013
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Chronic kidney disease (CKD) is an emerging public health problem worldwide. Previous studies have shown an association between blood pressure (BP) and CKD. However, it is not clear if there are ethnic differences in this association. We examined the association between BP and CKD in a multi-ethnic Asian population in Singapore.
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Management Paradigms for Diabetic Macular Edema.
Am. J. Ophthalmol.
PUBLISHED: 04-05-2013
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To provide evidence-based recommendations for diabetic macular edema (DME) management based on updated information from publications on DME treatment modalities.
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Vitamin D deficiency is not associated with changes in retinal geometric parameters in young people with type 1 diabetes.
J Diabetes Res
PUBLISHED: 01-12-2013
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Changes in retinal geometric parameters predict risk and progression of diabetic retinopathy (DR). We have shown that vitamin D deficiency (VDD) is associated with DR. We hypothesized that VDD mediates changes in retinal geometric parameters. Retinal vascular geometric parameters were assessed using a semiautomated computer program in photographs from young people with type 1 diabetes (T1D) (n = 481) and summarized as central retinal arteriolar and venular equivalents (CRAE, CRVE), fractal dimension, length-diameter ratio, branching angle and curvature tortuosity. Parameters were compared between those with and without DR and VDD (25-hydroxyvitamin D concentration ? 50?nmol/L). Retinal vascular geometric parameters were also compared across quartiles of vitamin D levels. Median CRVE was higher in patients with DR compared with those without (median (IQR) CRVE 247.3? ? m (31.3) versus 238.8? ? m (23.5), P = 0.01). Fractal dimension was marginally greater in patients without VDD (1.49 (0.06) versus 1.47 (0.07) P = 0.03). There was no difference in CRAE, CRVE, length-diameter ratio, branching angle, and curvature tortuosity between those with and without VDD and across quartiles of 25OHD. In conclusion, DR is associated with higher CRVE in young people with T1D; however, VDD is not associated with changes in retinal vascular geometric measures, suggesting an earlier role in the time course of DR pathogenesis.
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Fenofibrate: a new treatment for diabetic retinopathy. Molecular mechanisms and future perspectives.
Curr. Med. Chem.
PUBLISHED: 01-04-2013
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Despite improving standards of care, people with diabetes remain at risk of development and progression of diabetic retinopathy (DR) and visual impairment. Identifying novel therapeutic approaches, preferably targeting more than one pathogenic pathway in DR, and at an earlier stage of disease, is attractive. There is now consistent evidence from two major trials, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study and the Action to Control Cardiovascular Risk in Diabetes Eye (ACCORD-Eye) study, totalling 11,388 people with type 2 diabetes (5,701 treated with fenofibrate) that fenofibrate reduces the risk of development and progression of DR. Therefore, fenofibrate may be considered a preventive strategy for patients without DR or early intervention strategy for those with mild DR. A number of putative therapeutic mechanisms for fenofibrate, both dependent and independent of lipids, have been proposed. A deeper understanding of the mode of action of fenofibrate will further help to define how best to use fenofibrate clinically as an adjunct to current management of DR.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.