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Find video protocols related to scientific articles indexed in Pubmed.
Serum homocysteine, vitamin B12 and folate and the prevalence and incidence of posterior subcapsular cataract.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 11-20-2014
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Purpose: We assessed associations between serum levels of homocysteine, vitamin B12 and folate and the prevalence and 5-year incidence of posterior subcapsular (PSC) cataract in Blue Mountains Eye Study participants. Methods: We examined 3508 participants aged 49+ years during 1997-2000, including 2335 (75.1% of survivors) original and 1174 (85.2% of those eligible) newly recruited subjects. Five years later (2002-2004), 1952 (76.6% of survivors) original participants were re-examined. Detailed examinations, including lens photographs and fasting blood tests, were conducted at both visits. Logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) after multivariable adjustment. Results: In this population, those with PSC were older, less likely to have higher education and more likely to have diabetes and myopia. PSC prevalence was 5.7% (150/2644). Higher levels of homocysteine (per standard deviation (SD), OR 1.17, 95% CI 1.00-1.37,) and lower levels of folate (per SD, OR 1.24, 95% CI 0.99-1.56) were associated with prevalent PSC. There was significant interaction (p<0.05) between vitamin B12 and homocysteine; for B12 ?125pmol/l, 28% higher PSC prevalence was associated with homocysteine (per SD, OR 1.28, 95% CI 1.09-1.52), however, for B12 <125pmol/l, non-significant lower PSC prevalence was associated with homocysteine (per SD, OR 0.16, 95% CI 0.02-1.57). 5-year PSC incidence was 5.7% (n=59/1030) with no significant associations with homocysteine, B12 and folate. Conclusions: Higher serum homocysteine level was associated with PSC cataract prevalence in this population. Vitamin B12 status seemed to modify this association. Lack of longitudinal association could have resulted from insufficient study power.
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Visual Impairment and the Incidence of Falls and Fractures among Older People: Longitudinal findings from the Blue Mountains Eye Study.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 11-06-2014
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Purpose: To assess the impact of visual impairment on the incidence of falls and fractures in older persons. Methods: Of 3654 baseline participants, 2334, 1952 and 1149 were re-examined after 5, 10 and 15-years. Presenting visual acuity (VA) was measured at each examination. Bilateral and unilateral visual impairment was defined as VA <20/40 in the better eye and worse eye, respectively. Incident visual impairment was defined in eyes with VA ?20/40 at baseline which subsequently developed visual impairment. The incidence of falls was assessed over the 12-month period prior to each visit; whereas incidence of fractures were assessed over the 5-year period between the two visits. Discrete logistic-regression models with time-dependant variables were used to assess associations between visual impairment and subsequent falls and fractures after adjusting for co-factors. Results: The proportions of participants reporting ?2 falls ranged 10%-14%, and proportions reporting fractures ranged 12%-21%, across the three follow-up visits. Participants with incident visual impairment were more likely to report ?2 falls in 5 years, OR 1.46, 95% CI 1.04-2.04 (bilateral visual impairment) and OR 1.22, 95% CI 0.98-1.51 (unilateral). Compared to participant with normal vision, those with incident unilateral visual impairment had a higher incidence of fractures over 5 years (OR 1.27, 95%CI 0.98-1.51). No increased incidence of falls or fractures was evident after 5+ years among participants with any visual impairment. Conclusions: In this older cohort, more recent development of visual impairment was associated with increased likelihood of subsequent falls and fractures in the next 5 years, independent of co-morbidities.
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Polygenic Overlap Between Kidney Function and Large Artery Atherosclerotic Stroke.
Stroke
PUBLISHED: 10-30-2014
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Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes.
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Decreased retinal capillary flow is not a mediator of the protective myopia-diabetic retinopathy relationship.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-02-2014
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The mechanisms supporting the protective relationship between a longer axial length (AL) and a decreased risk of diabetic retinopathy (DR) remain unclear. Previous studies have demonstrated reduced retinal blood flow in axial myopia, and it has been suggested that the compromised retinal capillaries in diabetes are less likely to leak and rupture as a result of this decreased flow. In this study, we therefore investigated if reduced retinal capillary flow (RCF) is a potential mechanism underpinning this protective relationship.
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METABOLIC SYNDROME AND RISK OF AGE-RELATED MACULAR DEGENERATION.
Retina (Philadelphia, Pa.)
PUBLISHED: 09-11-2014
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To investigate the relationship between metabolic syndrome (MetS) and its components with the risk of early- and late-stage age-related macular degeneration (AMD).
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Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.
Nat. Genet.
PUBLISHED: 08-31-2014
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Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.
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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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Association of Open-Angle Glaucoma Loci With Incident Glaucoma in the Blue Mountains Eye Study.
Am. J. Ophthalmol.
PUBLISHED: 06-27-2014
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To determine if open-angle glaucoma (OAG)-associated single nucleotide polymorphisms (SNPs) are associated with incident glaucoma and if such genetic information is useful in OAG risk prediction.
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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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Is renal function associated with early age-related macular degeneration?
Optom Vis Sci
PUBLISHED: 06-01-2014
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Age-related macular degeneration (AMD) and chronic kidney disease both involve immune dysregulation and may share underlying pathophysiologic changes to systemic homeostasis. Hence, we aim to evaluate associations between impaired kidney function and early AMD, in a search for urinary biomarkers for AMD.
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Improving access to hearing services for people with low vision: piloting a "hearing screening and education model" of intervention.
Ear Hear
PUBLISHED: 05-24-2014
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The aims of this study were to investigate the potential unmet need for hearing services among older people attending low-vision rehabilitation, and pilot a "Hearing Screening and Education Model" (HSEM) of intervention to promote use of hearing services and aids among these individuals.
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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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Body mass index and retinopathy in Asian populations with diabetes mellitus.
Acta Diabetol
PUBLISHED: 03-30-2014
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Body mass index (BMI) is an established risk factor for diabetes. However, the association between BMI and diabetic retinopathy (DR) has been inconclusive. We aimed to assess the association between BMI and DR in a large population-based sample of multi-ethnic Asian adults in Singapore. We examined 2,278 adults aged ?40 years with diabetes who participated in three population-based studies conducted from 2004 to 2011: the Singapore Malay Eye Study, the Singapore Indian Eye Study, and the Singapore Chinese Eye Study. Retinal photographs taken from both eyes were graded for any and vision-threatening (VTDR) using the modified Airlie House Classification. BMI (kg/m(2)) was categorized into normal/underweight (<25), overweight (25-29.9), and obese (?30). The prevalence rates of any and VTDR in the study population were 35.1 % and 9.1 %, respectively. The prevalence of any and VTDR decreased with increasing categories of BMI (P trend <0.001 and 0.005). In multivariable models adjusted for potential confounders, compared to those with normal weight, the odds ratio (95 % confidence interval) of any DR was 0.71 (0.57-0.88) for overweight and 0.70 (0.53-0.92) for obese. Corresponding estimates for VTDR were 0.84 (0.59-1.21) for overweight and 0.58 (0.35-0.94) for obese. The inverse association between BMI and any DR was consistently present when BMI was analyzed as a continuous variable and in analyses stratified by ethnicity and age. In a population-based sample of multi-ethnic Asian adults, BMI levels were inversely associated with any DR and VTDR.
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Vitreous biomarkers in diabetic retinopathy: a systematic review and meta-analysis.
J. Diabetes Complicat.
PUBLISHED: 03-18-2014
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The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular pathway interactions of these markers found to be consistently associated with DR. Relevant databases [PubMed and ISI web of science] were searched for all published articles investigating molecular biomarkers of the vitreous associated with DR. Based on set exclusion/inclusion criteria available data from studies with human vitreous samples were extracted and used for our meta-analysis. The interactions of significant biomarkers in DR were investigated via STRING and KEGG pathway analysis. Our meta-analysis of DR identifies eleven biomarkers as potential therapeutic candidates alternate to current anti-VEGF therapy. Four of these are deemed viable therapeutic targets for PDR; ET receptors (ET A and ET B), anti-PDGF-BB, blocking TGF-? using cell therapy and PEDF. The identification of supplementary or synergistic therapeutic candidates to anti VEGF in the treatment of DR may aid in the development of future treatment trials.
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Association of serum lipids with macular thickness and volume in type 2 diabetes without diabetic macular edema.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 02-27-2014
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To assess the relationship between macular thickness and volume as characterized by optical coherence tomography (OCT) and known risk factors for diabetic retinopathy (DR) or macular edema (DME) in type 2 diabetic patients with no DME.
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Associations of retinal oximetry in persons with diabetes.
Clin. Experiment. Ophthalmol.
PUBLISHED: 02-26-2014
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There are limited data available on the variables that might affect retinal vessel oxygen saturation (SO2 ) in diabetes. Therefore, the aim of this study is to assess factors associated with retinal oximetry values in persons with diabetes.
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Adherence to dietary guidelines and the 10-year cumulative incidence of visual impairment: the Blue Mountains Eye Study.
Am. J. Ophthalmol.
PUBLISHED: 02-24-2014
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To assess whether adherence to dietary guidelines at baseline is associated with the incidence of visual impairment among older persons after 10 years.
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Replication of genetic loci implicated in diabetic retinopathy.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 02-15-2014
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Recent genome-wide association studies for diabetic retinopathy (DR) have identified novel single nucleotide polymorphisms (SNPs) associated with this potentially blinding disease. These markers could prove useful in risk profiling, if the association are validated by replication. To date, these associations have not been well assessed in independent cohorts. The objective of this study was to ascertain any association of these polymorphisms with advanced stages of DR.
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Associations of retinal oximetry in healthy young adults.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 02-15-2014
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To assess factors associated with retinal oximetry values in healthy young adults.
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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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Consumption of dairy products and the 15-year incidence of age-related macular degeneration.
Br. J. Nutr.
PUBLISHED: 02-06-2014
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Habitual consumption of dairy products has been shown to play an important role in the prevention of several chronic diseases. We aimed to prospectively assess the relationship between the change in dairy product consumption (both regular fat and low/reduced fat) and the 15-year incidence of age-related macular degeneration (AMD). In the Blue Mountains Eye Study, 2037 participants aged 49 years or above at baseline were re-examined at follow-up in 1997-9, 2002-4 and/or 2007-9. AMD was assessed from retinal photographs. Dietary data were collected using a semi-quantitative FFQ, and servings of dairy product consumption calculated. Over the 15-year follow-up, there were 352, 268 and eighty-four incident cases of any, early and late AMD, respectively. After adjusting for age, sex, current smoking, white cell count and fish consumption, a significant linear trend (P for trend = 0·003) was observed with decreasing consumption of total dairy foods and the 15-year incidence of late AMD, comparing the lowest v. highest quintile of intake (OR 2·80, 95 % CI 1·21, 3·04). Over the 15 years, decreased consumption of reduced-fat dairy foods was associated with an increased risk of incident late AMD, comparing the lowest to highest quintile of intake (OR 3·10, 95 % CI 1·18, 8·14, P for trend = 0·04). Decreasing total dietary Ca intake over the 15 years was also associated with an increased risk of developing incident late AMD (multivariable-adjusted P for trend = 0·03). A lower consumption of dairy products (regular and low fat) and Ca was independently associated with a higher risk of developing incident late AMD in the long term. Additional cohort studies are needed to confirm these findings.
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Harmonizing the classification of age-related macular degeneration in the three-continent AMD consortium.
Ophthalmic Epidemiol
PUBLISHED: 01-29-2014
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To describe methods to harmonize the classification of age-related macular degeneration (AMD) phenotypes across four population-based cohort studies: the Beaver Dam Eye Study (BDES), the Blue Mountains Eye Study (BMES), the Los Angeles Latino Eye Study (LALES), and the Rotterdam Study (RS).
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Clarifying the role of ATOH7 in glaucoma endophenotypes.
Br J Ophthalmol
PUBLISHED: 01-23-2014
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The ATOH7 gene has been previously associated with glaucoma and glaucoma-related traits, such as disc size and cup/disc ratio (CDR). CDR is an important part of the glaucoma phenotype, whereas the relationship between the disc size and the disease is not well understood. The aim of this study was to investigate whether ATOH7 is associated independently with CDR or merely with the size of the optic disc.
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Fluid intake and all-cause mortality, cardiovascular mortality and kidney function: a population-based longitudinal cohort study.
Nephrol. Dial. Transplant.
PUBLISHED: 01-06-2014
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Drinking eight glasses of fluid or water each day is widely believed to improve health, but evidence is sparse and conflicting. We aimed to investigate the association between fluid consumption and long-term mortality and kidney function.
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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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Impact of measurement error on testing genetic association with quantitative traits.
PLoS ONE
PUBLISHED: 01-01-2014
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Measurement error of a phenotypic trait reduces the power to detect genetic associations. We examined the impact of sample size, allele frequency and effect size in presence of measurement error for quantitative traits. The statistical power to detect genetic association with phenotype mean and variability was investigated analytically. The non-centrality parameter for a non-central F distribution was derived and verified using computer simulations. We obtained equivalent formulas for the cost of phenotype measurement error. Effects of differences in measurements were examined in a genome-wide association study (GWAS) of two grading scales for cataract and a replication study of genetic variants influencing blood pressure. The mean absolute difference between the analytic power and simulation power for comparison of phenotypic means and variances was less than 0.005, and the absolute difference did not exceed 0.02. To maintain the same power, a one standard deviation (SD) in measurement error of a standard normal distributed trait required a one-fold increase in sample size for comparison of means, and a three-fold increase in sample size for comparison of variances. GWAS results revealed almost no overlap in the significant SNPs (p<10(-5)) for the two cataract grading scales while replication results in genetic variants of blood pressure displayed no significant differences between averaged blood pressure measurements and single blood pressure measurements. We have developed a framework for researchers to quantify power in the presence of measurement error, which will be applicable to studies of phenotypes in which the measurement is highly variable.
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Dual Sensory Impairment and Hearing Aid Use Among Clients Attending Low-Vision Services in Australia: The Vision-Hearing Project.
J Aging Health
PUBLISHED: 12-15-2013
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To report the frequency of hearing impairment among vision rehabilitation clients, and to identify patterns of hearing service and aid use.
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An update on the molecular actions of fenofibrate and its clinical effects on diabetic retinopathy and other microvascular end points in patients with diabetes.
Diabetes
PUBLISHED: 11-23-2013
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The drug fenofibrate has received major attention as a novel medical treatment for diabetic retinopathy (DR) and other diabetes-induced microvascular complications. This interest stems from two recent large, well-designed clinical trials that demonstrated large reductions in the progression of DR and the need for laser intervention, in addition to a reduction in renal and neurological outcomes, in patients with type 2 diabetes. In both trials, the greatest benefit on DR progression was observed in those patients with DR at baseline. Originally considered a lipid-modifying drug, it now appears that multiple mechanisms may underpin the benefit of fenofibrate on diabetic microvascular end points. Fenofibrate regulates the expression of many different genes, with a range of beneficial effects on lipid control, inflammation, angiogenesis, and cell apoptosis. These factors are believed to be important in the development of DR regardless of the underlying diabetes etiology. Cell experiments have demonstrated improved survival of retinal endothelial and pigment epithelial cells in conjunction with reduced stress signaling under diabetic conditions. Further, fenofibrate improves retinal outcomes in rodent models of diabetes and retinal neovascularization. Given the results of these preclinical studies, further clinical trials are needed to establish the benefits of fenofibrate in other forms of diabetes, including type 1 diabetes. In DR management, fenofibrate could be a useful adjunctive treatment to modifiable risk factor control and regular ophthalmic review. Its incorporation into clinical practice should be continually revised as more information becomes available.
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Retinal arteriolar dilation to flicker light is reduced on short-term retesting.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-31-2013
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To investigate the impact of retesting frequency over a short period on flicker light-induced retinal vasodilation.
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Axial length, retinal function, and oxygen consumption: a potential mechanism for a lower risk of diabetic retinopathy in longer eyes.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-31-2013
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To determine the relationship between axial length (AL), retinal function, and relative oxygen (O?) consumption to better understand the protective effect of axial elongation on diabetic retinopathy development.
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Common variants in mendelian kidney disease genes and their association with renal function.
Afshin Parsa, Christian Fuchsberger, Anna Köttgen, Conall M O'Seaghdha, Cristian Pattaro, Mariza de Andrade, Daniel I Chasman, Alexander Teumer, Karlhans Endlich, Matthias Olden, Ming-Huei Chen, Adrienne Tin, Young J Kim, Daniel Taliun, Man Li, Mary Feitosa, Mathias Gorski, Qiong Yang, Claudia Hundertmark, Meredith C Foster, Nicole Glazer, Aaron Isaacs, Madhumathi Rao, Albert V Smith, Jeffrey R O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Shih-Jen Hwang, Elizabeth J Atkinson, Kurt Lohman, Marilyn C Cornelis, Asa Johansson, Anke Tönjes, Abbas Dehghan, Vincent Couraki, Elizabeth G Holliday, Rossella Sorice, Zoltan Kutalik, Terho Lehtimäki, Tonu Esko, Harshal Deshmukh, Sheila Ulivi, Audrey Y Chu, Federico Murgia, Stella Trompet, Medea Imboden, Barbara Kollerits, Giorgio Pistis, Tamara B Harris, Lenore J Launer, Thor Aspelund, Gudny Eiriksdottir, Braxton D Mitchell, Eric Boerwinkle, Helena Schmidt, Edith Hofer, Frank Hu, Ayse Demirkan, Ben A Oostra, Stephen T Turner, Jingzhong Ding, Jeanette S Andrews, Barry I Freedman, Franco Giulianini, Wolfgang Koenig, Thomas Illig, Angela Döring, H-Erich Wichmann, Lina Zgaga, Tatijana Zemunik, Mladen Boban, Cosetta Minelli, Heather E Wheeler, Wilmar Igl, Ghazal Zaboli, Sarah H Wild, Alan F Wright, Harry Campbell, David Ellinghaus, Ute Nöthlings, Gunnar Jacobs, Reiner Biffar, Florian Ernst, Georg Homuth, Heyo K Kroemer, Matthias Nauck, Sylvia Stracke, Uwe Völker, Henry Völzke, Peter Kovacs, Michael Stumvoll, Reedik Mägi, Albert Hofman, André G Uitterlinden, Fernando Rivadeneira, Yurii S Aulchenko, Ozren Polašek, Nick Hastie, Veronique Vitart, Catherine Helmer, Jie Jin Wang, Bénédicte Stengel, Daniela Ruggiero, Sven Bergmann, Mika Kähönen, Jorma Viikari, Tiit Nikopensius, Michael Province, Helen Colhoun, Alex Doney, Antonietta Robino, Bernhard K Krämer, Laura Portas, Ian Ford, Brendan M Buckley, Martin Adam, Gian-Andri Thun, Bernhard Paulweber, Margot Haun, Cinzia Sala, Paul Mitchell, Marina Ciullo, Peter Vollenweider, Olli Raitakari, Andres Metspalu, Colin Palmer, Paolo Gasparini, Mario Pirastu, J Wouter Jukema, Nicole M Probst-Hensch, Florian Kronenberg, Daniela Toniolo, Vilmundur Gudnason, Alan R Shuldiner, Josef Coresh, Reinhold Schmidt, Luigi Ferrucci, Cornelia M van Duijn, Ingrid Borecki, Sharon L R Kardia, Yongmei Liu, Gary C Curhan, Igor Rudan, Ulf Gyllensten, James F Wilson, Andre Franke, Peter P Pramstaller, Rainer Rettig, Inga Prokopenko, Jacqueline Witteman, Caroline Hayward, Paul M Ridker, Murielle Bochud, Iris M Heid, David S Siscovick, Caroline S Fox, W Linda Kao, Carsten A Böger.
J. Am. Soc. Nephrol.
PUBLISHED: 09-12-2013
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Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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Relative Energy Balance, CKD, and Risk of Cardiovascular and All-Cause Mortality.
Am. J. Kidney Dis.
PUBLISHED: 08-30-2013
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Mortality risk for people with chronic kidney disease is substantially greater than that for the general population, increasing to a 7-fold greater risk for those on dialysis therapy. Higher body mass index, generally due to higher energy intake, appears protective for people on dialysis therapy, but the relationship between energy intake and survival in those with reduced kidney function is unknown.
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Visual impairment corrected via cataract surgery and 5-year survival in a prospective cohort.
Am. J. Ophthalmol.
PUBLISHED: 08-10-2013
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To compare mortality risk between cataract surgical patients with corrected and persistent visual impairment.
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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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Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 07-09-2013
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Keratoconus is a common complex corneal ectasia that can lead to severe visual impairment. Although a genetic component is well recognized, the genetic risk factors for keratoconus are yet to be fully elucidated. A recent genome-wide association study (GWAS) by Li et al. identified 15 potentially associated single nucleotide polymorphisms (SNPs). Here, we aimed to replicate these associations, and conduct a meta-analysis of the current and previous studies.
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An automated method for retinal arteriovenous nicking quantification from color fundus images.
IEEE Trans Biomed Eng
PUBLISHED: 06-25-2013
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Retinal arteriovenous (AV) nicking is one of the prominent and significant microvascular abnormalities. It is characterized by the decrease in the venular caliber at both sides of an artery-vein crossing. Recent research suggests that retinal AV nicking is a strong predictor of eye diseases such as branch retinal vein occlusion and cardiovascular diseases such as stroke. In this study, we present a novel method for objective and quantitative AV nicking assessment. From the input retinal image, the vascular network is first extracted using the multiscale line detection method. The crossover point detection method is then performed to localize all AV crossing locations. At each detected crossover point, the four vessel segments, two associated with the artery and two associated with the vein, are identified and two venular segments are then recognized through the artery-vein classification method. The vessel widths along the two venular segments are measured and analyzed to compute the AV nicking severity of that crossover. The proposed method was validated on 47 high-resolution retinal images obtained from two population-based studies. The experimental results indicate a strong correlation between the computed AV nicking values and the expert grading with a Spearman correlation coefficient of 0.70. Sensitivity was 77% and specificity was 92% (Kappa ? = 0.70) when comparing AV nicking detected using the proposed method to that detected using a manual grading method, performed by trained photographic graders.
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Incidence and Progression of Reticular Drusen in Age-Related Macular Degeneration: Findings from an Older Australian Cohort.
Ophthalmology
PUBLISHED: 06-21-2013
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To assess the 15-year incidence and progression of reticular drusen and associations of this lesion with age-related macular degeneration (AMD) risk factors.
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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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The prevalence of and risk factors associated with pterygium in a rural adult Chinese population: the Handan Eye Study.
Ophthalmic Epidemiol
PUBLISHED: 05-10-2013
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To describe the prevalence and risk factors for pterygium in a rural adult Chinese population.
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Myopia and the long-term incidence of cataract and cataract surgery: the Blue Mountains Eye Study.
Clin. Experiment. Ophthalmol.
PUBLISHED: 05-05-2013
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To assess the association between refractive errors and the 10-year incidence of cataract and cataract surgery.
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Homocysteine, folate, vitamin B-12, and 10-y incidence of age-related macular degeneration.
Am. J. Clin. Nutr.
PUBLISHED: 05-01-2013
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Epidemiologic evidence of a relation between serum total homocysteine (tHcy), vitamin B-12, and folate and age-related macular degeneration (AMD) is inconsistent and unresolved.
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Myopia and age-related cataract: a systematic review and meta-analysis.
Am. J. Ophthalmol.
PUBLISHED: 04-19-2013
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To examine if myopia is a risk factor for age-related cataract.
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The prognostic role of body mass index on mortality amongst the middle-aged and elderly: A competing risk analysis.
Diabetes Res. Clin. Pract.
PUBLISHED: 04-12-2013
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To determine the relationship between body mass index (BMI) including its 5-year changes and mortality, and compare the results obtained using Cox and competing risks models.
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Prediction of age-related macular degeneration in the general population: the Three Continent AMD Consortium.
Ophthalmology
PUBLISHED: 04-09-2013
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Prediction models for age-related macular degeneration (AMD) based on case-control studies have a tendency to overestimate risks. The aim of this study is to develop a prediction model for late AMD based on data from population-based studies.
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Three-Year Incidence and Factors Associated With Posterior Capsule Opacification After Cataract Surgery: The Australian Prospective Cataract Surgery and Age-related Macular Degeneration Study.
Am. J. Ophthalmol.
PUBLISHED: 04-02-2013
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To assess 3-year incidence and associated factors of posterior capsule opacification (PCO) after phacoemulsification surgery.
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Visual impairment and subsequent use of support services among older people: longitudinal findings from the Blue Mountains Eye Study.
Am. J. Ophthalmol.
PUBLISHED: 03-31-2013
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To assess the impact of visual impairment and blindness on the incident use of community support services in the Blue Mountains Eye Study.
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Is quality of diet associated with the microvasculature? An analysis of diet quality and retinal vascular calibre in older adults.
Br. J. Nutr.
PUBLISHED: 03-26-2013
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It is unknown whether diet quality is associated with microvascular structure. The present study aimed to investigate the relationship between diet quality, reflecting adherence to dietary guidelines, with retinal microvascular calibre in older adults. The dietary data of 2720 Blue Mountains Eye Study participants, aged 50+ years, were collected using a semi-quantitative FFQ. A modified version of the Healthy Eating Index for Australians was developed to determine total diet scores (TDS). Fundus photographs were taken and retinal vascular calibre measured using computer-assisted techniques and summarised. After adjusting for age, sex, BMI, mean arterial blood pressure, smoking, serum glucose, leucocyte count and history of diagnosed stroke or CHD, persons with higher TDS had healthier retinal vessels cross-sectionally, with wider retinal arteriolar calibre (by approximately 3 ?m, comparing the highest with the lowest quartile of TDS, Ptrend = 0·0001) and narrower retinal venular calibre (by approximately 2·5 ?m; Ptrend = 0·02). In younger subjects aged ?65 years, increasing TDS (lowest to the highest quartile) was associated with healthier retinal vessels: approximately 4·4 ?m wider retinal arteriolar (Ptrend < 0·0001) and approximately 2·3 ?m narrower venular calibre (Ptrend = 0·03). After multivariable adjustment, however, baseline TDS were not associated with retinal arteriolar (Ptrend = 0·89) or venular calibre (Ptrend = 0·25), 5 years later. Also, baseline TDS were not associated with the 5-year change in retinal arteriolar (? = 0·14; P=0·29) or venular calibre (? = - 0·26; P=0·07). Greater compliance with published dietary guidelines (higher diet quality) was cross-sectionally associated with wider retinal arterioles and narrower venules, indicating better retinal microvascular health.
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Incidence and progression of geographic atrophy: observations from a population-based cohort.
Ophthalmology
PUBLISHED: 03-21-2013
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To examine early age-related macular degeneration (AMD) lesion characteristics and risk factors associated with the long-term development and progression of geographic atrophy (GA).
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Validity of a new optic disc grading software for use in clinical and epidemiological research.
Clin. Experiment. Ophthalmol.
PUBLISHED: 03-21-2013
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To determine the reliability and agreement of a new optic disc grading software program for use in clinical, epidemiological research.
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Medical characteristics of patients with macular telangiectasia type 2 (MacTel Type 2) MacTel project report no. 3.
Ophthalmic Epidemiol
PUBLISHED: 03-21-2013
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To determine whether the prevalences of various systemic conditions in participants of the MacTel Project Natural History Observation (NHO) Study differ from the corresponding prevalences in the general population.
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Incidence and progression of epiretinal membranes in eyes after cataract surgery.
Am. J. Ophthalmol.
PUBLISHED: 03-18-2013
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To assess eye-specific epiretinal membrane (ERM) incidence 3 years after phacoemulsification surgery, and ERM detection bias attributable to cataract.
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Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.
Ching-Yu Cheng, Maria Schache, M Kamran Ikram, Terri L Young, Jeremy A Guggenheim, Veronique Vitart, Stuart MacGregor, Virginie J M Verhoeven, Veluchamy A Barathi, Jiemin Liao, Pirro G Hysi, Joan E Bailey-Wilson, Beate St Pourcain, John P Kemp, George McMahon, Nicholas J Timpson, David M Evans, Grant W Montgomery, Aniket Mishra, Ya Xing Wang, Jie Jin Wang, Elena Rochtchina, Ozren Polašek, Alan F Wright, Najaf Amin, Elisabeth M van Leeuwen, James F Wilson, Craig E Pennell, Cornelia M van Duijn, Paulus T V M de Jong, Johannes R Vingerling, Xin Zhou, Peng Chen, Ruoying Li, Wan-Ting Tay, Yingfeng Zheng, Merwyn Chew, , Kathryn P Burdon, Jamie E Craig, Sudha K Iyengar, Robert P Igo, Jonathan H Lass, Emily Y Chew, Toomas Haller, Evelin Mihailov, Andres Metspalu, Juho Wedenoja, Claire L Simpson, Robert Wojciechowski, René Höhn, Alireza Mirshahi, Tanja Zeller, Norbert Pfeiffer, Karl J Lackner, Thomas Bettecken, Thomas Meitinger, Konrad Oexle, Mario Pirastu, Laura Portas, Abhishek Nag, Katie M Williams, Ekaterina Yonova-Doing, Ronald Klein, Barbara E Klein, S Mohsen Hosseini, Andrew D Paterson, Kari-Matti Mäkelä, Terho Lehtimäki, Mika Kähönen, Olli Raitakari, Nagahisa Yoshimura, Fumihiko Matsuda, Li Jia Chen, Chi Pui Pang, Shea Ping Yip, Maurice K H Yap, Akira Meguro, Nobuhisa Mizuki, Hidetoshi Inoko, Paul J Foster, Jing Hua Zhao, Eranga Vithana, E-Shyong Tai, Qiao Fan, Liang Xu, Harry Campbell, Brian Fleck, Igor Rudan, Tin Aung, Albert Hofman, André G Uitterlinden, Goran Bencic, Chiea-Chuen Khor, Hannah Forward, Olavi Pärssinen, Paul Mitchell, Fernando Rivadeneira, Alex W Hewitt, Cathy Williams, Ben A Oostra, Yik-Ying Teo, Christopher J Hammond, Dwight Stambolian, David A Mackey, Caroline C W Klaver, Tien-Yin Wong, Seang-Mei Saw, Paul N Baird.
Am. J. Hum. Genet.
PUBLISHED: 03-15-2013
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Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.
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Long-term changes in visual acuity in an older population over a 15-year period: the Blue Mountains Eye Study.
Ophthalmology
PUBLISHED: 03-01-2013
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To describe the change in visual acuity (VA) and incidence of visual impairment (VI) in an older population over a 15-year period.
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Correction of visual impairment by cataract surgery and improved survival in older persons: the Blue Mountains Eye Study cohort.
Ophthalmology
PUBLISHED: 01-10-2013
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We assessed whether correction of visual impairment (VI) by cataract surgery was associated with improved long-term survival in an older Australian population.
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Mutations in the EPHA2 gene are a major contributor to inherited cataracts in South-Eastern Australia.
PLoS ONE
PUBLISHED: 01-01-2013
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Congenital cataract is the most common cause of treatable visual impairment in children worldwide. Mutations in many different genes lead to congenital cataract. Recently, mutations in the receptor tyrosine kinase gene, EPHA2, have been found to cause congenital cataract in six different families. Although these findings have established EPHA2 as a causative gene, the total contribution of mutations in this gene to congenital cataract is unknown. In this study, for the first time, a population-based approach was used to investigate the frequency of disease causing mutations in the EPHA2 gene in inherited cataract cases in South-Eastern Australia. A cohort of 84 familial congenital or juvenile cataract index cases was screened for mutations in the EPHA2 gene by direct sequencing. Novel changes were assessed for segregation with the disease within the family and in unrelated controls. Microsatellite marker analysis was performed to establish any relationship between families carrying the same mutation. We report a novel congenital cataract causing mutation c.1751C>T in the EPHA2 gene and the previously reported splice mutation c.2826-9G>A in two new families. Additionally, we report a rare variant rs139787163 potentially associated with increased susceptibility to cataract. Thus mutations in EPHA2 account for 4.7% of inherited cataract cases in South-Eastern Australia. Interestingly, the identified rare variant provides a link between congenital and age-related cataract.
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Genetic loci for retinal arteriolar microcirculation.
PLoS ONE
PUBLISHED: 01-01-2013
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Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value?=?2.11×10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.
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Sifting the wheat from the chaff: prioritizing GWAS results by identifying consistency across analytical methods.
Genet. Epidemiol.
PUBLISHED: 11-30-2011
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The curse of multiple testing has led to the adoption of a stringent Bonferroni threshold for declaring genome-wide statistical significance for any one SNP as standard practice. Although justified in avoiding false positives, this conservative approach has the potential to miss true associations as most studies are drastically underpowered. As an alternative to increasing sample size, we compare results from a typical SNP-by-SNP analysis with three other methods that incorporate regional information in order to boost or dampen an otherwise noisy signal: the haplotype method (Schaid et al. [2002] Am J Hum Genet 70:425-434), the gene-based method (Liu et al. [2010] Am J Hum Genet 87:139-145), and a new method (interaction count) that uses genome-wide screening of pairwise SNP interactions. Using a modestly sized case-control study, we conduct a genome-wide association studies (GWAS) of age-related macular degeneration, and find striking agreement across all methods in regions of known associated variants. We also find strong evidence of novel associated variants in two regions (Chromosome 2p25 and Chromosome 10p15) in which the individual SNP P-values are only suggestive, but where there are very high levels of agreement between all methods. We propose that consistency between different analysis methods may be an alternative to increasingly larger sample sizes in sifting true signals from noise in GWAS.
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Retinal vessel caliber and myopic retinopathy: the blue mountains eye study.
Ophthalmic Epidemiol
PUBLISHED: 11-08-2011
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To evaluate changes in the retinal vasculature in eyes with myopic retinopathy.
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Is bilateral age-related macular degeneration less common in Asians than Caucasians?
Ophthalmic Epidemiol
PUBLISHED: 11-08-2011
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To compare the frequency and pattern of bilateral involvement of early and late age-related macular degeneration (AMD) between Asian Malays and Caucasians.
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The role of toll-like receptor variants in acute anterior uveitis.
Mol. Vis.
PUBLISHED: 10-14-2011
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Acute anterior uveitis (AAU) is the most common form of uveitis; however, while it is presumed to have an immunological basis, the precise underlying etiology remains elusive. Toll-like receptors (TLRs) have a key role in linking innate and adaptive immunity, thereby forming a molecular bridge between microbial triggers and the development of AAU. The purpose of this study was to investigate the role of TLR2 and TLR4 gene polymorphisms in the pathogenesis of AAU.
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Prevalence and characteristics of myopic retinopathy in a rural Chinese adult population: the Handan Eye Study.
Arch. Ophthalmol.
PUBLISHED: 09-14-2011
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To determine the prevalence, characteristics, and risk factors for myopic retinopathy in a rural population in Northern China.
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Cataract prevalence varies substantially with assessment systems: comparison of clinical and photographic grading in a population-based study.
Ophthalmic Epidemiol
PUBLISHED: 07-26-2011
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Cataract is the major cause of blindness worldwide yet there is no consensus on its assessment and definition. This study compares age-related cataract prevalence derived from two commonly used methods: clinical assessment using the Lens Opacity Classification System (LOCS III) and photographic grading using the Wisconsin Cataract Grading System (Wisconsin System).
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Parental history of hypertension is associated with narrower retinal arteriolar caliber in young girls.
Hypertension
PUBLISHED: 07-18-2011
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We aimed to assess the associations between parental history of hypertension and indicators of cardiovascular risk (retinal vessel diameter, presence of obesity, and elevated blood pressure) in prepubertal children. There were 1739 (77.7% of those eligible) 6-year-old students (863 girls and 876 boys) who were examined from a random cluster sample of 34 Sydney schools. Parents completed questionnaires about their medical conditions, including whether they have/had hypertension. Retinal images were taken with a digital fundus camera, and retinal vessel caliber was quantified using computer software. Anthropometric (height, weight, percentage of body fat, and body mass index) and blood pressure measures were collected. There were 160 children (9.2%) with a positive parental history of hypertension (either biological mother and/or father). Children with a positive versus negative parental history of hypertension had significantly higher body mass index (16.8 versus 16.5 kg/m(2); P=0.04) and systolic blood pressure (101.3 versus 99.8 mm Hg; P=0.01). Girls with positive versus negative parental history of hypertension had significantly higher diastolic blood pressure (?3.1 mm Hg; P=0.01) and narrower retinal arteriolar caliber (?4.3 ?m; P=0.0004). Positive parental history of hypertension was not associated with mean retinal vascular caliber among boys. We show that a positive parental history of hypertension in healthy prepubertal girls, but not boys, is associated with narrower retinal arteriolar vessels, likely conveying a predisposition to develop hypertension later in life. These findings may indicate the need for cardiovascular disease prevention measures starting early in life among offspring of hypertensive parents.
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Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.
Nat. Genet.
PUBLISHED: 05-27-2011
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Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.
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What is Visualize?

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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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.