Showing papers by "Ronald Klein published in 2010"
TL;DR: In this article, a meta-analysis of general population cohorts was conducted to assess the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality.
3,087 citations
TL;DR: In a nationally representative sample of US adults with diabetes aged 40 years and older, the prevalence of diabetic Retinopathy and vision-threatening diabetic retinopathy was high, especially among Non-Hispanic black individuals.
Abstract: Context The prevalence of diabetes in the United States has increased. People with diabetes are at risk for diabetic retinopathy. No recent national population-based estimate of the prevalence and severity of diabetic retinopathy exists. Objectives To describe the prevalence and risk factors of diabetic retinopathy among US adults with diabetes aged 40 years and older. Design, Setting, and Participants Analysis of a cross-sectional, nationally representative sample of the National Health and Nutrition Examination Survey 2005-2008 (N = 1006). Diabetes was defined as a self-report of a previous diagnosis of the disease (excluding gestational diabetes mellitus) or glycated hemoglobin A1c of 6.5% or greater. Two fundus photographs were taken of each eye with a digital nonmydriatic camera and were graded using the Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Study severity scale. Prevalence estimates were weighted to represent the civilian, noninstitutionalized US population aged 40 years and older. Main Outcome Measurements Diabetic retinopathy and vision-threatening diabetic retinopathy. Results The estimated prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was 28.5% (95% confidence interval [CI], 24.9%-32.5%) and 4.4% (95% CI, 3.5%-5.7%) among US adults with diabetes, respectively. Diabetic retinopathy was slightly more prevalent among men than women with diabetes (31.6%; 95% CI, 26.8%-36.8%; vs 25.7%; 95% CI, 21.7%-30.1%; P = .04). Non-Hispanic black individuals had a higher crude prevalence than non-Hispanic white individuals of diabetic retinopathy (38.8%; 95% CI, 31.9%-46.1%; vs 26.4%; 95% CI, 21.4%-32.2%; P = .01) and vision-threatening diabetic retinopathy (9.3%; 95% CI, 5.9%-14.4%; vs 3.2%; 95% CI, 2.0%-5.1%; P = .01). Male sex was independently associated with the presence of diabetic retinopathy (odds ratio [OR], 2.07; 95% CI, 1.39-3.10), as well as higher hemoglobin A1c level (OR, 1.45; 95% CI, 1.20-1.75), longer duration of diabetes (OR, 1.06 per year duration; 95% CI, 1.03-1.10), insulin use (OR, 3.23; 95% CI, 1.99-5.26), and higher systolic blood pressure (OR, 1.03 per mm Hg; 95% CI, 1.02-1.03). Conclusion In a nationally representative sample of US adults with diabetes aged 40 years and older, the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was high, especially among Non-Hispanic black individuals.
951 citations
University of Michigan1, University of Pennsylvania2, Mayo Clinic3, University of Pittsburgh4, University of Miami5, Johns Hopkins University6, Oregon Health & Science University7, National Institutes of Health8, Case Western Reserve University9, Vanderbilt University10, Duke University11, Thomas Jefferson University12, Cleveland Clinic13, United States Department of Veterans Affairs14, University of Wisconsin-Madison15, Kyoto University16, Harvard University17, Tufts University18, Boston University19, University of Santiago de Compostela20, University of California, Los Angeles21
TL;DR: A genome-wide association scan for age-related macular degeneration (AMD) showed that 329 of 331 individuals with the highest-risk genotypes were cases, and 85% of these had advanced AMD, consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis.
Abstract: We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10−75), ARMS2 (P < 10−59), C2/CFB (P < 10−20), C3 (P < 10−9), and CFI (P < 10−6). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10−11), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 × 10−7; CETP, P = 7.4 × 10−7) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL (P = 3.0 × 10−3) and ABCA1 (P = 5.6 × 10−4). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.
498 citations
TL;DR: It is suggested that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community.
Abstract: Objective: To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons. Methods: This is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002–2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions. Results: People with multiple (≥2) CMBs had lower Z scores on tests of processing speed (β-coefficient −0.16; 95% confidence interval −0.26 to −0.05) and executive function (−0.14; −0.24 to −0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (−0.25; −0.37 to −0.12), poorer executive function (−0.19; −0.31 to −0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62). Conclusion: Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community.
203 citations
TL;DR: Data show that the 25-year cumulative incidence of VI is related to modifiable risk factors and, therefore, that VI may be reduced by better glycemic and blood pressure control and avoidance of smoking.
171 citations
TL;DR: A narrower central retinal arteriole equivalent, wider centralretinal venule equivalent, focal arteriolar narrowing, and arteriovenous nicking were predictive of lacunar stroke.
Abstract: Background and Purpose— The retinal microvasculature reflects cumulative small-vessel damage from hypertension and other vascular processes. No study has prospectively examined retinal findings in relation to the incidence of clinical lacunar stroke in comparison with other ischemic stroke subtypes. Methods— In 10 496 adults initially free of stroke, we related retinal findings imaged during 1993 to 1995 with the incidence of hospitalized ischemic strokes through 2005. Results— During a median of 11.2 years of follow-up, 338 incident ischemic strokes occurred (66 lacunar, 192 nonlacunar thrombotic, and 80 cardioembolic). Generalized arteriolar narrowing as measured by the central retinal arteriole equivalent was associated with an increased incidence of lacunar stroke (multivariate-adjusted hazard ratio [HR] per 1-SD decrement of central retinal arteriole equivalent=1.67; 95% CI, 1.23–2.26) but was not associated with other ischemic stroke subtypes. Generalized venular widening as measured by the central ...
169 citations
TL;DR: Markers of socioeconomic status were associated with hearing impairment, suggesting that hearing impairment in older adults may be associated with modifiable lifestyle and environmental factors, and therefore, at least partially preventable.
162 citations
Erasmus University Rotterdam1, National University of Singapore2, University of Washington3, National Institutes of Health4, University of Melbourne5, University of Sydney6, University of Wisconsin-Madison7, Netherlands Institute for Neuroscience8, University of Amsterdam9, Johns Hopkins University10, National Yang-Ming University11, University of Iceland12, Group Health Cooperative13, Cedars-Sinai Medical Center14, Case Western Reserve University15, University of Western Australia16, QIMR Berghofer Medical Research Institute17, Duke University18, King's College London19, University of Newcastle20, University of Texas Health Science Center at Houston21, Singapore National Eye Center22
TL;DR: A population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease, and further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.
Abstract: There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10-8) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10-25, within the RASIP1 locus), rs225717 (6q24; p = 1.25×10-16, adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10-13, in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10-16, adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.
149 citations
TL;DR: Retinal microvascular abnormalities are associated with emergence of subclinical magnetic resonance imaging brain infarcts and white matter lesions, independent of shared risk factors.
Abstract: Silent brain infarct and white matter lesions are common radiological findings associated with the risk of clinical stroke and dementia; however, our understanding of their underlying pathophysiology and risk factors remains limited. This study aimed to determine whether assessment of retinal microvascular abnormalities could provide prognostic information regarding the risk of brain infarct and white matter lesions on magnetic resonance imaging. This study is based on a subset of 810 middle-aged persons without clinical stroke or baseline magnetic resonance imaging infarct enrolled in the Atherosclerosis Risk in Communities Brain Magnetic Resonance Imaging Study, a prospective, population-based study. Participants had a baseline magnetic resonance imaging brain examination and retinal photography in 1993–1995, and returned for a repeat magnetic resonance imaging examination in 2004–2006. Magnetic resonance images were graded for presence of any cerebral infarct, infarct with lacunar characteristics and white matter lesions according to standardized protocols. Retinal photographs were graded for presence of retinopathy lesions and retinal arteriolar abnormalities following a standardized protocol. Over a median follow-up of 10.5 years, 164 (20.2%) participants developed cerebral infarct, 131 (16.2%) developed lacunar infarct, 182 (24.2%) developed new white matter lesions and 49 (6.1%) had evidence of white matter lesion progression. After adjusting for age, gender, race, cardiovascular risk factors and carotid intima-media thickness, retinopathy was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval 1.42–5.60) and lacunar infarct (odds ratio 3.19; 95% confidence interval: 1.56–6.50). Retinal arteriovenous nicking was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval: 1.66–4.76), lacunar infarct (odds ratio 2.48; 95% confidence interval: 1.39–4.40) and white matter lesion incidence (odds ratio 2.12; 95% confidence interval: 1.18–3.81) and progression (odds ratio 2.22; 95% confidence interval: 1.00–5.88). In conclusion, retinal microvascular abnormalities are associated with emergence of subclinical magnetic resonance imaging brain infarcts and white matter lesions, independent of shared risk factors. Retinal vascular imaging may offer a non-invasive tool to investigate the pathogenesis and natural history of cerebral small-vessel disease.
131 citations
TL;DR: Well-imputed markers based on the HapMap III Mexican population identified 32 SNPs located in 11 chromosomal regions with nominal association with severe diabetic retinopathy at P-value less than .0001, which implicate genes involved in inflammation, oxidative stress and cell adhesion for the development and progression of diabetic Retinopathy.
Abstract: To identify genetic loci for severe diabetic retinopathy, 286 Mexican-Americans with type 2 diabetes from Starr County, Texas, completed physical examinations including fundus photography for diabetic retinopathy grading. Individuals with moderate-to-severe non-proliferative and proliferative diabetic retinopathy were defined as cases. Direct genotyping was performed using the Affymetrix GeneChip Human Mapping 100 K Set, and SNPs passing quality control criteria were used to impute markers available in HapMap Phase III Mexican population (MXL) in Los Angeles, California. Two directly genotyped markers were associated with severe diabetic retinopathy at a P-value less than .0001: SNP rs2300782 () mapped to an intron region of CAMK4 (calcium/calmodulin-dependent protein kinase IV) on chromosome 5, and SNP rs10519765 () on chromosomal 15q13 in the FMN1 (formin 1) gene. Using well-imputed markers based on the HapMap III Mexican population, we identified an additional 32 SNPs located in 11 chromosomal regions with nominal association with severe diabetic retinopathy at P-value less than .0001. None of these markers were located in traditional candidate genes for diabetic retinopathy or diabetes itself. However, these signals implicate genes involved in inflammation, oxidative stress and cell adhesion for the development and progression of diabetic retinopathy.
123 citations
TL;DR: The results suggest that 1) older adults may be retaining good hearing longer than previous generations and 2) modifiable factors contribute to hearing impairment in adults.
Abstract: There were significant changes in health and lifestyle throughout the 20th century which may have changed temporal patterns of hearing impairment in adults. In this study, the authors aimed to assess the effect of birth cohort on the prevalence of hearing impairment in an adult population aged 45–94 years, using data collected between 1993 and 2008 from 3 cycles of the Epidemiology of Hearing Loss Study (n ¼ 3,753; ages 48–92 years at baseline) and a sample of participants from the Beaver Dam Offspring Study (n ¼ 2,173; ages � 45 years). Hearing impairment was defined as a pure-tone average of thresholds at 0.5, 1, 2, and 4 kHz greater than 25-dB HL [hearing level]. Descriptive analysis, generalized additive models, and alternating logistic regression models were used to examine the birth cohort effect. Controlling for age, with every 5-year increase in birth year, the odds of having hearing impairment were 13% lower in men (odds ratio ¼ 0.87, 95% confidence interval: 0.83, 0.92) and 6% lower in women (odds ratio ¼ 0.94, 95% confidence interval: 0.89, 0.98). These results suggest that 1) older adults may be retaining good hearing longer than previous generations and 2) modifiable factors contribute to hearing impairment in adults. age groups; aging; cohort effect; hearing; hearing loss; logistic models; prevalence
TL;DR: It is shown that residing in locations with higher air pollution concentrations and experiencing daily increases in air pollution are associated with narrower retinal arteriolar diameters in older individuals, thus providing a link between air pollution and cardiovascular disease.
Abstract: Background: Long- and short-term exposures to air pollution, especially fine particulate matter (PM2.5), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature. Methods and Findings: Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000–2002). Long-term outdoor concentrations of PM2.5 were estimated at each participant’s home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM2.5. These relationships were observed in a joint exposure model with 20.8 mm (95% confidence interval [CI] 21.1 to 20.5) and 20.4 mm (95% CI 20.8 to 0.1) decreases in CRAE per interquartile increases in long- (3 mg/m 3 ) and short-term (9 mg/m 3 )P M2.5 levels, respectively. These reductions in CRAE are equivalent to 7- and 3year increases in age in the same cohort. Similarly, living near a major road was also associated with a 20.7 mm decrease (95% CI 21.4 to 0.1) in CRAE. Although the chronic association with CRAE was largely influenced by differences in exposure between cities, this relationship was generally robust to control for city-level covariates and no significant differences were observed between cities. Wider CRVE were associated with living in areas of higher PM2.5 concentrations, but these findings were less robust and not supported by the presence of consistent acute associations with PM2.5. Conclusions: Residing in regions with higher air pollution concentrations and experiencing daily increases in air pollution were each associated with narrower retinal arteriolar diameters in older individuals. These findings support the hypothesis that important vascular phenomena are associated with small increases in short-term or long-term air pollution exposures, even at current exposure levels, and further corroborate reported associations between air pollution and the development and exacerbation of clinical cardiovascular disease. Please see later in the article for the Editors’ Summary.
TL;DR: The risk of developing tinnitus was high for older adults, and associated with modifiable health and behavioral factors, and involved with discrete-time proportional hazards models.
Abstract: As part of a population-based study in Beaver Dam, Wisconsin, we estimated the 10-year cumulative incidence of tinnitus and its risk factors. Participants (n = 2922, aged 48-92 years) not reporting tinnitus at baseline (1993-1995) were followed for up to ten years. In addition to audiometric testing and anthropometric measures, data on tinnitus, health, and other history were obtained via questionnaire. Potential risk factors were assessed with discrete-time proportional hazards models. The 10-year cumulative incidence of tinnitus was 12.7%. The risk of developing tinnitus was significantly associated with: history of arthritis (hazard ratio (HR = 1.37), history of head injury (HR = 1.76), history of ever smoking (HR = 1.40), and among women, hearing loss (HR = 2.59). Alcohol consumption (HR = 0.63 for > or = 141 grams/week vs. <15 grams/week), age (among women, HR = 0.90 for each five-year increase in age), and among men, obesity (HR = 0.55), were associated with decreased risk. The risk of developing tinnitus was high for older adults, and associated with modifiable health and behavioral factors.
TL;DR: There was a lack of consensus on optimal glucose levels among physicians caring for individuals with diabetes and some clinicians believed that high blood glucose was less likely to result in the development of severe DR in subjects with type 2 diabetes than in those with type 1 diabetes.
Abstract: Diabetic retinopathy (DR) was the leading cause of severe visual impairment (VI) in subjects 25–64 years of age in the U.S. 30 to 40 years ago (1,2). At that time, severe VI (best corrected visual acuity of 20/200 or worse in the better eye) was 25 times as common in subjects with diabetes compared with those without diabetes. VI in subjects with diabetes resulted mainly from vitreous hemorrhage, tractional detachment of the macula due to proliferative diabetic retinopathy (PDR), and from macular edema involving the foveal area due to leakage from the breakdown of the blood-retinal barrier. Cataract and glaucoma also contributed to VI in individuals with diabetes.
Poor glycemic control was common in subjects with diabetes at that time (3,4). This was due, in part, to the fact that intensive appropriate insulin treatment was difficult to achieve. This was related to the technology that was available for monitoring glucose levels (self-monitoring of glycemic control was done by testing of spot urines; no glycosylated hemoglobin A1c was available) and to the way insulin was administered (no pump, treatment with one injection per day of a long-acting insulin). There was no definitive evidence that achieving good glycemic control would actually result in less DR; thus, there was a lack of consensus on optimal glucose levels among physicians caring for individuals with diabetes. Some clinicians believed that high blood glucose was less likely to result in the development of severe DR in subjects with type 2 diabetes than in those with type 1 diabetes (5). Blood pressure was also poorly controlled in individuals with diabetes at that time (3,4).
In 1972, the efficacy of photocoagulation had not yet been demonstrated to prevent visual loss due to PDR or macular edema. Vitrectomy, a surgical intervention to …
TL;DR: The prevalence of macular telangiectasia type 2 (0.1%) is higher than previously thought and is useful in estimating the burden of this condition in the population.
TL;DR: The 4-year incidence and progression of DR and the incidence of ME and CSME among Latinos are high compared to non-Hispanic whites and support the need to identify and modify risk factors associated with these long-term complications.
TL;DR: In this paper, the authors examined whether retinal microvascular assessment could provide predictive information on the risk of ventricular enlargement and sulcal widening on MRI and found that retinal enlargement is a risk factor for vascular dementia or Alzheimer disease.
Abstract: Background and Purpose— Cerebral atrophy, detected as ventricular enlargement or sulcal widening on MRI, is recognized as a risk factor for vascular dementia or Alzheimer disease. However, its underlying pathophysiology is not known. We examined whether retinal microvascular assessment could provide predictive information on the risk of ventricular enlargement and sulcal widening on MRI. Methods— A prospective, population-based study was conducted of 810 middle-aged persons without clinical stroke or MRI infarcts. All participants had a first cranial MRI and retinal photography in 1993 to 1995 and returned for a repeated MRI in 2004 to 2006 (median follow-up of 10.5 years). Retinal photographs were graded for presence of retinopathy and retinal microvascular abnormalities, and MRI images were graded for ventricular size and sulcal size according to standardized protocols. Ventricular enlargement and sulcal widening were defined as an increase in ventricular size or sulcal size of ≥3 of 10 grades between b...
TL;DR: People with wider retinal venules have reduced brachial FMD, independent of other vascular risk factors, which suggests that retina venular caliber, previously shown to predict stroke, may be a marker of underlying systemic endothelial dysfunction.
Abstract: Background and Purpose— Retinal vascular caliber changes have been shown to predict stroke, but the underlying mechanism of this association is unknown. We examined the relationship between retinal vascular caliber with brachial flow-mediated dilation (FMD), a measure of systemic endothelial function. Methods— The Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of persons 45 to 84 years of age residing in 6 US communities free of clinical cardiovascular disease at baseline. Brachial FMD data were collected at baseline (July 2000 to June 2002), and retinal vascular caliber was measured from digital retinal photographs at the second examination, immediately after the first (August 2002 to January 2004). Data were available for 2851 participants for analysis. Results— The mean brachial FMD was 4.39±2.79%. After adjusting for age and gender, brachial FMD was reduced in persons with wider retinal venular caliber (changes in FMD −0.25, 95% CI, −0.36, − 0.13; P<0.001, per SD increase in ...
TL;DR: A genome-wide association study in a series of families enriched for AMD was conducted and a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case–control cohort identified two novel genetic protective factors for AMD.
Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. We conducted a genome-wide association study in a series of families enriched for AMD and completed a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case-control cohort. We tested the top findings for replication in 1896 cases and 1866 controls and identified two novel genetic protective factors for AMD. In addition to the complement factor H (CFH) (P=2.3 × 10⁻⁶⁴) and age-related maculopathy susceptibility 2 (ARMS2) (P=1.2 × 10⁻⁶⁰) loci, we observed a protective effect at rs429608, an intronic SNP in SKIV2L (P=5.3 × 10⁻¹⁵), a gene near the complement component 2 (C2)/complement factor B (BF) locus, that indicates the protective effect may be mediated by variants other than the C2/BF variants previously studied. Haplotype analysis at this locus identified three protective haplotypes defined by the rs429608 protective allele. We also identified a new potentially protective effect at rs2679798 in MYRIP (P=2.9 × 10⁻⁴), a gene involved in retinal pigment epithelium melanosome trafficking. Interestingly, MYRIP was initially identified in the family-based scan and was confirmed in the case-control set. From these efforts, we report the identification of two novel protective factors for AMD and confirm the previously known associations at CFH, ARMS2 and C3.
TL;DR: The expression pattern encompassed the distribution of neuropathology of ALS, and could provide a rapid, relevant screening assay for TDP-43 variants and other disease-related proteins, as well as aiding studying diseases that affect both the spinal cord and brain.
TL;DR: In this article, the association between baseline retinal microaneurysm score and progression and regression of diabetic retinopathy, and response to treatment with candesartan in people with diabetes was studied.
Abstract: Diabet. Med. 28, 345–351 (2011)
Abstract
Objective To study the association between baseline retinal microaneurysm score and progression and regression of diabetic retinopathy, and response to treatment with candesartan in people with diabetes.
Methods This was a multicenter randomized clinical trial. The progression analysis included 893 patients with Type 1 diabetes and 526 patients with Type 2 diabetes with retinal microaneurysms only at baseline. For regression, 438 with Type 1 and 216 with Type 2 diabetes qualified. Microaneurysms were scored from yearly retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Retinopathy progression and regression was defined as two or more step change on the ETDRS scale from baseline. Patients were normoalbuminuric, and normotensive with Type 1 and Type 2 diabetes or treated hypertensive with Type 2 diabetes. They were randomized to treatment with candesartan 32 mg daily or placebo and followed for 4.6 years.
Results A higher microaneurysm score at baseline predicted an increased risk of retinopathy progression (HR per microaneurysm score 1.08, P < 0.0001 in Type 1 diabetes; HR 1.07, P = 0.0174 in Type 2 diabetes) and reduced the likelihood of regression (HR 0.79, P < 0.0001 in Type 1 diabetes; HR 0.85, P = 0.0009 in Type 2 diabetes), all adjusted for baseline variables and treatment. Candesartan reduced the risk of microaneurysm score progression.
Conclusions Microaneurysm counts are important prognostic indicators for worsening of retinopathy, thus microaneurysms are not benign. Treatment with renin-angiotensin system inhibitors is effective in the early stages and may improve mild diabetic retinopathy. Microaneurysm scores may be useful surrogate endpoints in clinical trials.
TL;DR: Overall, clinically inconsequential differences were observed between SEs before and after pharmacologic cycloplegia, suggesting that cyclopleGia may not be necessary in epidemiological studies of refraction in adults.
Abstract: Objective To compare refraction measured before and after pharmacologic cycloplegia. Methods This study used preliminary data from the Beaver Dam Offspring Study, which includes adult children of participants in the population-based Epidemiology of Hearing Loss Study of older adults living in Beaver Dam, Wisconsin. Data were available for 5018 eyes of 2529 participants. Refraction was defined by the spherical equivalent (SE), using autorefractor readings. Differences were calculated as the SE after drops were administered minus the SE before drops were administered. Myopia was defined as SE of −1 diopter (D) or less; emmetropia, as SE more than −1 D and less than 1 D; and hyperopia, as SE of 1 D or more. Results The mean age was 48 years (range, 22-84 years). The mean difference in SE between measurements before and after cycloplegia was 0.29 D (95% confidence interval, 0.28-0.31). The difference decreased with age and varied by refractive status for participants younger than 50 years, with the largest differences observed among young persons with hyperopic refractive errors. Across all age groups, agreement on classifications of refraction was high (84%-92%). Conclusions Overall, clinically inconsequential differences were observed between SEs before and after pharmacologic cycloplegia, suggesting that cycloplegia may not be necessary in epidemiological studies of refraction in adults.
TL;DR: Independently of other factors, baseline CRAE correlated with changes in glomerulopathy index, a composite measure of extracellular matrix accumulation in the mesangium and glomerular basement membrane, and a narrowing of the CRAE was related to mesangial matrix accumulation.
Abstract: We examined whether retinal vessel diameter in persons with type 1 diabetes mellitus is associated with changes in subclinical anatomical and functional indicators of diabetic nephropathy. Persons with type 1 diabetes mellitus had gradable fundus photographs and renal biopsy data at baseline and 5-year follow-up (n = 234). Retinal arteriolar and venular diameters were measured at baseline and follow-up. Central retinal arteriole equivalent (CRAE) and central retinal venule equivalent (CRVE) were computed. Baseline and 5-year follow-up renal structural variables were assessed by masked electron microscopic morphometric analyses from percutaneous renal biopsy specimens. Variables assessed included: mesangial fractional volume, glomerular basement membrane width, mesangial matrix fractional volume and glomerular basement membrane width composite glomerulopathy index. While controlling for other covariates, baseline CRAE was positively associated with change in the glomerulopathy index over the 5-year period. Change in CRAE was inversely related to a change in mesangial matrix fractional volume and abnormal mesangial matrix fractional volume, while change in CRVE was directly related to change in the volume fraction of cortex that was interstitium [Vv
(Int/cortex)] over the 5-year period. Baseline CRAE or CRVE or changes in these diameters were not related to changes in other anatomical or functional renal endpoints. Independently of other factors, baseline CRAE correlated with changes in glomerulopathy index, a composite measure of extracellular matrix accumulation in the mesangium and glomerular basement membrane. A narrowing of the CRAE was related to mesangial matrix accumulation. Changes in CRVE were related to changes in Vv
(Int/cortex), a measure of interstitial expansion in persons with type 1 diabetes mellitus.
TL;DR: Gene transfer efficiency was similar for both ages, but the tau vector caused more dopaminergic cell loss and a greater behavioral deficit in aged rats at specific doses and time points, validating the model for studies of age-related diseases.
TL;DR: Microcirculation (2010) 17, 381–393; doi: 10.1111/j.1549‐8719.2010.00033.x
Abstract: Objective: To examine the association between physical activity measured during leisure, sport, and work and retinal microvascular signs. Methods: Participants of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cross-sectional study, had retinal photographs taken at their third follow up visit (1993-1995). Retinal microvascular signs were assessed using a standardized protocol and retinal vascular caliber by a computer-assisted method. Leisure, sport, and work-related physical activity levels were determined through a modified Baecke physical activity questionnaire. Results: A higher level of physical activity during sport and work was significantly associated with a lower prevalence of arteriovenous (AV) nicking, wider venular caliber, and retinopathy. In multivariate models, persons with a level of sport-related physical activity above the median were less likely to have AV nicking (odds ratio [OR] = 0.87; 95% confidence interval [CI] 0.78-0.97) and wider retinal venules (OR = 0.91; 95% CI: 0.83-0.99). Persons with a level of work-related physical activity above the median were less likely to have diabetic retinopathy (OR = 0.66, 95% CI: 0.51-0.85). Conclusions: In this cross-sectional analyzes, higher levels of physical activity was associated with a lower prevalence of retinal microvascular abnormalities.
TL;DR: Data show 2 modifiable factors, uncontrolled hypertension and chronic kidney disease, are related to an increased incidence of retinopathy in nondiabetic persons and show that control of blood pressure is associated with a lower risk of incidentretinopathy compared with uncontrolled blood pressure.
Abstract: Objective To investigate the relationship of systemic factors to the 15-year cumulative incidence of retinopathy in nondiabetic persons in the Beaver Dam Eye Study. Methods Included were 4699 persons, 43 to 86 years of age at baseline examination in 1988-1990 and with follow-up in 1993-1995 and/or 1998-2000 and/or 2003-2005. Stereoscopic color fundus photographs were graded to determine the presence of retinopathy. The main outcome measure was cumulative incidence of retinopathy accounting for competing risk of death or diabetes mellitus. Results The 15-year cumulative incidence of retinopathy in the nondiabetic cohort was 14.2%. In multivariate analyses, older age (hazard ratio [HR] per age group, 1.13; 95% confidence interval [CI], 1.01-1.27), higher systolic blood pressure (HR per 10 mm Hg, 1.15; 95% CI, 1.07-1.20), presence of chronic kidney disease (HR, 1.51; 95% CI, 1.12-2.00), and wider retinal arteriolar diameter (HR per 10 μm, 1.17; 95% CI, 1.10-1.26) at baseline were associated with the incidence of retinopathy. In a separate model, the 15-year incidence of retinopathy was higher in those with uncontrolled hypertension compared with those who did not have hypertension (HR, 2.07; 95% CI, 1.51-2.83). There were no associations of body mass index, lipid levels, glycosylated hemoglobin level, smoking status, markers of inflammation, endothelial dysfunction and oxidative stress, and hematologic factors with retinopathy incidence. Conclusions These data show 2 modifiable factors, uncontrolled hypertension and chronic kidney disease, are related to an increased incidence of retinopathy in nondiabetic persons and show that control of blood pressure is associated with a lower risk of incident retinopathy compared with uncontrolled blood pressure.
TL;DR: Measures of SES at two points in the life-span were associated with subclinical atherosclerosis, and those in the lowest SES group had statistically larger age-sex-adjusted IMT thanThose in the highest SES groups.
TL;DR: In this paper, the association between ocular factors and age-related macular degeneration (AMD) in Latinos was assessed using a population-based, cross-sectional study of 6357 self-identified Latinos aged 40 years and older.
TL;DR: Age-specific incidence and progression of AMD in Latinos are lower than in non-Hispanic whites and while incident early AMD is more often unilateral, the risk of its development in the second eye is higher than in the first eye.
TL;DR: Obesity was associated with a higher risk of possible depression and had different influences on specific domains of depression symptoms measured by CES‐D Scale, suggesting the need for longitudinal studies on the effects of obesity on specific depression symptoms.
Abstract: Background: Depression and obesity are both important public health problems. However, it is not clear whether obesity contributes to depression. Our study aims to evaluate the association between obesity and possible depression. Methods: During the Beaver Dam Offspring Study examination, participants’ body weight and height were measured with a Detecto 758C digital scale with height bar, and depression symptoms were measured with the Center for Epidemiological Studies-Depression (CES-D) Scale. Other relevant information, such as demographic factors, lifestyle factors, comorbidities, and use of antidepressants, was also collected during the examination. There were 2,641 participants included in the analyses. Results: Obesity was associated with possible depression measured by CES-D Scale (OR 51.6, 95% CI: 1.3–2.0) after controlling for age and gender. The association remained similar after further adjustments. Obesity was significantly associated with all four domains measured by CES-D Scale after controlling for age and sex, with the largest effect on ‘‘Somatic Complaints’’ domain (b .15, 95% CI: 0.0836–0.223). The association with ‘‘Interpersonal Difficulties’’ was not significant after further adjustments. Conclusions: Obesity was associated with a higher risk of possible depression and had different influences on specific domains of depression symptoms measured by CES-D Scale. These findings suggest the need for longitudinal studies on the effects of obesity on specific depression symptoms. Depression and Anxiety 27:846–851, 2010. r 2010 Wiley-Liss, Inc.