Showing papers by "Ronald Klein published in 2012"

Global Prevalence and Major Risk Factors of Diabetic Retinopathy

Abstract: OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A 1c , and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.

Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

Abstract: Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.

Olfactory Impairment in an Adult Population: The Beaver Dam Offspring Study

Abstract: The objective of this study was to determine the prevalence of olfactory impairment and associated risk factors and the effects of olfactory impairment on dietary choices and quality of life. Odor identification was measured in 2838 participants aged 21-84 years (mean 49 years) in the Beaver Dam Offspring Study. The overall prevalence of olfactory impairment was 3.8%, increased with age (from 0.6% in those<35 years to 13.9% among those≥65 years) and was more common in men than women. In a multivariate model age (odds ratio [OR]=1.48, 95% confidence interval [CI]=1.33, 1.64 for every 5-year increase), nasal polyps or deviated septum (OR=2.69, 95% CI=1.62, 4.48), ankle-brachial index<0.9 (OR=3.62, 95% CI=1.45, 9.01), and smoking (women only) (OR=2.43, 95% CI=1.19, 4.98 ever smoked vs. never) were associated with an increased odds of olfactory impairment, whereas higher household income, ≥$50,000 versus <$50,000 per year, was associated with a decreased odds of olfactory impairment (OR=0.48, 95% CI=0.31, 0.73). Participants with olfactory impairment were less likely to report that food tasted as good as it used to, or that they experienced food flavors the same. There was no association between olfactory impairment and general health-related quality of life, depressive symptoms, or dietary choices. The prevalence of olfactory impairment was low in this largely middle-aged cohort, and some factors associated with olfactory impairment are potentially modifiable.

The advent of AAV9 expands applications for brain and spinal cord gene delivery.

Abstract: Introduction: Straightforward studies compared adeno-associated virus (AAV) serotypes to determine the most appropriate one for robust expression in the CNS. AAV9 was efficient when directly injected into the brain, but more surprisingly, AAV9 produced global expression in the brain and spinal cord after a peripheral, systemic route of administration to neonatal mice. Areas covered: Topics include AAV9 gene delivery from intraparenchymal, intravenous, intrathecal and intrauterine routes of administration, and related preclinical studies and disease models. Systemic AAV9 gene transfer yields remarkably consistent neuronal expression, though only in early development. AAV9 is versatile to study neuropathological proteins: microtubule-associated protein tau and transactive response DNA-binding protein 43 kDa (TDP-43). Expert opinion: AAV9 will be more widely used based on current data, although other natural serotypes and recombineered vectors may also support or improve upon wide-scale expression. A periphe...

Changes in retinal vessel diameter and incidence and progression of diabetic retinopathy.

Abstract: Results: During the first 4-year period, the mean change in CRAE and CRVE was �0.37 and 2.54 µm, respectively. The 6-year incidence and progression of DR and the incidence of PDR and ME from 1984-1986 to 19901992 were 56%, 39%, 15%, and 11%, respectively. In multivariate analyses, while controlling for duration, diabetes type, and other factors, an increase of 10 µm in CRVE from 1980-1982 to 1984-1986 was associated with increases in the 6-year incidence of DR (odds ratio [OR], 1.26; 95% CI, 1.10-1.43), progression of DR (OR, 1.21; 95% CI, 1.12-1.30), incidence of PDR (OR, 1.19; 95% CI, 1.07-1.32), and incidence of ME (OR, 1.16; 95% CI, 1.03-1.31). No interactions of these associations by diabetes type were found (data not shown). Change in CRAE was unrelated to the incidence or progression of DR (data not shown). Conclusions: Independent of DR severity level, glycemic control, and other factors, widening of the retinal venular but not arteriolar diameter was associated with subsequent incidence and progression of DR. The CRVE may provide additional information regarding the risk of incidence and progression of DR beyond traditional risk factors.

Retinal Microvascular Signs and Risk of Stroke: The Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract: Background and Purpose—Small-vessel disease contributes to the pathophysiology of stroke, and retinal microvascular signs have been linked to the risk of stroke. We examined the relationship of retinal signs with incident stroke in a multiethnic cohort. Methods—The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that enrolled participants without clinical cardiovascular diseases from 6 US communities between 2000 and 2002. Of the participants, 4849 (71.2%) had fundus photography performed in 2002 to 2004. Retinopathy and retinal vessel caliber were assessed from retinal images. Stroke risk factors including high-sensitivity C-reactive protein, carotid artery intima-media thickness, and coronary artery calcium were measured using standardized protocols. Incident stroke was confirmed from medical record review and death certificates. Results—After 6 years of follow-up, there were 62 incident strokes. Narrower retinal arteriolar caliber was associated with increased risk of stroke ...

Impaired glycemia and diabetic polyneuropathy: the OC IG Survey.

Abstract: OBJECTIVE To test whether diabetic polyneuropathies (DPNs), retinopathy, or nephropathy is more prevalent in subjects with impaired glycemia (IG) (abnormality of impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired HbA 1c [IA1C]) than in healthy subjects (non-IG). RESEARCH DESIGN AND METHODS Matched IG and non-IG volunteers were randomly identified from population-based diagnostic and laboratory registries, restudied, and reclassified as non-IG ( n = 150), IG ( n = 174), or new diabetes ( n = 218). RESULTS Frequency (%) of DPN in non-IG, IG, and new diabetes was 3 (2.0%), 3 (1.7%), and 17 (7.8%) narrowly defined (no other cause for polyneuropathy) and 19 (12.7%), 22 (12.6%), and 38 (17.4%) broadly defined. Mean and frequency distribution of composite scores of nerve conduction and quantitative sensation tests were not significantly different between IG and non-IG but were worse in new diabetes. Frequency of retinopathy and nephropathy was significantly increased only in new diabetes. In secondary analysis, small but significant increases in retinopathy and nephropathy were found in IGT, IFG, and IGT combined groups. CONCLUSIONS In population studies of Olmsted County, Minnesota, inhabitants, prevalence of typical DPN, retinopathy, and nephropathy was significantly increased only in subjects with new diabetes—not in subjects with IG as defined by American Diabetes Association (ADA) criteria of abnormality of IFG, IGT, or IA1C. For atypical DPN, such an increase was not observed even in subjects with new diabetes. In medical practice, explanations other than IG should be sought for patients with atypical DPN (chronic idiopathic axonal polyneuropathy) who have IG.

Signal quality assessment of retinal optical coherence tomography images.

Abstract: Purpose The purpose of this article was to assess signal quality of retinal optical coherence tomography (OCT) images from multiple devices using subjective and quantitative measurements. Methods A total of 120 multiframe OCT images from 4 spectral domain OCT devices (Cirrus, RTVue, Spectralis, and 3D OCT-1000) were evaluated subjectively by trained graders, and measured quantitatively using a derived parameter, maximum tissue contrast index (mTCI). An intensity histogram decomposition model was proposed to separate the foreground and background information of OCT images and to calculate the mTCI. The mTCI results were compared with the manufacturer signal index (MSI) provided by the respective devices, and to the subjective grading scores (SGS). Results Statistically significant correlations were observed between the paired methods (i.e., SGS and MSI, SGS and mTCI, and mTCI and MSI). Fisher's Z transformation indicated the Pearson correlation coefficient ρ ≥ 0.8 for all devices. Using the Deming regression, correlation parameters between the paired methods were established. This allowed conversion from the proprietary MSI values to SGS and mTCI that are universally applied to each device. Conclusions The study suggests signal quality of retinal OCT images can be evaluated subjectively and objectively, independent of the devices. Together with the proposed histogram decomposition model, mTCI may be used as a standardization metric for OCT signal quality that would affect measurements.

A spirulina-enhanced diet provides neuroprotection in an α-synuclein model of Parkinson's disease

Abstract: Inflammation in the brain plays a major role in neurodegenerative diseases. In particular, microglial cell activation is believed to be associated with the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). An increase in microglia activation has been shown in the substantia nigra pars compacta (SNpc) of PD models when there has been a decrease in tyrosine hydroxylase (TH) positive cells. This may be a sign of neurotoxicity due to prolonged activation of microglia in both early and late stages of disease progression. Natural products, such as spirulina, derived from blue green algae, are believed to help reverse this effect due to its anti-inflammatory/anti-oxidant properties. An adeno-associated virus vector (AAV9) for α-synuclein was injected in the substantia nigra of rats to model Parkinson's disease and to study the effects of spirulina on the inflammatory response. One month prior to surgeries, rats were fed either a diet enhanced with spirulina or a control diet. Immunohistochemistry was analyzed with unbiased stereological methods to quantify lesion size and microglial activation. As hypothesized, spirulina was neuroprotective in this α-synuclein model of PD as more TH+ and NeuN+ cells were observed; spirulina concomitantly decreased the numbers of activated microglial cells as determined by MHCII expression. This decrease in microglia activation may have been due, in part, to the effect of spirulina to increase expression of the fractalkine receptor (CX3CR1) on microglia. With this study we hypothesize that α-synuclein neurotoxicity is mediated, at least in part, via an interaction with microglia. We observed a decrease in activated microglia in the rats that received a spirulina- enhanced diet concomitant to neuroprotection. The increase in CX3CR1 in the groups that received spirulina, suggests a potential mechanism of action.

Diabetic retinopathy in the SEARCH for Diabetes in Youth Cohort: a pilot study.

Abstract: Diabet. Med. 29, 1148–1152 (2012) Abstract Aims The aim of this pilot study was to generate an initial estimate of the prevalence and correlates of diabetic retinopathy in a racially and ethnically diverse sample of youth with Type 1 and Type 2 diabetes mellitus. Methods A pilot study was conducted among 222 individuals with Type 1 diabetes (79% non-Hispanic white, 21% other) and 43 with Type 2 diabetes (28% non-Hispanic white, 72% other), all of > 5 years duration (mean duration 6.8 years) who participated in the SEARCH for Diabetes in Youth study. Diabetic retinopathy was assessed using non-mydriatic retinal photography of both eyes. Results The prevalence of diabetic retinopathy was 17% for Type 1 diabetes and 42% for Type 2 diabetes (odds ratio 1.50, 95% CI 0.58–3.88; P = 0.40 adjusted for age, duration, gender, race/ethnicity, parental education and HbA1c. HbA1c was significantly higher among those with any diabetic retinopathy (adjusted mean 79 mmol/mol, 9.4%) vs. no diabetic retinopathy (adjusted mean 70 mmol/mol, 8.6%) (P = 0.015). LDL cholesterol was also significantly higher among those with any diabetic retinopathy (adjusted mean 107.2 mg/dl) compared with those without diabetic retinopathy (adjusted mean 97.9 mg/dl) (P = 0.04). Conclusions The prevalence of diabetic retinopathy in contemporary young individuals was substantial, particularly among minority youth and those with Type 2 diabetes. Further long-term study of diabetic retinopathy in youth is needed.

The Association of Systemic Microvascular Changes with Lung Function and Lung Density: A Cross-Sectional Study

Abstract: Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45-84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA) were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV(1)) (P<0.001) and FEV(1)/forced vital capacity (FVC) ratio (P = 0.04). Albumin-to-creatinine ratio was inversely associated with FEV(1) (P = 0.002) but not FEV(1)/FVC. Myocardial blood flow (n = 126) was associated with lower FEV(1) (P = 0.02), lower FEV(1)/FVC (P = 0.001) and greater percentage LAA (P = 0.04). Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.

Long-term use of aspirin and age-related macular degeneration.

Abstract: Context Aspirin is widely used for relief of pain and for cardioprotective effects. Its use is of concern to ophthalmologists when ocular surgery is being considered and also in the presence of age-related macular degeneration (AMD). Objective To examine the association of regular aspirin use with incidence of AMD. Design, Setting, and Participants The Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in Wisconsin. Examinations were performed every 5 years over a 20-year period (1988-1990 through 2008-2010). Study participants (N = 4926) were aged 43 to 86 years at the baseline examination. At subsequent examinations, participants were asked if they had regularly used aspirin at least twice a week for more than 3 months. Main Outcome Measure Incidence of early AMD, late AMD, and 2 subtypes of late AMD (neovascular AMD and pure geographic atrophy), assessed in retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. Results The mean duration of follow-up was 14.8 years. There were 512 incident cases of early AMD (of 6243 person-visits at risk) and 117 incident cases of late AMD (of 8621 person-visits at risk) over the course of the study. Regular aspirin use 10 years prior to retinal examination was associated with late AMD (hazard ratio [HR], 1.63 [95% CI, 1.01-2.63]; P = .05), with estimated incidence of 1.76% (95% CI, 1.17%-2.64%) in regular users and 1.03% (95% CI, 0.70%-1.51%) in nonusers. For subtypes of late AMD, regular aspirin use 10 years prior to retinal examination was significantly associated with neovascular AMD (HR, 2.20 [95% CI, 1.20-4.15]; P = .01) but not pure geographic atrophy (HR, 0.66 [95% CI, 0.25-1.95]; P = .45). Aspirin use 5 years (HR, 0.86 [95% CI, 0.71-1.05]; P = .13) or 10 years (HR, 0.86 [95% CI, 0.65-1.13]; P = .28) prior to retinal examination was not associated with incident early AMD. Conclusions Among an adult cohort, aspirin use 5 years prior to observed incidence was not associated with incident early or late AMD. However, regular aspirin use 10 years prior was associated with a small but statistically significant increase in the risk of incident late and neovascular AMD.

Generational differences in the reporting of tinnitus.

Abstract: Objectives—Recent research suggests that hearing impairment is declining among older adults compared to earlier generations of the same age. Tinnitus is often associated with hearing impairment, so one might hypothesize that the prevalence of tinnitus is declining in a similar manner. The purpose of this study was to utilize multi-generational data with repeated measures to determine if the prevalence of tinnitus is declining among more recent generations.

Age-Related Macular Degeneration and Long-Term Risk of Stroke Subtypes

Abstract: Background and Purpose—We examined the relationship of age-related macular degeneration (AMD) with incident stroke, including stroke subtypes of cerebral infarction and intracerebral hemorrhage. Methods—We included 12 216 participants with retinal photographs taken at the third examination visit (1993–1995) from the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cohort study in middle-aged persons. Images were evaluated for AMD signs according to a standardized protocol. Incident events of stroke and its subtypes were identified and validated through case record review over time. Results—AMD was diagnosed in 591 participants, of whom 576 had early and 15 late AMD. After a mean follow-up of 13.0 years (SD, 3.3), 619 persons developed an incident stroke, including 548 cerebral infarction and 57 intracerebral hemorrhages. Participants with any AMD were at an increased risk of stroke (multivariable adjusted hazard ratio, 1.51; 95% CI, 1.11–2.06) with a stronger association for intracereb...

Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility--Reykjavik Study (AGES-R).

Abstract: Aims/hypothesis We aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus.

Replication Analysis for Severe Diabetic Retinopathy

Abstract: PURPOSE The purpose of this study is to attempt to replicate the top single nucleotide polymorphism (SNP) associations from a previous genome-wide association study (GWAS) for the sight-threatening complications of diabetic retinopathy in an independent cohort of diabetic subjects from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). METHODS This study included 469 type 1 diabetic, Caucasian subjects from WESDR. Cases (n = 208) were defined by prior laser treatment for either proliferative diabetic retinopathy or diabetic macular edema. Controls (n = 261) were all other subjects in the cohort. Three hundred eighty-nine SNPs were tested for association using the Illumina GoldenGate custom array. A retinopathy-only subanalysis was conducted in 437 subjects by removing those with end-stage renal disease. Evaluation for association between cases and controls was conducted by using chi-square tests. A combined analysis incorporated the results from WESDR with the prior GWAS. RESULTS No associations were significant at a genome-wide level. The analysis did identify SNPs that can be pursued in future replication studies. The top association was at rs4865047, an intronic SNP, in the gene CEP135 (P value 2.06 × 10(-5)). The top association from the subanalysis was at rs1902491 (P value 2.81 × 10(-5)), a SNP that sits upstream of the gene NPY2R. CONCLUSIONS This study nominates several novel genetic loci that may be associated with severe diabetic retinopathy. In order to confirm these findings, replication and extension in additional cohorts will be necessary as susceptibility alleles for diabetic retinopathy appear to be of modest effect.

Effect of the Y402H Variant in the Complement Factor H Gene on the Incidence and Progression of Age-Related Macular Degeneration: Results From Multistate Models Applied to the Beaver Dam Eye Study

Abstract: Information regarding the development and progression of age-related macular degeneration (AMD) has emerged from clinical and epidemiological studies.1–11 This has resulted in the development of severity scales ranging from no lesions through the most severe lesions (neovascular AMD and/or geographic atrophy).6,12–14 Most scales use size, type and area of drusen and retinal pigment epithelium (RPE) pigmentary abnormalities to define intermediate severity levels. While most epidemiological studies have investigated incidence and progression of AMD, few studies have examined regression and associated protective factors.2,5,9,11 In the Chesapeake Bay Waterman Study, large soft drusen disappeared in 34% of eyes over a 5-year follow-up.2 In the Melton Mowbray study, 20% of soft drusen regressed over a 7-year period.9 It is unclear what factors are associated with regression or how AMD transitions through various stages. Previous studies show that the Y402H polymorphism in the Complement Factor H (CFH) gene on chromosome 1q is strongly associated with AMD,15–18 suggesting a role for innate immunity and inflammation in AMD pathogenesis. Most studies have examined relationships of the Y402H polymorphism to incidence of early or progression to late AMD but few have considered progression through various stages of AMD or regression of AMD.19–22 Multi-state models (MSMs) can be used to gain greater insight into this relationship. We use MSMs to model transitions from the state at a study visit to the state at a subsequent visit.23–27 In practice, disease states are observed at intermittent study visits, and exact transition times are not observed; even when the exact date of death is known, the AMD state at death is unknown.28–31 Additionally, observations are frequently censored. For example, at the end of follow-up, subjects are known to be alive but their AMD state at that time is unknown. In this paper, we use MSMs to examine the effects of age, sex and the Y402H variant in the CFH gene on incidence, progression and regression of AMD as well as mortality in the population-based Beaver Dam Eye Study (BDES).

Using distance correlation and SS-ANOVA to assess associations of familial relationships, lifestyle factors, diseases, and mortality

Abstract: We present a method for examining mortality as it is seen to run in families, and lifestyle factors that are also seen to run in families, in a subpopulation of the Beaver Dam Eye Study. We observe that pairwise distance between death age in related persons is on average less than pairwise distance in death age between random pairs of unrelated persons. Our goal is to examine the hypothesis that pairwise differences in lifestyle factors correlate with the observed pairwise differences in death age that run in families. Szekely and Rizzo [Szekely GJ, Rizzo ML (2009) Ann Appl Stat 3(4): 1236–1265] have recently developed a method called distance correlation, which is suitable for this task with some enhancements. We build a Smoothing Spline ANOVA (SS-ANOVA) model for predicting death age based on four major lifestyle factors generally known to be related to mortality and four major diseases contributing to mortality, to develop a lifestyle mortality risk vector and a disease mortality risk vector. We then examine to what extent pairwise differences in these scores correlate with pairwise differences in mortality as they occur between family members and between unrelated persons. We find significant distance correlations between death ages, lifestyle factors, and family relationships. Considering only sib pairs compared with unrelated persons, distance correlation between siblings and mortality is, not surprisingly, stronger than that between more distantly related family members and mortality. The methodological approach here adapts to exploring relationships between multiple clusters of variables with observable (real-valued) attributes, and other factors for which only possibly nonmetric pairwise dissimilarities are observed.

Relationship of Blood Pressure and Other Factors to Serial Retinal Arteriolar Diameter Measurements Over Time: The Beaver Dam Eye Study

Abstract: Objective To describe the relationship of blood pressure (BP), antihypertensive medication use, and other factors to serial measurements of retinal arteriolar diameters over time in the Beaver Dam Eye Study. Methods Retinal arteriolar diameter was measured by computer-assisted methods and summarized as central retinal arteriolar equivalent (CRAE) in 4573 persons aged 43 to 99 years at 4 examinations (each separated by 5 years) during a 15-year period. Associations of CRAE with risk factors measured concurrently and 5 years previously were determined using multivariate analyses. Results While adjusting for image quality, refraction, and lens status, age (per 10 years: β estimate, −0.73; P Conclusions Retinal arteriolar diameter is independently associated with past and current systolic BP, calcium channel blocker use, smoking status, body mass index, and heavy drinking during 5-year intervals. The relationships with CRAE are stronger for concurrent than for past measures of these variables.

Relationship of Retinal Vessel Caliber to Cardiovascular Disease and Mortality in African Americans With Type 1 Diabetes Mellitus

Abstract: Objective To examine the relationship between retinal arteriolar and venular diameter and the 6-year incidence of cardiovascular disease and mortality among African Americans with type 1 diabetes mellitus. Methods Included were 468 African Americans with type 1 diabetes mellitus who participated in the New Jersey 725 and who had undergone a 6-year follow-up examination. At both baseline and 6-year follow-up, hypertension and presence of heart disease, stroke, or lower extremity arterial disease (LEAD) were documented and confirmed by review of hospital admission and medical records. Computer-assisted grading from digitized images of retinal photographs was accomplished to determine the average diameter of retinal arterioles (central retinal arteriolar equivalent) and venules (central retinal venular equivalent). Retinal vessel diameter size was examined in relation to the 6-year incidence of hypertension, any cardiovascular disease (heart disease, stroke, or LEAD), heart disease or stroke, LEAD, and mortality. Results Narrower central retinal arteriolar equivalent at baseline significantly and independently predicted 6-year incidence of any cardiovascular disease and LEAD, whereas larger retinal venular diameter at baseline significantly and independently predicted 6-year incidence of hypertension. Proteinuria and retinopathy severity at baseline were stronger predictors of mortality than retinal vascular diameter. Conclusion In African Americans with type 1 diabetes mellitus, baseline retinal vessel caliber is an independent predictor of incident hypertension and LEAD.

Alcohol consumption, drinking pattern, and self-reported visual impairment.

Abstract: Purpose: To examine whether alcohol drinking status and drinking pattern are associated with self-reported visual impairment.Methods: We used data from the Behavioral Risk Factor Surveillance System, a state-based telephone health survey conducted by random-digit dialing among non-institutionalized US adults. The Visual Impairment and Access to Eye Care module was implemented among 42, 713 adults aged 50 years and older in 2005 and 2006. Visual impairment was defined as any degree of difficulty experienced in recognizing a friend across the street or reading print in newspaper, magazine, recipe, menu, or numbers on the telephone with usual correction. Drinking patterns included drinking quantity (drinks per drinking day), frequency (drinking days in the past month), and binge drinking.Results: After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, Body Mass Index, history of cardiovascular diseases, diabetes, and eye diseases, current drinking status was not associated with...

Relationship between retinopathy severity, visual impairment and depression in persons with long-term type 1 diabetes

Abstract: Purpose: Our aim was to investigate the proportion of individuals with depression and its association with diabetic retinopathy and visual impairment in a cohort with 25 or more years of type 1 diabetes.Methods: This was a cross-sectional analysis at the 25-year follow-up of the population-based cohort of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Examinations followed standardized protocols and included clinical and ophthalmic evaluations and questionnaires to assess current and past medical history, use of medications, and cigarette smoking. The Center for Epidemiologic Studies Depression Scale (CES-D) was administered to all participants. Depression was defined as use of antidepressant or CES-D score ≥16.Results: A total of 484 individuals were included in the analysis. The proportion of depression was 37.8% (95% confidence interval 33.4-42.3%). A higher proportion of individuals with depression was observed among those with more severe diabetic retinopathy and visual impairment. Howeve...