Beaver Dam Eye Study Research Articles

Determinants of Retinal Venular Diameter: The Beaver Dam Eye Study

To describe how retinal venular diameter changes over time for an individual and to examine differences in these changes among people with different risk profiles. Population-based cohort study. A total of 4600 persons aged 43 to 86 years from the Beaver Dam Eye Study (BDES) who participated in at least 1 examination and had venular diameter measured in the right eye. Data from 4 examinations during a 15-year period were analyzed. Retinal venular diameter was measured from photographs at each examination by computer-assisted methods and summarized as the central retinal venular equivalent (CRVE). Associations of risk factors with concurrent CRVE measurements and changes in CRVE over time were determined using multivariate analyses. Central retinal venular equivalent. The CRVE tended to narrow with age. Mean CRVE was approximately 5 μm smaller (225 vs. 230 μm) for the average 70-year-old compared with the average 50-year-old, and was approximately 13 μm smaller (217 vs. 230 μm) for the average 85-year-old compared with the average 50-year-old. Male sex (beta estimate [β] = 5.24; 95% confidence interval [CI], 3.58-6.90), history of current cigarette smoking (β = 9.38; 95% CI, 8.26-10.49), and higher white blood cell (WBC) count (per 1000/μL: β = 0.95; 95% CI, 0.74-1.16) were independently associated with larger concurrent CRVE, whereas higher mean arterial blood pressure (per 5 mmHg: β = -0.36; 95% CI, -0.50 to -0.23) and higher serum high-density lipoprotein (HDL) cholesterol (per 10 mg/dl: β = 0.89; 95% CI, -1.15 to -0.63) were independently associated with smaller concurrent CRVE. History of cardiovascular disease (CVD) (β = -0.16; 95% CI, -0.26 to -0.06) and presence of chronic kidney disease (CKD) (β = -0.20; 95% CI, -0.34 to -0.05) were associated with a greater decrease in CRVE over time. These data show that retinal venular diameter tends to narrow with age; concurrent venular diameter is independently associated with sex, blood pressure, serum HDL cholesterol, WBC count, and history of current cigarette smoking; and change in CRVE is independently associated with a history of CVD and presence of CKD. The different independent effects of these interrelated factors on CRVE highlight the complex relationship between CRVE and systemic diseases and conditions and the difficulty in determining specific causes of change in CRVE over time. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Relationship of Cataract and Cataract Extraction to Age-related Macular Degeneration: The Beaver Dam Eye Study

To examine the associations of cataract and cataract surgery with early and late age-related macular degeneration (AMD) over a 20-year interval. Longitudinal population-based study of age-related eye diseases. Beaver Dam Eye Study participants. Persons aged 43 to 86 years participated in the baseline examination in 1988-1990. Participants were followed up at 5-year intervals after the baseline examination. Examinations consisted of ocular examination with lens and fundus photography, medical history, measurements of blood pressure, height, and weight. Values of risk variables were updated, and incidences of early and late AMD were calculated for each 5-year interval. Odds ratios were computed using discrete linear logistic regression modeling with generalized estimating equation methods to account for correlation between the eyes and multiple intervals. Age-related macular degeneration. After adjusting for age and sex, neither cataract nor cataract surgery was associated with increased odds for developing early AMD. Further adjusting for high-risk gene alleles (CFH and ARMS2) and other possible risk factors did not materially affect the odds ratio (OR). However, cataract surgery was associated with incidence of late AMD (OR 1.93; 95% confidence interval [CI], 1.28-2.90). This OR was not materially altered by further adjusting for high-risk alleles (CFH Y402H, ARMS2) or other risk factors. The OR for late AMD was higher for cataract surgery performed 5 or more years prior compared with less than 5 years prior. These data strongly support the past findings of an association of cataract surgery with late AMD independent of other risk factors, including high-risk genetic status, and suggest the importance of considering these findings when counseling patients regarding cataract surgery. These findings should provide further impetus for the search for measures to prevent or delay the development of age-related cataract.

Association of oxidative stress with mortality: the Beaver Dam Eye Study.

Epidemiological studies have shown that oxidative stress is associated with cardiovascular disease (CVD) and diabetes. However, the association of oxidative stress marker with non-CVD and CVD mortality has not been extensively evaluated. The association of baseline serum 8-isoprostane (8-ISO) with all-cause, non-CVD, and CVD mortality was examined in a random subset (n = 1,753) of a population-based study of 4,926 adults (99% non-Hispanic whites; 56% women) aged 43-86 years from the Beaver Dam Eye Study. Cause of death was ascertained by death certificate between 1987 and 2002. 8-ISO was measured by immunoassay. Cox proportional hazards regression analysis was used to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs) by one 8-ISO standard deviation. During a median follow-up of 13.1 years, 590 (33.7%) participants died (290 CVD deaths). After adjusting for socio-demographics and CVD risk factors, 8-ISO was significantly associated with all-cause (HR = 1.1, 95% CI 1.01-1.2) and non-CVD (HR = 1.14, 95% CI 1.01-1.28) mortality but not with CVD mortality (HR = 1.06, 95% CI 0.93-1.2). When limited to participants with BMI < 25 kg/m2, individuals in the highest 8-ISO quartile had approximately 34 to 36% increased risk of all-cause, non-CVD, and CVD death compared to those at the lowest quartile. In contrast, 8-ISO was not significantly associated with mortality among those with BMI ≥ 25 kg/m2. These findings suggest that baseline serum 8-ISO, a marker of oxidative stress, is an independent risk factor of all-cause, non-CVD, and CVD mortality among a cohort of middle-aged adults with normal BMI.

Association of biomarkers for inflammation, endothelial dysfunction and oxidative stress with cognitive impairment: the Epidemiology of Hearing Loss Study

Individual biomarkers of inflammation, endothelial dysfunction and oxidative stress have been associated with cognitive impairment. This study explored whether a combination of biomarkers could prospectively identify those who developed cognitive decline. Biomarkers were obtained during the baseline examination of the Beaver Dam Eye Study (1988-90), and cognitive status was assessed during the 5-year follow-up examination of the Epidemiology of Hearing Loss Study (1998-2000). Cognitive impairment was defined as a score of < 24 points on the Mini-Mental State Examination or self- or proxy report of Alzheimer Disease or dementia. Among those with cognitive data, interleukin-6, isoprostanes, protein carbonyl, soluble inter-cellular adhesion molecule-1 and vascular cell adhesion molecule-1 were available for 950 participants and 2,336 had high sensitivity C-reactive protein. Biomarkers of inflammation and endothelial dysfunction were not associated with cognitive impairment. There was a weak inverse association between higher levels of protein carbonyl content and cognitive impairment (OR, 0.8 per quartile of protein carbonyl content, p=0.045 unadjusted for multiple comparisons). This was not significant on multiple testing and may have been a chance finding. We found that many markers of inflammation and endothelial dysfunction were not associated with cognitive impairment. An inverse association with carbonyl protein, a marker of oxidative stress needs further confirmation.

Modifiable determinants of hearing impairment in adults

ObjectiveTo identify factors contributing to the declining prevalence of hearing impairment in more recent generations. MethodsWe used data on hearing thresholds and potential risk factors of hearing impairment collected from studies in Beaver Dam, Wisconsin, the Epidemiology of Hearing Loss Study (1993–1995, n=3753; 1998–2000, n=2800 and 2003–2005, n=2395), the concurrent Beaver Dam Eye Study on the same cohort, and a subgroup (n=2173) of the Beaver Dam Offspring Study (2005–2008). ResultsEducational attainment significantly reduced the odds ratio (OR) of the birth cohort effect on hearing impairment from 0.90 to 0.93, while a history of ear infection had a reverse effect on the decreasing trend (significantly changing the OR from 0.93 to 0.94). Occupational noise exposure, smoking, and a history of cardiovascular disease, while associated with hearing impairment, did not attenuate the cohort effect. The cohort effect remained significant after known risk factors were adjusted (OR=0.93; 95% confidence interval, 0.89–0.97). ConclusionThese data provide strong evidence that environmental, lifestyle, or other modifiable factors contribute to the etiology of hearing impairment and add support to the idea that hearing impairment in adults may be prevented or delayed.

Linkage analysis of quantitative refraction and refractive errors in the Beaver Dam Eye Study.

Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10(-4)), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10(-3) and 1.48 × 10(-3), respectively) and to 7p15 of refraction (empiric P = 9.43 × 10(-4)). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10(-3)), a region previously linked to high myopia. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11.

Complete Blood Cell Count and Retinal Vessel Diameters

To examine the cross-sectional associations of components of the complete blood cell count with retinal vessel diameters. The data are from the baseline examination of the Beaver Dam Eye Study cohort (n=4730) from March 1, 1988, to September 14, 1990. Blood pressure was measured, a medical history including questions on cigarette smoking was obtained, and fundus photographs centered on the optic disc were taken and digitized. Retinal arteriole and venule diameters were measured using computer-assisted software. The central retinal arteriole equivalent and central retinal venule equivalent were computed. A complete blood cell count was done. In age- and sex-adjusted analyses, red blood cell count, hemoglobin level, hematocrit, and white blood cell count were all statistically significantly associated with central retinal venule equivalent and central retinal arteriole equivalent, while platelet count was associated only with central retinal venule equivalent. These relationships persisted in more fully adjusted models, except platelet count became statistically significantly associated with both central retinal arteriole equivalent and central retinal venule equivalent. Blood components as measured in a complete blood cell count are significant correlates of retinal vessel diameters and should be considered in analyses where retinal blood vessel diameters are outcomes.

Serum cystatin C and the incidence of type 2 diabetes mellitus

To examine the association of serum cystatin C with the incidence of type 2 diabetes mellitus over a 15 year follow-up period. The 15 year cumulative incidence of diabetes was measured in a cohort of Beaver Dam Eye Study participants (n = 3,472, 1988-2003). A person was defined as developing diabetes (a positive history of diabetes mellitus treated with insulin, oral hypoglycaemic agents and/or diet, or elevations in glycosylated haemoglobin levels) in the absence of diabetes at baseline. The relation of cystatin C and other risk factors to incident type 2 diabetes was determined using discrete time extension of the proportional hazards model. The 15 year cumulative incidence of diabetes was estimated to be 9.6%. After controlling for age, sex, body mass index, smoking status, glycosylated haemoglobin, proteinuria, chronic kidney disease status and hypertension status, serum cystatin C at baseline was associated with the 15 year cumulative incidence of type 2 diabetes (OR per log of cystatin C unit 2.19, 95% CI 1.02-4.68). These findings show a positive relationship of serum cystatin C levels with the incidence of type 2 diabetes mellitus independently of confounding risk factors. The findings strongly suggest the need for further evaluation of the potential importance of cystatin C in the pathogenesis of type 2 diabetes mellitus.

Heritability of optic disc diameters: a twin study

To assess the relative influence of genetic and environmental factors on optic disc size and cup/disc ratio in healthy eyes. A sample of 55 monozygotic and 50 dizygotic healthy twin pairs aged 20-46, all having the same sex within pairs (47 pairs were male) had optic discs measured from colour fundus photographs according to the Wisconsin Protocol. Structural equation modelling was used to estimate the relative contribution of genetic and environmental factors to the phenotype. Disc dimensions did not vary significantly by age or sex. After adjusting for age and sex, additive genetic factors (i.e. heritability) explained 77% (95% CI: 65-85%) of variation of vertical disc diameters, whereas estimated unshared environmental effect was 23% (95% CI: 15-35%). For vertical cup diameters, heritability accounted for 70% (95% CI: 55-80%) and environmental factors 30% (95% CI: 20-45%). For cup/disc ratio, additive genetic and unshared environmental factors explained 66% (95% CI: 48-77%) and 34% (95% CI: 23-52%) of the variations, respectively. In this healthy twin sample, we found that three quarters of the variations in vertical optic disc and optic cup diameters were attributable to genetic influence.

Socioeconomic status and subclinical atherosclerosis in older adults

Objective This study investigated the long-term effects of socioeconomic status (SES) on atherosclerosis. Methods Data from the Epidemiology of Hearing Loss Study and the Beaver Dam Eye Study (Beaver Dam, WI, 1998–2000), were used to examine adult SES (education, household income, and longest-held job) and childhood SES (household density and parental home ownership at age 13) associations with carotid intima-media thickness (IMT) and carotid plaque in a cohort of 2042 men and women aged 53 to 94 years. Results For education, income, and occupation (women), those in the lowest SES group had statistically larger age-sex-adjusted IMT than those in the highest SES group (< 12 vs. > 12 years education: 0.92 vs. 0.86 mm respectively, P < 0.0001), (<$10,000 vs. >$45,000: 0.97 vs. 0.87 mm, P < 0.0001), (operator/fabricator/labor vs. manager/professional: 0.89 vs. 0.82 mm, P < 0.001). Associations were similar using carotid plaque as the outcome. Participants with low levels of both adult and childhood SES measures had age-sex-adjusted IMT greater than those with persistently high levels of SES (0.93 vs. 0.84 mm, P < 0.0001). Conclusions Measures of SES at two points in the life-span were associated with subclinical atherosclerosis.

15-Year Cumulative Incidence and Associated Risk Factors for Retinopathy in Nondiabetic Persons

To investigate the relationship of systemic factors to the 15-year cumulative incidence of retinopathy in nondiabetic persons in the Beaver Dam Eye Study. 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. 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. 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.

Cataract frequency and light scattering profiles in retired members of light protected communities ‐ The Irish Nun Eye Study (INES)

Abstract Purpose Investigation of cataract frequencies, yellow discoloration and light scattering profiles in the lenses of a subset of nuns from the Irish Nun Eye Study (INES) correlated to age and outdoor activity. Methods After obtaining informed consent, the anterior eye segment of 144 retired nuns from contemplative and missionary convents in Northern Ireland and the Republic of Ireland were monitored with a Scheimpflug camera (Pentacam HR®, Oculus, Wetzlar, Germany). Images of the cornea and lens were recorded automatically in 25 meridians in mydriasis, using the recording algorithm of the camera. In addition retro‐images of the lenses were recorded using the Neitz Cataract screener and lens discoloration was recorded using a manual slitlamp and the LOCS III grading system. Image analysis was performed using special analytical software (BIOM®) and cataract classification was done using the Bonn cataract classification system. Results Age‐related light scattering increase is most pronounced in the anterior deep cortex and the anterior nuclear shell of the lenses and is generally lowest in the posterior nuclear shell. Cortical cataracts were the most frequent type in this study, the highest frequency found in the lower nasal quadrant followed by the lower temporal quadrant. Pure subcapsular cataracts have not been found in this study. The increase in yellow discoloration correlated to the increase in nuclear light scattering. Nuns with cortical cataracts had less discoloration, but were also younger. Conclusion The frequency of nuclear cataracts was lower in the INES cohort was lower, but the amount of cortical cataracts was similar to other studies like Beaver Dam Eye Study. The increases in nuclear light scattering and discoloration correlated with age and exposure index. The data from the INES study support the hypothesis that light protection has a positive effect on the frequencies of nuclear and subcapsular cataracts as well as on lens discoloration. The Pentacam HR® provided better documentation of lens transmission characteristics than the Neitz cataract scanner.

The Prevalence of Macular Telangiectasia Type 2 in the Beaver Dam Eye Study

To examine the prevalence of macular telangiectasia type 2 and lesions characterizing it. Population-based cohort study. setting: City and township of Beaver Dam, 1988-1990. study population: A total of 4790 people 43-86 years of age. observation procedure(s): Grading from stereoscopic fundus photographs to measure macular telangiectasia type 2. main outcome measure: Prevalent macular telangiectasia type 2. Macular telangiectasia type 2 was present at baseline in 0.1% of the population (95% confidence interval [CI] 0.09, 0.1). The frequencies of loss of retinal transparency, crystals in the inner retinal layers, blunted retinal vessels, localized intraretinal pigment migration in the juxtafoveolar region, and presence of yellow deposits and lamellar holes in the foveal area in those without macular telangiectasia type 2 varied from 0.06% for retinal telangiectatic vessels to 1.2% for lamellar holes. Smoking was associated with pigment clumping (odds ratio [OR] per pack year 1.02; 95% CI 1.00, 1.03; P = .02), retinal pigment epithelial (RPE) depigmentation (OR 1.02 per pack year; 95%CI 1.00, 1.04; P = .02), loss of transparency (OR 1.02 per pack year; 95% CI 1.00, 1.03; P = .008), and the presence of a yellow spot in the fovea (OR 2.24 current vs past or never smoker; 95% CI 1.29, 3.89; P = .004), but not with presence of macular telangiectasia type 2 (OR 2.72; 95% CI 0.45, 16.28; P = .27). The prevalence of macular telangiectasia type 2 (0.1%) is higher than previously thought. These data are useful in estimating the burden of this condition in the population. The role of smoking in the development of macular telangiectasia type 2 requires further study.

Retrodots in the Lens in the Beaver Dam Eye Study Cohort

To determine the prevalence of retrodots in the lens and the association of these lesions to age-related cataract, and to assess their association with visual impairment and contrast sensitivity. Longitudinal epidemiologic study. The Beaver Dam Eye Study cohort. Eye examinations including grading of standard photographs of the lens and measures of visual function. Statistical associations of retrodots with nuclear, cortical, and posterior subcapsular cataracts and with incident visual impairment and impairment of contrast sensitivity. The prevalence of retrodots at the baseline examination increased with age from 1.68% in those 43 to 54 years of age to 31.20% in those ≥ 75 years of age. After controlling for age, there was no significant difference in the prevalence of retrodots between men and women. The odds ratio (OR) for visual impairment associated with retrodots was 2.22 (95% confidence interval [CI], 1.80-2.75) after controlling for age-related cataracts and other associated characteristics. The association with impaired contrast sensitivity was not significant. Retrodots were not significantly associated with incidence of any type of age-related cataract. The 15-year cumulative incidence of retrodots in right eyes increased with age from 9.3% in those 43 to 54 years of age to 21.1% in those ≥ 75 years of age. In addition to age, incidence of retrodots was independently associated with smoking (OR, 1.27; 95% CI, 1.04-1.56 for ever vs never smoking). Retrodots are frequently occurring age-related lens opacities that are associated with decreased vision independent of the presence of age-related cataract. Their incidence is associated with smoking. Further research to determine the underlying process leading to retrodots is necessary before efforts to develop preventions are undertaken.

Serum Calcium and Breast Cancer Risk in a Prospective Cohort Study

Abstract Calcium has anti-proliferative and pro-differentiation effects on mammary cells in vitro and can inhibit the development of mammary tumors in mice. While there is some epidemiologic evidence for an inverse relation between dietary calcium intake and breast cancer risk, only one previous study has examined serum calcium levels in relation to breast cancer risk. We investigated this relation in a prospective cohort study of 2,762 women, aged 43–86, who were enrolled in the Beaver Dam Eye Study in 1988 and followed for up to 19 years. We found no evidence for an association between breast cancer risk and either total (hazard ratio, HR = 0.98; 95% CI: 0.60–1.60; 4 th vs. 1 st quartile) or ionized (HR = 0.85; 95% CI: 0.53, 1.38; 4 th vs. 1 st quartile) serum calcium levels. Additionally, we found no evidence for an association among subgroups defined by menopausal status and body mass index.

Smoking and retinal vein occlusions. The Beijing Eye Study

Dear Editor, One of the most common ocular vascular diseases is retinal vein occlusion, the prevalence of which has been estimated to range from 0.3% to 1.6% in recent populationbased studies, such as the Blue Mountains Eye Study [1], the Beaver Dam Eye Study [2], a combined analysis of the Atherosclerosis Risk in Communities and Cardiovascular Health Studies [3], and the Singapore Malay Eye Study [4]. Considering that smoking is generally one of the major risk factors for vascular diseases, we addressed in our study whether smoking is associated with the prevalence of retinal vein occlusions. The Beijing Eye Study is a population-based study, which was first performed in 2001 and included 4,439 subjects (response rate: 83.4%) out of 5,324 subjects invited to participate, with an age of 40+ years. The study was repeated in 2006, with 3,251 subjects participating (response rate: 73.2%). The Medical Ethics Committee of the Beijing Tongren Hospital had approved the study protocol. The study has been described in detail recently [5]. Using fundus photographs (fundus camera: CR6-45NM, Canon Inc., USA), the prevalence of retinal vein occlusions was determined [5]. Recent retinal vein occlusions were characterized by the presence of retinal edema, optic disc hyperemia or edema, scattered superficial or deep hemorrhages, and venous dilatation. Old retinal vein occlusions were characterized by occluded and sheathed retinal veins. Additionally, we measured the systolic and diastolic blood pressure, and body height and body weight. Fasting blood samples were biochemically examined, and information was obtained about smoking habits. Glaucoma was defined by the appearance of the optic nerve head, as described in detail recently [5]. The study sample consisted of 3,214 subjects with a mean age of 55.3±10.0 years (range: 40–84 years) and a mean refractive error of −0.36±2.22 diopters (−20.1 diopters to +7.50 diopters). A retinal vein occlusion was detected in 37 subjects (1.2%). Out of the 3,214 subjects, 1,042 participants (32.4%) were current smokers (n=725; 16.3 % of the study population) or former smokers (n=317; 7.1% of the study population). In univariate analysis, prevalence of retinal vein occlusions was significantly associated with higher age (P<0.001), body mass index (P=0.001), mean arterial blood pressure (P=0.002), presence of glaucomatous optic nerve damage (P<0.001), and former smoking (P=0.002). In univariate analysis, retinal vein occlusions were not significantly associated with smoking as a whole group [P=0.16; odds ratio (OR): 1.60; 95% confidence interval (CI): 0.83, 3.07], nor with current smoking (P=0.43; OR: 0.66; 95% CI: 0.28, 1.59), level of education (P=0.15), gender (P=0.68), urban versus rural region (P=0.77), fasting blood levels of glucose Proprietary interest none

Multiple sensory impairment and quality of life

Purpose: To evaluate the independent impact of vision, hearing, and olfactory impairment on quality of life.Methods: Subjects (n = 1854, mean age = 67 years) were participants in the 1998–2000 and 2003–05 examinations of the Epidemiology of Hearing Loss Study and Beaver Dam Eye Study, population-based, prospective studies set in Beaver Dam, Wisconsin. Sensory capacities were measured in 1998–2000 and quality of life was measured in 2003–05. Vision impairment was assessed using current binocular visual acuity and contrast sensitivity. Hearing impairment was defined by the pure tone threshold average and word recognition scores in competing message and olfaction was measured with the San Diego Odor Identification Test. The Short Form 36 Health Survey (SF-36) was used to assess quality of life.Results: Significant independent effects of vision impairment and hearing impairment on the SF-36 social functioning domain score were observed (P < 0.01). The adjusted mean social functioning score for participants with vision and hearing impairment was 5.9 units lower than the mean score in participants with no vision and hearing impairment. A significant independent effect of vision impairment was also observed for the physical functioning and mental health domains (P < 0.01). Olfaction impairment was not significantly associated with the SF-36 indices.Conclusions: Impairments in vision and hearing demonstrated independent effects on quality of life. The impact was observed for physical and emotional health (vision) and social functioning (vision and hearing). Evaluation and rehabilitation of sensory deficits may contribute to an improvement in functioning and well-being in the later years of life.

Examining the relative influence of familial, genetic, and environmental covariate information in flexible risk models

We present a method for examining the relative influence of familial, genetic, and environmental covariate information in flexible nonparametric risk models. Our goal is investigating the relative importance of these three sources of information as they are associated with a particular outcome. To that end, we developed a method for incorporating arbitrary pedigree information in a smoothing spline ANOVA (SS-ANOVA) model. By expressing pedigree data as a positive semidefinite kernel matrix, the SS-ANOVA model is able to estimate a log-odds ratio as a multicomponent function of several variables: one or more functional components representing information from environmental covariates and/or genetic marker data and another representing pedigree relationships. We report a case study on models for retinal pigmentary abnormalities in the Beaver Dam Eye Study. Our model verifies known facts about the epidemiology of this eye lesion--found in eyes with early age-related macular degeneration--and shows significantly increased predictive ability in models that include all three of the genetic, environmental, and familial data sources. The case study also shows that models that contain only two of these data sources, that is, pedigree-environmental covariates, or pedigree-genetic markers, or environmental covariates-genetic markers, have comparable predictive ability, but less than the model with all three. This result is consistent with the notions that genetic marker data encode--at least in part--pedigree data, and that familial correlations encode shared environment data as well.

Heritability Analysis of Spherical Equivalent, Axial Length, Corneal Curvature, and Anterior Chamber Depth in the Beaver Dam Eye Study

To examine genetic influences for quantitative refraction. Spherical equivalent and its related binary traits of myopia and hyperopia are highly correlated within families. Many linkage regions have been reported for myopia, high myopia, and quantitative refraction. However, the measured phenotype of spherical equivalent is in large part dictated by the relationship between the underlying optical components of axial length, corneal curvature, and anterior chamber depth. Using data from the fourth visit of the Beaver Dam Eye Study, we conducted familial correlation and heritability analysis of quantitative spherical equivalent, axial length, anterior chamber depth, and corneal curvature using data from 715 individuals in 189 pedigrees. Overall, every trait was highly heritable. Heritability estimates were 0.58 (SE 0.13) for spherical equivalent after adjustment for age, education, and nuclear sclerosis; 0.95 (SE 0.11) for corneal curvature after adjustment for height; 0.67 (SE 0.14) for axial length after adjustment for height and education; and 0.78 (SE 0.14) for anterior chamber depth after adjustment for age, education, height, and nuclear sclerosis. Refraction and the underlying traits of axial length, corneal curvature, and anterior chamber depth are highly heritable. Genetic analysis of these traits may provide greater insight into the development of refractive errors.

Determinants of Retinal Microvascular Architecture in Normal Subjects

Recent studies have shown that changes in the retinal microvasculature predict cardiovascular disease (CVD); however, little is known regarding influences on the retinal microvasculature in healthy people without overt cardiovascular or metabolic disease. We used a semiautomated computerized technique to analyze digitized retinal photographs from a total of 167 healthy people (age range, 45-75 years; 83 female), without clinical CVD, diabetes, or hypertension, randomly sampled from the population-based Beaver Dam Eye Study. We assessed arteriolar and venular narrowing, arteriolar optimality deviation, and other quantitative aspects of the retinal microvasculature. Arterioles were significantly narrower and longer, had wider branching angles, and were more tortuous than venules. Increased arteriolar length to diameter ratio (an index of ratio arteriolar narrowing) was positively and independently associated with older age and elevated systolic blood pressure. Arteriolar optimality deviation (an index of microvascular endothelial dysfunction) increased with greater body mass index. Current smoking and increased white blood cell (WBC) count was associated with wider venules. After controlling for smoking, WBC was no longer a significant predictor of venular diameter. CVD risk factors are associated with retinal microvascular changes in healthy individuals without evidence of CVD, diabetes, or hypertension. CVD risk factors have different influences on the arteriolar and venular bed.