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Showing papers by "Ronald Klein published in 2005"


Journal Article•DOI•
TL;DR: This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.
Abstract: OBJECTIVE To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD). METHODS Following development of a detailed scale for individual eyes based on gradings of fundus photographs in the Age-Related Eye Disease Study, rates of progression to advanced AMD were assessed in cross-tabulations of presence or absence in each eye of 2 easily identified retinal abnormalities, drusen and pigment abnormalities. Large drusen and any pigment changes were particularly predictive of developing advanced AMD. RESULTS The scoring system developed for patients assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125 microm, width of a large vein at disc margin) drusen and 1 risk factor for the presence of any pigment abnormality. Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. For persons with no large drusen, presence of intermediate drusen in both eyes is counted as 1 risk factor. CONCLUSION This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.

700 citations


Journal Article•DOI•
TL;DR: In this article, the authors describe the association of demographic, behavioral, medical, and non-retinal ocular factors with the incidence of neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA) in the AREDS, a randomized trial of antioxidants and zinc supplementation prophylaxis for development of advanced AMD.

648 citations


Journal Article•DOI•
TL;DR: A fundus photographic severity scale for age-related macular degeneration (AMD) was developed in this article, where the severity of drusen characteristics and pigmentary abnormalities at baseline and development of advanced AMD within 5 years of follow-up were investigated.
Abstract: Objective To develop a fundus photographic severity scale for age-related macular degeneration (AMD). Methods In the Age-Related Eye Disease Study, stereoscopic color fundus photographs were taken at baseline, at the 2-year follow-up visit, and annually thereafter. Photographs were graded for drusen characteristics (size, type, area), pigmentary abnormalities (increased pigment, depigmentation, geographic atrophy), and presence of abnormalities characteristic of neovascular AMD (retinal pigment epithelial detachment, serous or hemorrhagic sensory retinal detachment, subretinal or sub-retinal pigment epithelial hemorrhage, subretinal fibrous tissue). Advanced AMD was defined as presence of 1 or more neovascular AMD abnormalities, photocoagulation for AMD, or geographic atrophy involving the center of the macula. We explored associations among right eyes of 3212 participants between severity of drusen characteristics and pigmentary abnormalities at baseline and development of advanced AMD within 5 years of follow-up. Results A 9-step severity scale that combines a 6-step drusen area scale with a 5-step pigmentary abnormality scale was developed, on which the 5-year risk of advanced AMD increased progressively from less than 1% in step 1 to about 50% in step 9. Among the 334 eyes that had at least a 3-step progression on the scale between the baseline and 5-year visits, almost half showed stepwise progression through intervening severity levels at intervening visits. Replicate gradings showed agreement within 1 step on the scale in 87% of eyes. Conclusions The scale provides convenient risk categories and has acceptable reproducibility. Progression along it may prove to be useful as a surrogate for progression to advanced AMD.

581 citations


Book Chapter•DOI•
TL;DR: Long-term epidemiologic studies have provided information on the distribution and the natural history of AMD and its associated risk factors, but it is not known what effect reduction of blood pressure and the cessation of smoking might have on the incidence and progression of AMD.
Abstract: For more than two decades, researchers have sought to identify "risk factors" for age-related macular degeneration (AMD), a major cause of irreversible vision loss in the Western world, particularly in the elderly. Two issues have complicated this search: failure to differentiate between different stages of AMD and misinterpretation of measures of association (odds ratios) and risk (risk ratios) derivable from different research designs. Fortunately, in more recent epidemiologic studies, more attention has been given to these issues. Three groups of potential "risk factors" that have been studied were reviewed: those known to be risk factors for cardiovascular disease, environmental factors, and racial and ethnic factors. Of these, only tobacco smoking, a known risk factor for cardiovascular disease, has been demonstrated to be associated with AMD consistently across many studies of different design, carried out within different populations. The available evidence supports at least a doubling of risk of late AMD associated with long-term smoking, a factor that is under the control of the individual. The preponderance of evidence has not supported other factors to the same degree. Presently, racial and ethnic factors are high priorities for further research.

426 citations


Journal Article•DOI•
TL;DR: Greater frailty was associated with greater likelihood of concurrent medical conditions and with decreased survival over an interval of 412 years after adjusting for age, sex, hypertension, diabetes, and cardiovascular disease.

258 citations


Journal Article•DOI•
TL;DR: Reduced systemic blood pressure is associated with reduced intraocular pressure and this finding should be evaluated in other studies, especially with respect to the possibility of resultant decreased risk of open angle glaucoma.
Abstract: Aim: To investigate the relation between change in systemic blood pressures and change in intraocular pressure. Methods: This was a population based study of people 43–86 years old living in Beaver Dam, Wisconsin. Measurements at baseline (1988–90) and 5 year follow up of systemic blood pressures, intraocular pressures, and history of use of blood pressure medications. Results: Intraocular pressures were significantly correlated with systolic and diastolic blood pressures at both baseline and follow up. There were significant direct correlations between changes in systemic blood pressures and changes in intraocular pressure. There was a 0.21 (95% CI: 0.16 to 0.27) mm Hg increase in IOP for a 10 mm Hg increase in systolic and 0.43 (0.35 to 0.52) mm Hg increase in IOP for a 10 mm Hg increase in diastolic blood pressure. Further adjustment for diabetes and medication use did not alter these associations. Decreased systolic or diastolic blood pressures of more than 10 mm Hg over 5 years were significantly associated with decreased IOP. Conclusions: Reduced systemic blood pressure is associated with reduced intraocular pressure. This finding should be evaluated in other studies, especially with respect to the possibility of resultant decreased risk of open angle glaucoma.

256 citations


Journal Article•DOI•
TL;DR: Generalized retinal arteriolar narrowing, an indicator of localized vascular change, is significantly associated with optic nerve damage caused by OAG, and it is not clear whether such a retinalarteriolar change reflects an ischemic process leading to optic nerveDamage or results from loss of retinal neurons secondary to glaucoma.

255 citations



Journal Article•DOI•
TL;DR: A meta- analysis of six AMD genome screens is performed using the genome-scan meta-analysis method, which allows linkage results from several studies to be combined, providing greater power to identify regions that show only weak evidence for linkage in individual studies.
Abstract: A genetic contribution to the development of age-related macular degeneration (AMD) is well established. Several genome-wide linkage studies have identified a number of putative susceptibility loci for AMD but only a few of these regions have been replicated in independent studies. Here, we perform a meta-analysis of six AMD genome screens using the genome-scan meta-analysis method, which allows linkage results from several studies to be combined, providing greater power to identify regions that show only weak evidence for linkage in individual studies. Results from non-parametric analysis for a broad AMD clinical phenotype (including two studies with quantitative traits) were extracted. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted according to study size and summed across all studies; the summed rank (SR) for each bin was assessed empirically for significance using permutation methods. A high SR indicates a region with consistent evidence for linkage across studies. The strongest evidence for an AMD susceptibility locus was found on chromosome 10q26 where genome-wide significant linkage was observed (P=0.00025). Several other regions met the empirical significance criteria for bins likely to contain linked loci including adjacent pairs of bins on chromosomes 1q, 2p, 3p and 16. Several of the regions identified here showed only weak evidence for linkage in the individual studies. These results will help prioritize regions for future positional and functional candidate gene studies in AMD.

246 citations


Journal Article•DOI•
TL;DR: In older Australians without diabetes, retinopathy signs predict stroke or stroke-related death independent of traditional stroke risk factors.
Abstract: Objective: The purpose of this study was to assess the relation of retinal microvascular signs and incident stroke and stroke mortality in an older population. Methods: The authors took retinal photographs on baseline participants (3,654 patients aged 49+ years) of the Blue Mountains Eye Study (1992 to 1994). They assessed the presence of retinopathy (microaneurysms, retinal hemorrhages) in participants without diabetes and retinal arteriolar signs in all participants using standardized grading protocols. Incident stroke/TIA/cerebrovascular death (combined stroke events) were identified at follow-up examinations during 1997 to 1999. Results: During a 7-year period, 859 participants died, 97 (11.3%) of which died of cerebrovascular causes. Of survivors, 24 had confirmed incident stroke, and 11 had incident TIA. Combined stroke events were more frequent in participants with retinopathy (5.7%), with moderate/severe arteriovenous nicking (4.2%), or with focal arteriolar narrowing (7.2%) compared with those without (1.9%). After controlling for age, sex, systolic blood pressure, smoking, and self-rated health, retinopathy was significantly associated with combined stroke events (relative risk [RR] 1.7, 95% CI 1.0 to 2.8) in persons without diabetes. This association was stronger in those without severe hypertension (RR 2.7, CI 1.2 to 6.2) or in persons with two or more retinal microvascular signs (RR 2.7, CI 1.5 to 5.2). Generalized or focal arteriolar narrowing or arteriovenous nicking was not independently associated with combined stroke events after multivariate adjustment. Conclusions: In older Australians without diabetes, retinopathy signs predict stroke or stroke-related death independent of traditional stroke risk factors.

220 citations


Journal Article•DOI•
05 Jan 2005-JAMA
TL;DR: Retinopathy is an independent predictor of CHF, even in persons without preexisting coronary heart disease, diabetes, or hypertension, which suggests that microvascular disease may play an important role in the development of heart failure in the general population.
Abstract: ContextCongestive heart failure (CHF) affects a substantial proportion of adults including those without preexisting coronary heart disease. The pathogenesis of CHF is uncertain, but microvascular disease has been hypothesized as a possible factor.ObjectiveTo determine the relationship of retinopathy, a marker of systemic microvascular disease, to risk of CHF.Design, Setting, and ParticipantsPopulation-based, prospective 7-year cohort study in 4 US communities using the Atherosclerosis Risk in Communities Study database. Participants (n = 11 612, aged 49 to 73 years) had retinal photographs taken between 1993 and 1995. The photographs were graded according to a standardized protocol for the presence of retinopathy (eg, microaneurysms, retinal hemorrhages, soft exudates), arteriovenous nicking, focal arteriolar narrowing, and generalized arteriolar narrowing.Main Outcome MeasuresAssociation between retinopathy and incident CHF, identified from hospitalization and death records.ResultsThe 7-year cumulative incidence of CHF was 5.4% (492 events). Participants with retinopathy had a higher incidence of CHF compared with those without retinopathy (15.1% vs 4.8%, P<.001). After controlling for age, sex, race, preexisting coronary heart disease, mean arterial blood pressure, diabetes, glucose level, cholesterol level, smoking, body mass index, and study site, the presence of retinopathy was associated with a 2-fold higher risk of CHF (relative risk, 1.96; 95% confidence interval, 1.51-2.54). Among participants without preexisting coronary heart disease, diabetes, or hypertension, retinopathy was associated with a 3-fold higher risk of CHF (relative risk, 2.98; 95% confidence interval, 1.50-5.92).ConclusionsRetinopathy is an independent predictor of CHF, even in persons without preexisting coronary heart disease, diabetes, or hypertension. This suggests that microvascular disease may play an important role in the development of heart failure in the general population. Some asymptomatic persons with retinopathy on an ophthalmologic examination may benefit from further assessment of CHF risk.

Journal Article•DOI•
TL;DR: Retinal microvascular abnormalities defined as retinopathy were significantly associated with renal function deterioration, and the findings suggest that systemic microv vascular disease may be associated with progressive renal dysfunction in the elderly population.

Journal Article•DOI•
TL;DR: Many measures of general quality of life and functional activities were related to age-related eye diseases, but few associations remained significant after adjustments for vision and other comorbidities.
Abstract: Objective To examine the associations of measures of quality of life (Medical Outcomes Study Short Form Health Survey) and functional activities (activities of daily living, instrumental activities of daily living, and visual function) in persons with and without age-related eye diseases. Methods Two thousand, six hundred seventy persons participated in the 1998 through 2000 examinations of both the Beaver Dam Eye Study and the Epidemiology of Hearing Loss Study. Age-related eye disease (age-related maculopathy, cataract, diabetic retinopathy, glaucoma, macula edema, occlusions, amblyopia, and macular holes) were assessed by fundus, slitlamp, and retroilluminated photographs and self-reported ocular history. Also administered was a standard interview that included the Medical Outcomes Study Short Form Health Survey, activities of daily living, instrumental activities of daily living, and visual function questionnaires and information on other medical conditions. Results After controlling for age and sex, we found that persons with an age-related eye disease had decreased scores in almost all the domains of the Medical Outcomes Study Short Form Health Survey, and persons with eye disease in both eyes had poorer scores than persons with eye disease in only 1 eye. Stratifying by age-related maculopathy and central cataract yielded similar results. Further adjustment for current visual acuity and the number of comorbid conditions explained most associations. Several of the mental scales were still marginally significantly lower ( P Conclusions Many measures of general quality of life and functional activities were related to age-related eye diseases, but few associations remained significant after adjustments for vision and other comorbidities. Our data are compatible with the notion that decreased visual function, irrespective of the pathologic reason for the decrease, is associated with diminished quality of life and functional activities of living.


Journal Article•DOI•
TL;DR: Retinal arteriolar narrowing is related to risk of incident diabetes, and a possible link between systemic arteriole-to-venule ratio narrowing associated with hypertension and diabetes development is suggested.
Abstract: Background Microvascular disease and hypertension have been linked with risk of diabetes mellitus. We examined the association of retinal arteriolar narrowing, a marker of chronic hypertension, with incident diabetes. Methods Prospective cohort study of 3251 nondiabetic persons aged 43 to 86 years living in Wisconsin. The diameters of retinal vessels were measured from baseline retinal photographs of participants. Retinal measurements were summarized as the retinal arteriole-to-venule ratio, with smaller ratios indicating narrower arteriolar diameters. Incident diabetes cases were ascertained at the 5-year and 10-year follow-up examinations. Results There were 249 incident diabetes cases. Participants with narrower retinal arteriolar diameters had a higher incidence of diabetes (cumulative incidences of 5.1%, 7.0%, 9.2%, and 11.7%, comparing decreasing quartiles of arteriole-to-venule ratio). After controlling for baseline casual blood glucose level, glycosylated hemoglobin level, body mass index, and other risk factors, retinal arteriolar narrowing was significantly associated with risk of incident diabetes (multivariable-adjusted relative risk, 1.53; 95% confidence interval, 1.03-2.27; comparing smallest to largest arteriole-to-venule ratio quartiles). Participants with both hypertension and retinal arteriolar narrowing had a 3-fold higher risk of incident diabetes (multivariable-adjusted relative risk, 3.41; 95% confidence interval, 1.66-6.98) than normotensive participants without arteriolar narrowing. Conclusions Retinal arteriolar narrowing is related to risk of incident diabetes. These data suggest a possible link between systemic arteriolar narrowing associated with hypertension and diabetes development.

Journal Article•DOI•
01 Feb 2005-Diabetes
TL;DR: A significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients is demonstrated, while controlling for other risk factors.
Abstract: Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants (n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged >/=16 years and had 2-20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume [Vv(Mes/glom)] and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients.

Journal Article•DOI•
TL;DR: A higher frequency of severe diabetic retinopathy was found in the Hispanic and African-American patients at entry into the VADT that is not accounted for by traditional risk factors for diabetic Retinopathy, and these substantial ethnic differences remain to be explained.
Abstract: OBJECTIVE—The Veterans Affairs Diabetes Trial (VADT) cohort is enriched with ∼20% Hispanics and 20% African Americans, affording a unique opportunity to study ethnic differences in retinopathy. RESEARCH DESIGN AND METHODS—Cross-sectional analyses on the baseline seven-field stereo fundus photos of 1,283 patients are reported here. Diabetic retinopathy scores are grouped into four classes of increasing severity: none (10–14), minimal nonproliferative diabetic retinopathy (NPDR) (15–39), moderate to severe NPDR (40–59), and proliferative diabetic retinopathy (60+). These four groups have also been dichotomized to none or minimal (10–39) and moderate to severe diabetic retinopathy (40+). RESULTS—The prevalence of diabetic retinopathy scores >40 was higher for Hispanics (36%) and African Americans (29%) than for non-Hispanic whites (22%). The difference between Hispanics and non-Hispanic whites was significant (P 40 was significantly higher in African Americans than in non-Hispanic whites (P CONCLUSIONS—In addition to many well-known associations with retinopathy, a higher frequency of severe diabetic retinopathy was found in the Hispanic and African-American patients at entry into the VADT that is not accounted for by traditional risk factors for diabetic retinopathy, and these substantial ethnic differences remain to be explained.

Journal Article•DOI•
TL;DR: The computer simulation model accurately predicted survival and the cardiovascular, microvascular, and neuropathic complications observed in the older-onset diabetic population studied in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) over 10 years.
Abstract: OBJECTIVE —To develop and validate a comprehensive computer simulation model to assess the impact of screening, prevention, and treatment strategies on type 2 diabetes and its complications, comorbidities, quality of life, and cost. RESEARCH DESIGN AND METHODS —The incidence of type 2 diabetes and its complications and comorbidities were derived from population-based epidemiologic studies and randomized, controlled clinical trials. Health utility scores were derived for patients with type 2 diabetes using the Quality of Well Being–Self-Administered. Direct medical costs were derived for managed care patients with type 2 diabetes using paid insurance claims. Monte Carlo techniques were used to implement a semi-Markov model. Performance of the model was assessed using baseline and 4- and 10-year follow-up data from the older-onset diabetic population studied in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). RESULTS —Applying the model to the baseline WESDR population with type 2 diabetes, we predicted mortality to be 51% at 10 years. The prevalences of stroke and myocardial infarction were predicted to be 18 and 19% at 10 years. The prevalences of nonproliferative diabetic retinopathy, proliferative retinopathy, and macular edema were predicted to be 45, 16, and 18%, respectively; the prevalences of microalbuminuria, proteinuria, and end-stage renal disease were predicted to be 19, 39, and 3%, respectively; and the prevalences of clinical neuropathy and amputation were predicted to be 52 and 5%, respectively, at 10 years. Over 10 years, average undiscounted total direct medical costs were estimated to be $53,000 per person. Among survivors, the average utility score was estimated to be 0.56 at 10 years. CONCLUSIONS —Our computer simulation model accurately predicted survival and the cardiovascular, microvascular, and neuropathic complications observed in the WESDR cohort with type 2 diabetes over 10 years. The model can be used to predict the progression of diabetes and its complications, comorbidities, quality of life, and cost and to assess the relative effectiveness, cost-effectiveness, and cost-utility of alternative strategies for the prevention and treatment of type 2 diabetes.

Journal Article•DOI•
TL;DR: More severe diabetic Retinopathy showed evidence of familial aggregation, but the occurrence of diabetic retinopathy per se did not, suggesting the factors involved in the onset of diabeticretinopathy may differ from those involved in its progression to more severe forms.
Abstract: OBJECTIVE—Diabetic retinopathy is a major cause of blindness. To determine whether retinopathy itself or only its severity aggregates in families, we examined the occurrence and severity of diabetic retinopathy in Mexican-American siblings with type 2 diabetes. RESEARCH DESIGN AND METHODS—Using stereoscopic fundus photography of seven standard fields, we measured retinopathy in 656 type 2 diabetic patients from 282 Mexican-American families from Starr County, Texas. Retinopathy severity was scored using the Early Treatment of Diabetic Retinopathy Study system and classified as no retinopathy, early nonproliferative diabetic retinopathy (NPDR-E), moderate-to-severe nonproliferative diabetic retinopathy (NPDR-S), or proliferative diabetic retinopathy (PDR). RESULTS—Of 249 siblings of randomly selected probands with retinopathy, 169 (67.9%) had retinopathy, compared with 95 of 125 siblings of unaffected probands (76.0%; P = 0.11). Proband retinopathy class was associated (P = 0.03) with sibling retinopathy class, with significant odds ratios (ORs) for NPDR-E versus no retinopathy (OR 0.57 [95% CI 0.35–0.93]) and PDR versus NPDR-E (2.02 [1.13–3.63]); the contrast of NPDR-S versus NPDR-E approached significance (1.78 [0.99–3.20]). With the more severe classes (PDR and NPDR-S) combined in one group and the less severe ones (none and NPDR-E) in another, more severe proband retinopathy was associated with more severe sibling retinopathy (1.72 [1.03–2.88]). CONCLUSIONS—More severe diabetic retinopathy showed evidence of familial aggregation, but the occurrence of diabetic retinopathy per se did not. The factors involved in the onset of diabetic retinopathy may differ from those involved in its progression to more severe forms.

Journal Article•DOI•
TL;DR: Serum C-reactive protein, amyloid A, interleukin-6, tumor necrosis factor-alpha, intracellular adhesion molecule, E-selectin, folate, and Chlamydia pneumoniae IgG antibody were not associated with either prevalent or incident ARM.

Journal Article•DOI•
TL;DR: The purpose of this research was to evaluate the relation between self-reported cardiovascular disease (CVD) and cochlear function in older adults.
Abstract: The purpose of this research was to evaluate the relation between self-reported cardiovascular disease (CVD) and cochlear function in older adults. The Epidemiology of Hearing Loss Study (EHLS) is an ongoing population-based study of hearing loss and its risk factors in Beaver Dam, Wisconsin. As part of the EHLS questionnaire, participants were asked about their cardiovascular medical history. CVD history was determined from questions regarding history of angina, myocardial infarction (MI), and stroke. Questions about the use of antihypertensive medication and blood pressure measurements determined the presence or absence of hypertension. Among the audiologic measures completed were distortion product otoacoustic emissions (DPOAEs). Cochlear function was measured using DPOAEs and participants were categorized as having (a) cochlear impairment, (b) possible cochlear impairment, or (c) no cochlear impairment. There were 1,501 participants with complete CVD and DPOAE data from the 1998-2000 examination phase. Women with a self-reported history of MI were twice as likely (age-adjusted odds ratio [OR] = 2.00, 95% confidence interval [CI] = 1.15-3.46) to have cochlear impairment than women without a history of MI. This association was not significant in men (age-adjusted OR = 0.98, 95% CI = 0.61-1.58). Additionally, no other CVD variables were associated with cochlear impairment. This study provides data on a possible sex-specific association between CVD and DPOAEs in older adults.

Journal Article•DOI•
TL;DR: The objective of the present research project was to systematically determine the prevalence of micro- and macrovascular complications among Aboriginal Canadians who have type 2 diabetes and to identify risk factors that are associated with these conditions.
Abstract: Despite a dramatically increasing burden of type 2 diabetes in Aboriginal Canadian communities (1–5), relatively little information is available regarding the prevalence of, and risk factors for, the complications of type 2 diabetes in this population (6). Although previous studies have documented micro- and macrovascular disease in Aboriginal Canadians with diabetes, the majority of these reports have relied heavily on hospital records, chart reviews, and disease registries (6). These approaches may underestimate the magnitude of the complications burden because only those with the severest disease are included, and standardized methods are infrequently used to document complications. The objective of the present research project was to systematically determine, using validated methods, the prevalence of micro- and macrovascular complications among Aboriginal Canadians who have type 2 diabetes and to identify risk factors that are associated with these conditions. The Sandy Lake Diabetes Complications Study has been presented in detail previously (6). Briefly, all community members known to have type 2 diabetes were invited to participate; 189 of 250 (76%) eligible subjects were enrolled, although the sample size varies given time-limited access to certain equipment. Participants were older than nonparticipants and more likely to be male but did not differ in diabetes treatment. Signed informed consent was obtained from all participants, and the study was approved by the Sandy Lake First Nation Band Council and the Mount Sinai Hospital Ethics Review Committee. We used validated measures to assess retinopathy, neuropathy, nephropathy, and cardiovascular disease risk factors, as described previously (6). Digital fundus photography was performed using a nonmydriatic retinal camera, with …

Journal Article•DOI•
TL;DR: The strong association between weight loss (likely involuntary) and mortality may be a useful way of estimating overall risks to longevity in populations.

Journal Article•DOI•
01 Aug 2005-Eye
TL;DR: Findings suggest that microvascular disease in the retina may result from processes distinct from dyslipidaemia, and elevated high-density lipoprotein cholesterol was associated with narrower retinal arterioles and venules and with increased odds of generalised arteriolar narrowing.
Abstract: There are few data on the effect of serum lipids on microvascular disease. This study assessed the relationships between serum lipid levels and microvascular disease, as seen in the retina, among participants who attended a population-based study in Australia (n=3654, aged 49+years). Diameters of retinal arterioles and venules were measured from digitised photographs of each participant to obtain an estimate of generalised arteriolar narrowing. Focal arteriolar narrowing, arteriovenous nicking, and retinopathy lesions (microaneurysms, haemorrhages, hard/soft exudates) were graded using a standard protocol. Fasting blood tests were performed in 89% of subjects. Adjusted means were calculated using general linear models. Logistic regression models were used to determine the odds ratios for retinal microvascular signs. After controlling for age, sex, body mass index, smoking, and mean arterial blood pressure, elevated high-density lipoprotein cholesterol was associated with narrower retinal arterioles (Ptrend=0.002) and venules (Ptrend=0.03) and with increased odds of generalised arteriolar narrowing (odds ratio 1.6, 95% confidence interval 1.1–2.2 for the highest vs the lowest quintile of high-density lipoprotein cholesterol). Serum triglyceride had a U-shaped relationship with venular diameter (Ptrend=0.003). We found no consistent pattern of association between serum total cholesterol or low-density lipoprotein cholesterol and any retinal microvascular signs. These findings suggest that microvascular disease in the retina may result from processes distinct from dyslipidaemia.

Journal Article•DOI•
TL;DR: Although early macular changes were very common among Hispanic people, the prevalence of late AMD was infrequent, and early AMD was strongly associated with age with a prevalence of 20% in the 50- to 59-year age group, increasing to 54% inThe group aged 80 years and older.
Abstract: Objective To report the prevalence of age-related macular degeneration (AMD) in a population-based sample of Hispanic individuals aged 50 years and older. Methods Proyecto VER (Vision and Eye Research) is a population-based study of blindness and visual impairment of Hispanic people in Arizona. Participants underwent complete ophthalmic evaluation, including stereoscopic fundus photography of fields 1, 2, and 4. All photographs for participants aged 50 years and older were graded using the Wisconsin Age-Related Maculopathy Grading system. The following signs were graded: drusen size, drusen type, and the area covered by drusen; pigmentary abnormalities; geographic atrophy; and exudative AMD. Results Sixty-seven percent (3178) of the original 4774 participants were 50 years of age or older. Of those, 92% (2928) had fundus photographs in at least 1 eye, and 95% (2780) of the photographs were of sufficient quality to grade early and late AMD. Outcome Measures The overall prevalence of late AMD was 0.5%. The prevalence increased from 0.1% in the 50- to 59-year age group to 4.3% in the group aged 80 years and older. Likewise, early AMD was strongly associated with age with a prevalence of 20% in the 50- to 59-year age group, increasing to 54% in the group aged 80 years and older. The prevalence of early AMD in Hispanic people was significantly higher than the reported prevalence in the white population. However, the prevalence of late AMD was lower than the estimates for the white population of the United States. Conclusions Although early macular changes were very common among Hispanic people, the prevalence of late AMD was infrequent. Further work is necessary to understand the underlying reasons for the different patterns of presentation of early and late signs of AMD among racial/ethnic groups and to characterize early AMD based on predictive value for severe disease in different populations.

Journal Article•DOI•
TL;DR: The segregation and familial correlation analyses of IOP suggest a polygenetic component with environmental influences, consistent with a multifactorial model of inheritance that may include multiple genes and environmental factors that contribute to IOP.
Abstract: PURPOSE. To investigate a potential genetic contribution to intraocular pressure (IOP), we performed a complex segregation analysis on 2337 individuals in 620 extended pedigrees ascertained through a population-based cohort, the Beaver Dam Eye Study (BDES). IOP is a principal risk factor for primary open-angle glaucoma (POAG) a leading cause of blindness worldwide. METHODS. Segregation analysis is an analytical method that provides statistical evidence supporting the involvement of a major gene or polygenes in a particular phenotype. Detailed medical histories and eye examinations were performed on all participants. From the two eyes, the higher IOP measurement was used as a continuous trait after adjustment for covariates. A genome-wide scan (GWS) using affected sib pair linkage analysis was performed on 218 sibling pairs. RESULTS. In this segregation analysis the model that allowed for an unmeasured major environmental effect plus a polygenic/ multifactorial effect provided the best fit and was the most parsimonious model. The lack of an adequate fit for the Mendelian single-gene models is consistent with a multifactorial model of inheritance that may include multiple genes and environmental factors that contribute to IOP. The results of the GWS yielded two novel loci as potential linkage regions for IOP on chromosomes 6 (P 0.008) and 13 (P 0.0007). Neither of these regions has previously been identified in GWS of POAG. CONCLUSIONS. The segregation and familial correlation analyses of IOP suggest a polygenetic component with environmental influences. The pilot linkage study further confirms the heterogeneity of IOP with the identification of two novel genetic loci. (Invest Ophthalmol Vis Sci. 2005;46:555‐560) DOI:

Journal Article•DOI•
TL;DR: The proposed criteria for computer classification produced results that are comparable with those provided by human experts and could become a useful clinical aid to physicians and a tool for screening, diagnosing, and classifying NPDR.
Abstract: Objective To propose methods for computer grading of the severity of 3 early lesions, namely, hemorrhages and microaneurysms, hard exudates, and cotton-wool spots, and classification of nonproliferative diabetic retinopathy (NPDR) based on these 3 types of lesions. Methods Using a computer diagnostic system developed earlier, the number of each of the 3 early lesions and the size of each lesion in the standard photographs were determined. Computer classification criteria were developed for the levels of individual lesions and for NPDR. Evaluation of the criteria was performed using 430 fundus images with normal retinas or any degree of retinopathy and 361 fundus images with no retinopathy or the 3 early lesions only. The results were compared with those of the graders at the University of Wisconsin Ocular Epidemiology Reading Center and an ophthalmologist. Main Outcome Measures Agreement rates in the classification of NPDR between the computer system and human experts. Results In determining the severity levels of individual lesions, the agreement rates between the computer system and the reading center were 82.6%, 82.6%, and 88.3% using the 430 images and 85.3%, 87.5%, and 93.1% using the 361 images, respectively, for hemorrhages and microaneurysms, hard exudates, and cotton-wool spots. When the “questionable” category was excluded, the corresponding agreement rates were 86.5%, 92.3%, and 91.0% using the 430 images and 89.7%, 96.3%, and 97.4% using the 361 images. In classifying NPDR, the agreement rates between the computer system and the ophthalmologist were 81.7% using the 430 images and 83.5% using the 361 images. Conclusions The proposed criteria for computer classification produced results that are comparable with those provided by human experts. With additional research, this computer system could become a useful clinical aid to physicians and a tool for screening, diagnosing, and classifying NPDR.

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TL;DR: The results of this segregation analysis support the involvement of genetic factors in the etiology of refractive error and are consistent with reports of linkage to multiple regions of the genome.
Abstract: Purpose Refractive errors, myopia, and hyperopia are common conditions requiring corrective lenses. The familial clustering of myopia has been well established. Several chromosomal regions have been linked to high myopia (12q, 17q, and 18q), to quantitative refraction among twins (3q, 4q, 8p, and 11p), and to families with moderate myopia (22q). This study examined the familial aggregation and pattern of inheritance of ocular refraction in an adult population, by using data from the Beaver Dam Eye Study. Methods Familial correlations were examined and segregation analysis was performed on the average refractive error measurements in the right and left eyes after adjustment for age, sex, and education. Analyses were based on 2138 individuals in 620 extended pedigrees with complete data on age, sex, education, and spherical equivalent. Results Substantial positive correlation was found between siblings (0.33), parents and offspring (0.17), and cousins (0.10) and lower correlation among avuncular pairs (0.08) after adjustment for age, sex, and years of education. The results of this segregation analysis do not support the involvement of a single major locus throughout the entire range of refractive error. However, models allowing for familial correlation, attributable in part to polygenic effects, provided a better fit to the observed data than models without a polygenic component, suggesting that several genes of modest effect may influence refractive error, possibly in conjunction with environmental factors. Conclusions These results support the involvement of genetic factors in the etiology of refractive error and are consistent with reports of linkage to multiple regions of the genome.

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TL;DR: In this article, the association between systemic and ocular comorbidity and visual impairment and self-reported visual function in Latino subjects was assessed using the National Eye Institute 25-item Visual Function Questionnaire (NEI-VFQ-25) and eye examination data.
Abstract: Objective To assess the association of self-reported systemic and ocular comorbid disease and visual function in Latino subjects. Methods National Eye Institute 25-item Visual Function Questionnaire (NEI-VFQ-25) and eye examination data were obtained from 5380 participants in the Los Angeles Latino Eye Study, a population-based prevalence study of eye disease in Latino subjects 40 years and older. We developed and contrasted 5 comorbidity measures. One-way analysis of variance was used to assess the association between comorbidity and visual impairment and self-reported visual function. Regression analyses determined the association of sociodemographic variables, clinical variables, and the best measure of comorbidity with the NEI-VFQ-25 composite score. The main outcome measure was self-reported visual function as assessed by the NEI-VFQ-25 composite score. Results On average, visual function subscale scores were lowest for those participants with the most systemic comorbid conditions (P Conclusions Self-reported systemic comorbidities were associated with self-reported visual function. This association was greater at more severe levels of visual impairment. Of the 5 comorbidity measures assessed, the measure that summed the number of self-reported systemic comorbidities correlated most with self-reported visual function.

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TL;DR: In this paper, the authors investigated the associations of measures of frailty to prevalent age-related maculopathy (ARM) and found a weak cross-sectional association of handgrip strength with ARM after controlling for co-morbid conditions.