scispace - formally typeset
Search or ask a question

Showing papers by "Ronald Klein published in 1993"


Journal Article
TL;DR: Two thirds of diabetic patients have objective evidence for some variety of neuropathy, but only about 20% have symptoms, and only 6% of IDDM and only 1% of NIDDM patients have sufficiently severe polyneuropathy to be graded stage 2b, and none were graded stage 3.
Abstract: The magnitude of the health problem from diabetic neuropathies remains inadequately estimated due to the lack of prospective population-based studies employing standardized and validated assessments of the type and stage of neuropathy as compared with background frequency. All Rochester, Minnesota, residents with diabetes mellitus on January 1, 1986, were invited to participate in a cross-sectional and longitudinal study of diabetic neuropathies (and also of other microvascular and macrovascular complications). Of 64,573 inhabitants on January 1, 1986 in Rochester, 870 (1.3%) had clinically recognized diabetes mellitus (National Diabetes Data Group criteria), of whom 380 were enrolled in the Rochester Diabetic Neuropathy Study. Of these, 102 (26.8%) had insulin-dependent diabetes mellitus (IDDM), and 278 (73.2%) had non-insulin-dependent diabetes mellitus (NIDDM). Approximately 10% of diabetic patients had neurologic deficits attributable to nondiabetic causes. Sixty-six percent of IDDM patients had some form of neuropathy; the frequencies of individual types were as follows: polyneuropathy, 54%; carpal tunnel syndrome, asymptomatic, 22%, and symptomatic, 11%; visceral autonomic neuropathy, 7%; and other varieties, 3%. Among NIDDM patients, 59% had various neuropathies; the individual percentages were 45%, 29%, 6%, 5%, and 3%. Symptomatic degrees of polyneuropathy occurred in only 15% of IDDM and 13% of NIDDM patients. The more severe stage of polyneuropathy, to the point that patients were unable to walk on their heels and also had distal sensory and autonomic deficits (stage 2b) occurred even less frequently–6% of IDDM and 1% of NIDDM patients. Overall, two thirds of diabetic patients have objective evidence for some variety of neuropathy, but only about 20% have symptoms, and only 6% of IDDM and only 1% of NIDDM patients have sufficiently severe polyneuropathy to be graded stage 2b, and none were graded stage 3. Approximately one quarter of patients had subclinical carpal tunnel syndrome, but only 7.7% had symptomatic carpal tunnel syndrome. Thus, diabetic peripheral neuropathy is frequent but less severe than generally thought. As generally believed, however, neuropathy, retinopathy, and nephropathy are significantly associated.

1,228 citations


Journal ArticleDOI
TL;DR: The magnitude of the health problem from diabetic neuropathies remains inadequately estimated due to the lack of prospective population-based studies employing standardized and validated assessments of the type and stage of neuropathy as compared with background frequency.
Abstract: The magnitude of the health problem from diabetic neuropathies remains inadequately estimated due to the lack of prospective population-based studies employing standardized and validated assessments of the type and stage of neuropathy as compared with background frequency. All Rochester, Minnesota, residents with diabetes mellitus on January 1, 1986, were invited to participate in a cross-sectional and longitudinal study of diabetic neuropathies (and also of other microvascular and macrovascular complications). Of 64,573 inhabitants on January 1, 1986 in Rochester, 870 (1.3%) had clinically recognized diabetes mellitus (National Diabetes Data Group criteria), of whom 380 were enrolled in the Rochester Diabetic Neuropathy Study. Of these, 102 (26.8%) had insulin-dependent diabetes mellitus (IDDM), and 278 (73.2%) had non-insulin-dependent diabetes mellitus (NIDDM). Approximately 10% of diabetic patients had neurologic deficits attributable to nondiabetic causes. Sixty-six percent of IDDM patients had some form of neuropathy; the frequencies of individual types were as follows: polyneuropathy, 54%; carpal tunnel syndrome, asymptomatic, 22%, and symptomatic, 11%; visceral autonomic neuropathy, 7%, and other varieties, 3%. Among NIDDM patients, 59% had various neuropathies; the individual percentages were 45%, 29%, 6%, 5%, and 3%. Symptomatic degrees of polyneuropathy occurred in only 15% of IDDM and 13% of NIDDM patients. The more severe stage of polyneuropathy, to the point that patients were unable to walk on their heels and also had distal sensory and autonomic deficits (stage 2b) occurred even less frequently--6% of IDDM and 1% of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

1,211 citations


Journal ArticleDOI
TL;DR: The authors believe data from the BDHOS will provide researchers and policy makers a reference col lection of vital statistics for health-related quality of life and provide a way to compare results from studies that utilize different indices from among the four principal measures of theBDHOS.
Abstract: The Beaver Dam Health Outcomes Study (BDHOS) is an ongoing longitudinal cohort study of health status and health-related quality of life for a random sample of adults (age range at interview was 45 to 89 years; mean = 64.1, SD = 10.8) in a community population. In a face-to-face interview lasting approximately an hour, each participant responds to several batteries of questions. Included are a history of chronic medical conditions, current medications, and past surgeries; the SF-36 (a general health-status questionnaire); the Quality of Well-being index; self-rated health status on a five-point scale from "excellent" to "poor"; and evaluation of current health using the method of time tradeoffs. The authors present results from 1,356 interviews on these four principal measures, reporting mean scores by sex, by age, and for persons reporting being affected by various medical conditions. They believe data from the BDHOS will provide researchers and policy makers a reference collection of vital statistics for health-related quality of life. Additionally, the data provide a way to compare results from studies that utilize different indices from among the four principal measures of the BDHOS.

792 citations


Journal ArticleDOI
TL;DR: Exposure to sunlight may be associated with age-related maculopathy, however, longitudinal studies of these associations are needed.
Abstract: • Objective. —To investigate the relationship of sunlight exposure with age-related maculopathy. This was investigated in the population-based Beaver Dam Eye Study. Design. —In this cross-sectional population-based study, questionnaire data about sunlight exposure were obtained. Stereoscopic color fundus photographs were graded to determine the presence of age-related maculopathy. Participants. —People aged 43 through 84 years who resided in Beaver Dam, Wis, between 1987 and 1988 were examined between 1988 and 1990. Results. —Light exposure was not associated with early age-related maculopathy in women. In men, after adjusting for age, the amount of time spent outdoors in summer was associated with increased retinal pigment (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.01 to 2.04). Wearing eyeglasses was inversely associated with increased retinal pigment (OR, 0.75; 95% CI, 0.58 to 0.97), and the use of hats and sunglasses was inversely associated with soft indistinct drusen (OR, 0.61; 95% CI, 0.38 to 0.98). The amount of leisure time spent outdoors in summer was significantly associated with exudative macular degeneration (OR, 2.26; 95% CI, 1.06 to 4.81) and late maculopathy (OR, 2.19; 95% CI, 1.12 to 4.25). There were no associations between estimated ambient UV-B exposure and age-related maculopathy. Conclusions. —These data suggest that exposure to sunlight may be associated with age-related maculopathy. However, longitudinal studies of these associations are needed.

384 citations


Journal ArticleDOI
TL;DR: It is suggested that exudative macular degeneration is associated with cigarette smoking and that different forms of maculopathy may have different etiologies.
Abstract: There are conflicting reports regarding the relation of cigarette smoking to age-related maculopathy, a major cause of blindness in the United States. In this report, the authors examined this association in people aged 43-86 years (n = 4,771) who participated in the Beaver Dam Eye Study, Beaver Dam, Wisconsin (1988-1990). Exposure data on cigarette smoking were derived from questions about present and past smoking, duration of smoking, and the number of cigarettes smoked per day. Age-related maculopathy status was determined by grading stereoscopic color fundus photographs using the Wisconsin Age-related Maculopathy Grading System. Smoking status, pack-years smoked, and current exposure to passive smoking were not associated with drusen characteristics (type, area, and confluence) or signs of early age-related maculopathy in any age-sex group studied, except for a higher frequency of increased retinal pigment in males who had ever smoked compared with those who had never smoked. The relative odds for exudative macular degeneration, one form of late age-related maculopathy, in females who were current smokers was 2.50 (95% confidence interval 1.01-6.20) compared with those who were ex-smokers or never smokers; for males, it was 3.29 (95% confidence interval 1.03-10.50). There was no significant relation between smoking status and pure geographic atrophy, another form of late age-related maculopathy. These results suggest that exudative macular degeneration is associated with cigarette smoking and that different forms of macular degeneration may have different etiologies.

301 citations


Journal ArticleDOI
TL;DR: The results suggest that the questionnaire produces nutrient estimates that rank individuals on the basis of intake of most nutrients similarly to estimates from multiple food records, suggesting overall good agreement in ranking.
Abstract: We evaluated the reproducibility of a modified version of the National Cancer Institute diet history questionnaire and also studied comparability of nutrient estimates from this questionnaire to those from four 2-d food records. Subjects (n = 211) were from a population-based sample of middle-aged and older adults participating in the Beaver Dam Eye Study in south-central Wisconsin. Median age-specific correlation coefficients between the questionnaire, administered twice at a 3-mo interval, were 0.8 in men and 0.7 in women (range = 0.5 to 0.9). Questionnaire estimates of protein, cholesterol, thiamin, niacin, iron and zinc were consistently lower than food record estimates whereas estimates of fat were higher. Correlation coefficients between estimates from the questionnaire and records were generally > 0.5, indicating overall good agreement in ranking. However, the range in correlation coefficients was wide [ranging from 0.06 for iron (without supplements) in middle-aged women to 0.8 for alcohol in middle-aged men and women]. Questionnaire estimates similarly classified persons into the lowest two food record quintiles of intake 50 to 93% of the time depending on nutrient. These results suggest that the questionnaire produces nutrient estimates that rank individuals on the basis of intake of most nutrients similarly to estimates from multiple food records.

281 citations


Journal ArticleDOI
TL;DR: The data suggest that most cardiovascular disease risk factors are not related to age-related maculopathy, and hematocrit values, leukocyte counts, and exudative macular degeneration.

270 citations



Journal ArticleDOI
TL;DR: It is suggested that individuals with insulin-dependent diabetes mellitus who have microalbuminuria may benefit from ophthalmologic follow-up as a marker for the risk of proliferative retinopathy developing.

154 citations


Journal ArticleDOI
TL;DR: The relationship between cigarette smoking behavior and lens opacities in cross-sectional data on 4,926 adults in Beaver Dam, Wisconsin suggested an etiologic effect, which would indicate another benefit of smoking cessation.

134 citations


Journal ArticleDOI
TL;DR: Findings suggest a relationship between controllable risk factors, blood pressure and GHb, and microalbuminuria in older-onset diabetic individuals.
Abstract: OBJECTIVE To examine the prevalence of microalbuminuria and the relationships of microalbuminuria to blood pressure and other risk factors. RESEARCH DESIGN AND METHODS Individuals diagnosed with diabetes at ≥30 yr of age either taking insulin ( n = 435) or not taking insulin ( n = 363), who were participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy, were examined during 1984-1986. Random urine samples were collected and an agglutination inhibition test was used to determine the presence of microalbuminuria, which is defined as ≥0.03 g/L but RESULTS The frequency of microalbuminuria was 29.2% in those individuals taking insulin and 22.0% in those not taking insulin. Microalbuminuria was significantly associated with the male sex, older age, higher systolic blood pressure, higher GHb, use of insulin, higher recent alcohol consumption, and a history of cardiovascular disease. CONCLUSIONS These findings suggest a relationship between controllable risk factors, blood pressure and GHb, and microalbuminuria in older-onset diabetic individuals.

Journal ArticleDOI
TL;DR: In this paper, the authors evaluated a possible association of glaucoma with alcohol ingestion and cigarette-smoking behavior and found that neither heavy drinking nor cigarette smoking behavior was related to the prevalence of open-angle glaucea.

Journal ArticleDOI
TL;DR: Results indicate that gp145trkB does not require p75LNGFR to form a functional receptor for BDNF in hippocampal pyramidal neurons, as determined by an increase in MAP2 phosphorylation in vitro.
Abstract: The trkB gene encodes a tyrosine kinase receptor, gp145trkB, for brain- derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). To understand the role of gp145trkB in the nervous system, we have investigated its expression in embryonic rat hippocampal pyramidal cell cultures and examined the effects of BDNF on signal transduction in the primary neurons. The expression of trkB transcripts was established by PCR analysis and in situ hybridization. In addition to gp145trkB, the pyramidal neuronal cultures expressed transcripts specific for the NT-3 receptor gp145trkC, but not for the high-affinity NGF receptor gp140trk or for p75LNGFR, a low-affinity receptor for all known members of the NGF family of neurotrophins including the gp145trkB ligands, BDNF and NT-4. The presence of gp145trkB receptors in the primary neuronal cultures was confirmed by immunocytochemical analysis in which > 90% of the cells stained with affinity-purified polyclonal antibodies to gp145trkB. Immunoblots using this antibody revealed a single approximately 140 kDa protein in both adult hippocampus and pyramidal cultures. Addition of recombinant BDNF to these cultures induced the tyrosine phosphorylation of gp145trkB, as determined by antiphosphotyrosine staining of gp145trkB immunoprecipitates. Moreover, BDNF treatment activated the microtubule-associated protein (MAP) kinases, as determined by an increase in MAP2 phosphorylation in vitro. Both the 41 and 44 kDa forms of MAP kinase were activated by BDNF. BDNF also increased c-fos expression in over 90% of the cells. These results indicate that gp145trkB does not require p75LNGFR to form a functional receptor for BDNF in hippocampal pyramidal neurons.

Journal ArticleDOI
TL;DR: Nuclear sclerosis and posterior subcapsular opacity were significantly associated with CAT scans, and the importance of minimizing such exposure to the lens of the eye was highlighted.
Abstract: The Beaver Dam Eye Study is a population-based study of common age-related eye diseases. During the standardized medical history, the 4926 subjects were asked whether they had ever had a chest x-ray, computerized axial tomography (CAT) scan of the head, other x-rays of the head, x-rays of the abdomen, or other diagnostic x-rays. The eye examination included photographs of the lenses of the eyes, which were subsequently graded according to protocol. Nuclear sclerosis and posterior subcapsular opacity were significantly associated with CAT scans. If these relationships are causal, it would highlight the importance of minimizing such exposure to the lens of the eye.

Journal Article
TL;DR: There is no evidence of a relationship between open-angle glaucoma and migraine headache in this population-based study.
Abstract: PURPOSE To investigate the relationship of a history of migraine headache to open-angle glaucoma. METHODS In an epidemiologic study of age-related eye disease, subjects were asked if they had migraine headaches. The diagnosis of glaucoma was based on visual field, intraocular pressure, cup/disc ratio, and history. RESULTS Those younger than 65 years were significantly more likely to report a history of migraine (P = 0.001) as were women (P < 0.001). There was no difference in the frequency of open-angle glaucoma between those with and those without migraine headache (P = 0.87). Multivariate analyses did not alter the conclusion. CONCLUSION In this population-based study there is no evidence of a relationship between open-angle glaucoma and migraine headache.

Journal ArticleDOI
TL;DR: It is suggested that gross proteinuria is a risk indicator for proliferative retinopathy in younger-onset patients with diabetes and these patients might benefit from having regular ophthalmologic evaluation.

Journal ArticleDOI
TL;DR: The relationship between alcohol use and lens opacities was examined in a large population-based study of adults aged 43 to 86 years in Beaver Dam, Wis and found a history of heavy drinking was related to more severe nuclear sclerotic, cortical, and posterior subcapsular opacITIES.
Abstract: • The relationship between alcohol use and lens opacities was examined in a large (N=4926) population-based study of adults aged 43 to 86 years in Beaver Dam, Wis. These data were collected from 1988 to 1990. Alcohol history was determined by a standardized questionnaire. Prevalence and severity of cataract were determined by masked grading of photographs obtained using a slit-lamp camera and retroillumination. A history of heavy drinking was related to more severe nuclear sclerotic, cortical, and posterior subcapsular opacities (odds ratios, 1.34, 1.38, and 1.57, respectively). These relationships remained after adjusting for other risk factors such as smoking. Moderate liquor consumption was associated with less severe nuclear sclerosis (odds ratio, 0.81). Participants who drank wine had less severe nuclear sclerosis (odds ratio, 0.84) and cortical opacities (odds ratio, 0.84) than those who did not. Increased consumption of beer was related to increased risk of cortical opacities.

Journal ArticleDOI
01 Mar 1993-Diabetes
TL;DR: The data suggest that smoking and glycemic control, both potentially modifiable factors, are significant risk factors for the development of gross proteinuria.
Abstract: A few population-based studies describe the incidence of gross proteinuria in people with diabetes. We performed a population-based study in southern Wisconsin of diabetic individuals diagnosed at > or = 30 yr of age either taking insulin (n = 398) or not taking insulin (n = 441). The presence of gross proteinuria (> or = 0.3 g/L) was determined by means of a reagent strip. The incidence of proteinuria in the 4-yr interval was 17.3% (95% CI 13.6-21.0) in those taking insulin and 10.7% (95% CI 7.8-13.6) in those not taking insulin. The relative risk of developing proteinuria for those in the highest level of total pack-yr smoked compared with those who had never smoked was 2.0 (95% CI 1.2-3.3) for those taking insulin and 2.5 (95% CI 1.3-4.5) for those not taking insulin. After controlling for other risk variables, the incidence of gross proteinuria was also associated with higher GHb. These data suggest that smoking and glycemic control, both potentially modifiable factors, are significant risk factors for the development of gross proteinuria.

Journal ArticleDOI
TL;DR: In people with diabetes, no significant associations were observed between GHb and intake of vitamins E and C and beta-carotene and in people without diabetes, energy-adjusted vitamin C intake was negatively associated with GHb after age and sex were controlled for.

Journal ArticleDOI
TL;DR: HbA1, an integrated measure of blood glucose concentration over a period of 2–3 months, is slightly more closely associated with the prevalence and incidence of diabetic retinopathy than a single blood glucose determination.
Abstract: Among Pima Indians with Type 2 (non-insulin-dependent) diabetes mellitus the relationships between glycated haemoglobin (HbA1), fasting or 2-h post-load plasma glucose and diabetic retinopathy were examined by cross-sectional and prospective analyses, and the strengths of the associations were directly compared by receiver operating characteristic analysis In the cross-sectional analysis, HbA1, fasting and 2-h plasma glucose were each significantly related to retinopathy among 789 diabetic subjects by separate logistic models In a stepwise multiple logistic model in which HbA1, fasting and 2-h plasma glucose were included, HbA1 was selected as having the strongest association with retinopathy and neither fasting nor 2-h plasma glucose contributed significantly to the model once HbA1 was entered Similarly, in the prospective analysis, HbA1, fasting and 2-h plasma glucose all predicted retinopathy in 227 diabetic subjects by separate proportional-hazards models In a stepwise proportional-hazards model with HbA1, fasting and 2-h plasma glucose available to the model, HbA1 was again selected as having the strongest association with the incidence of retinopathy, and neither fasting nor 2-h plasma glucose significantly added to the prediction of retinopathy A receiver operating characteristic analysis was used to determine if HbA1 was statistically significantly better than fasting or 2-h plasma glucose in assessing the risk for retinopathy In neither the cross-sectional nor the prospective data did the area under the receiver operating characteristic curve for HbA1 differ significantly from that for fasting or 2-h plasma glucose (p>005 for each) In conclusion, HbA1, an integrated measure of blood glucose concentration over a period of 2–3 months, is slightly more closely associated with the prevalence and incidence of diabetic retinopathy than a single blood glucose determination However, the differences between HbA1 and fasting or 2-h plasma glucose in assessing the association with or the risk for retinopathy are not significant

Journal Article
TL;DR: Estimates of the prevalence of retinal lesions in nondiabetic persons with and without hypertension suggest that retinopathy, and retinal arteriolar narrowing, are common.
Abstract: This study provides precise estimates of the prevalence of retinal lesions in nondiabetic persons with and without hypertension. The findings suggest that retinopathy (6% in normotensives and 11% in people with hypertension), and retinal arteriolar narrowing (11% in normotensives and 19% in people with hypertension) are common. Further longitudinal study is necessary to evaluate the public health significance of these findings.

Journal ArticleDOI
TL;DR: The effect of risk factors for retinopathy was similar in both ethnic groups, and longer duration of diabetes, more severe glycemia, earlier age at diagnosis, and insulin therapy were associated with diabetic Retinopathy in both Mexican Americans and Caucasians.

Journal ArticleDOI
TL;DR: Regular use of supplements was most prevalent among older men and women and the impact of supplement intake on median values of intake was greatest in women, particularly for vitamins A, C and E, riboflavin and calcium.
Abstract: Intake of macronutrients and micronutrients was estimated from a diet history questionnaire in a population-based sample of persons (n = 2152), 43-86 y of age. Men and women 65 y of age or older consumed less protein, fat, cholesterol, niacin, riboflavin, calcium, iron, zinc and lycopene than their middle-aged counterparts. After including nutrient intake from supplements, age differences in intake were no longer significant for zinc in women or for niacin and iron in men. After further adjusting for energy intake, only protein, cholesterol, and lycopene mean intakes were lower in older compared with middle-aged men and women. Regular use of supplements was most prevalent among older men and women (40 and 48%, respectively). Supplement use was greater in the current time period compared with retrospective reports of supplement use 10 y before interview. The impact of supplement intake on median values of intake was greatest in women, particularly for vitamins A, C and E, riboflavin and calcium. The high prevalence of supplement use emphasizes the importance of considering this source of nutrients in future investigations in which dietary intake is measured.

Proceedings Article
29 Nov 1993
TL;DR: The use of smoothing spline analysis of variance (SSANOVA) in the penalized log likelihood context, for learning (estimating) the probability p of a '1' outcome, given a training set with attribute vectors and outcomes is described.
Abstract: We describe the use of smoothing spline analysis of variance (SSANOVA) in the penalized log likelihood context, for learning (estimating) the probability p of a '1' outcome, given a training set with attribute vectors and outcomes. p is of the form p(t) = ef(t)/(1 + ef(t)), where, if t is a vector of attributes, f is learned as a sum of smooth functions of one attribute plus a sum of smooth functions of two attributes, etc. The smoothing parameters governing f are obtained by an iterative unbiased risk or iterative GCV method. Confidence intervals for these estimates are available.

Journal ArticleDOI
TL;DR: The relationship to low-serum sex hormone-binding globulin suggests that increased androgenicity may be associated with the progression of retinopathy in male subjects with type I diabetes.

Journal ArticleDOI
TL;DR: 45 degrees nonstereoscopic fundus photographs, when graded according to a standard classification scheme, should be considered for detection of age-related maculopathy in situations where the pupils cannot be pharmacologically dilated and retinal specialists are not available to examine the fundus.
Abstract: Purpose: The study was designed to compare the severity of age-related maculopathy as graded from photographs taken using three different techniques. Methods: Two methods of nonstereoscopic 45° retinal photography of the macula (through a nonpharmacologically dilated pupil and through a pharmacologically dilated pupil) were compared with results from standard 30° stereoscopic photographs in 112 subjects. Corresponding photographic fields were graded by a masked grader for the presence of any drusen, soft drusen, retinal pigment epithelial degeneration, increased retinal pigmentation, and early and late age-related maculopathy. Results: Exact agreement between gradings of the 45° photographs taken through nonpharmacologically dilated pupils and 30° photographs taken through dilated pupils was 75% for any drusen, 72% for soft drusen, 72% for retinal pigment epithelial degeneration, 74% for increased retinal pigment, 85% for pure geographic atrophy, and 89% for exudative macular degeneration. The kappa scores varied from 0.33 for geographic atrophy to 0.60 for exudative macular degeneration. Slightly higher rates of agreement between gradings were found after dilation. Conclusion: These data suggest that 45° nonstereoscopic fundus photographs, when graded according to a standard classification scheme, should be considered for detection of age-related maculopathy in situations where the pupils cannot be pharmacologically dilated and retinal specialists are not available to examine the fundus.

Journal ArticleDOI
TL;DR: It is suggested that exudative macular degeneration is associated with cigarette smoking and that different forms of maculopathy may have different etiologies.
Abstract: There are conflicting reports regarding the relation of cigarette smoking to age-related maculopathy, a major cause of blindness in the United States. In this report, the authors examined this association in people aged 43-86 years (n = 4,771) who participated in the Beaver Dam Eye Study, Beaver Dam, Wisconsin (1988-1990). Exposure data on cigarette smoking were derived from questions about present and past smoking, duration of smoking, and the number of cigarettes smoked per day. Age-related maculopathy status was determined by grading stereoscopic color fundus photographs using the Wisconsin Age-related Maculopathy Grading System. Smoking status, pack-years smoked, and current exposure to passive smoking were not associated with drusen characteristics (type, area, and confluence) or signs of early age-related maculopathy in any age-sex group studied, except for a higher frequency of increased retinal pigment in males who had ever smoked compared with those who had never smoked. The relative odds for exudative macular degeneration, one form of late age-related maculopathy, in females who were current smokers was 2.50 (95% confidence interval 1.01-6.20) compared with those who were ex-smokers or never smokers; for males, it was 3.29 (95% confidence interval 1.03-10.50). There was no significant relation between smoking status and pure geographic atrophy, another form of late age-related maculopathy. These results suggest that exudative macular degeneration is associated with cigarette smoking and that different forms of macular degeneration may have different etiologies.