Refractive errors and 10-year incidence of age-related maculopathy.

PURPOSE: To describe the relationship of refractive errors to the 10-year incidence of age-related maculopathy (ARM) in a defined white population. METHODS: Persons aged 43 to 86 years of age in Beaver Dam, Wisconsin, were invited for a baseline examination from 1988 through 1990, and follow-up examinations 5 and 10 years later (n = 3684). Refraction was measured at baseline, with myopia defined as a spherical equivalent of -1.00 D or less, emmetropia as -0.75 to +0.75 D and hyperopia as +1.00 D or more. At each examination, signs of ARM were ascertained from grading stereoscopic color fundus photographs based on a standard protocol. The association between baseline refractive status and the 10-year incidence and progression of ARM was analyzed. RESULTS: The 10-year cumulative incidence for early ARM was 7.1%, 7.7%, and 11.7%, in eyes with myopia, emmetropia, and hyperopia, respectively. The corresponding 10-year cumulative incidence for late ARM was 0.3%, 0.8%, and 2.2%. When age was controlled for, there was no association between myopia and incident early (relative risk [RR] 1.0, 95% confidence interval [CI], 0.7-1.3) and late (RR 0.5, 95% CI, 0.2-1.5) ARM. Similarly, after controlling for age, hyperopia was not associated with incident early (RR 0.9, 95% CI, 0.7-1.1) or late (RR 1.2, 95% CI, 0.6-2.3) ARM. CONCLUSIONS: These prospective population-based data provide no evidence of an association between refractive errors and risk of ARM.

Location of lesions associated with age-related maculopathy over a 10-year period: the Beaver Dam Eye Study.

PURPOSE: To describe cumulative incidence and changes in retinal lesions associated with age-related maculopathy (ARM) by location over a 10-year period and to examine the relation of location of those lesions to progression of ARM. METHODS: Persons ranging in age from 43 to 84 years and living in Beaver Dam, Wisconsin, at the time of a census (1987-1988) were examined two to three times over a 10-year period (n = 3684). Drusen area, size, and type; retinal pigment epithelium depigmentation; increased pigment; geographic atrophy; and neovascular macular degeneration were determined in each of nine macular subfields: central, inner and outer superior, inner and outer nasal, inner and outer inferior, and inner and outer temporal by grading of stereoscopic color fundus photographs. Late ARM was defined as presence of either geographic atrophy or neovascular ARM. RESULTS: Lesions were more likely to change or develop in specific locations. Drusen area increased most in the central circle. Compared with other quadrants, drusen greater than 125 micro m in diameter and soft indistinct or reticular drusen were most likely to develop in the superior or temporal quadrants, whereas pigmentary abnormalities were most likely to occur in the nasal or superior quadrants. In general, large drusen, soft indistinct drusen, and pigmentary abnormalities were more likely to develop in the inner circle versus the central and outer circles. The quadrant location of early ARM lesions in 72 persons in whom late ARM developed was generally similar to that in persons who did not have late ARM. However, persons who had geographic atrophy were more likely to have large drusen in the inner circle than in the outer circle, while those who did not have late ARM were more likely to have large drusen in the outer circle. CONCLUSIONS: Lesions associated with early ARM were more likely to develop in specific locations in the macular area, and persons with lesions closer to the fovea may be related to a higher risk of development of late ARM. The quadrant location of early ARM lesions does not appear to add additional information to the risk of development of late ARM.

Association of emphysema, gout, and inflammatory markers with long-term incidence of age-related maculopathy.

OBJECTIVE: To examine the relationship of 2 diseases associated with systemic inflammatory response, emphysema and gout, and selected markers of systemic inflammation with the 10-year incidence of age-related maculopathy. DESIGN: Population-based cohort study. PARTICIPANTS: We included persons aged 43 to 86 years at baseline examination from 1988 to 1990 living in Beaver Dam, Wis, of whom 3684 subjects participated in a 5-year follow-up examination and 2764 participated in a 10-year follow-up. METHODS: Standardized protocols for physical examination, blood collection, administration of a questionnaire, and stereoscopic color fundus photography to determine the presence of age-related maculopathy. Standard univariate and multivariate analyses were performed. MAIN OUTCOME MEASURES: Incidence and progression of age-related maculopathy. RESULTS: While controlling for age, sex, and other factors (history of heavy drinking or smoking, systolic blood pressure, and vitamin use), a higher white blood cell count at baseline was associated with the 10-year incidence of drusen 125 microm or greater in diameter (risk ratio [RR] per 10(6)/ microL = 1.10; 95% confidence interval [CI], 1.03-1.17), retinal pigment epithelial depigmentation (RR = 2.08; 95% CI, 1.01-1.16), and progression of age-related maculopathy (RR = 1.09; 95% CI, 1.03-1.15). A lower serum albumin level was associated with the incidence of exudative macular degeneration (RR per grams per deciliter = 0.31; 95% CI, 0.13-0.76). A history of emphysema at baseline was associated with the incidence of retinal pigment epithelial depigmentation (RR = 2.84; 95% CI, 1.40-5.78), increased retinal pigment (RR = 2.20; 95% CI, 1.11-4.35), and exudative macular degeneration (RR = 5.12; 95% CI, 1.63-16.06); a history of gout was associated with the incidence of pure geographic atrophy (RR = 3.48; 95% CI, 1.27-9.53). CONCLUSIONS: These findings indicate modest relationships between both increased white blood cell count and emphysema and the increased 10-year incidence of lesions defining early and late age-related maculopathy. Further investigation of these relationships in other studies is needed.

Sunlight and the 10-year incidence of age-related maculopathy: the Beaver Dam Eye Study.

OBJECTIVE: To examine the association of sunlight exposure and indicators of sun sensitivity with the 10-year incidence of age-related maculopathy (ARM). DESIGN: Population-based cohort study. PARTICIPANTS: We included persons aged 43 to 86 years at the baseline examination from 1988 to 1990, living in Beaver Dam, Wis, of whom 3684 persons underwent 5-year follow-up and 2764 underwent 10-year follow-up. METHODS: Data on sun exposure and indicators of sun sensitivity were obtained from a standardized questionnaire administered at baseline and/or follow-up. We determined ARM status by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Incidence and progression of ARM. RESULTS: While controlling for age and sex, we found that participants exposed to the summer sun for more than 5 hours a day during their teens, in their 30s, and at the baseline examination were at a higher risk of developing increased retinal pigment (risk ratio [RR], 2.99; 95% confidence interval [CI], 1.18-7.60; P =.02) and early ARM (RR, 2.20; 95% CI, 1.02-4.73; P =.04) [corrected] by 10 years than those exposed less than 2 hours per day during the same periods. In participants reporting the highest summer sun exposure levels in their teens and 30s, the use of hats and sunglasses at least half the time during the same periods was associated with a decreased risk of developing soft indistinct drusen (RR, 0.55; 95% CI, 0.33-0.90; P =.02) and retinal pigment epithelial depigmentation (RR, 0.51; 95% CI, 0.29-0.91; P =.02). Participants who experienced more than 10 severe sunburns during their youth were more likely than those who experienced 1 or no burn to develop drusen with a 250-microm diameter or larger (RR, 2.52; 95% CI, 1.29-4.94 [corrected] P =.01) by the 10-year examination. No relationships were found between UV-B exposure, winter leisure time spent outdoors, skin sun sensitivity, or number of bad sunburns experienced by the time of the baseline examination and the 10-year incidence and progression of ARM or its associated lesions. CONCLUSIONS: Few significant relationships between environmental exposure to light and the 10-year incidence and progression of ARM were found in the Beaver Dam Eye Study. Consistent with results from the baseline and 5-year follow-up examinations, significant associations were found between extended exposure to the summer sun and the 10-year incidence of early ARM and increased retinal pigment. A protective effect of hat and sunglasses use by participants while in their teens and 30s against the 10-year incidence of soft indistinct drusen and retinal pigment epithelial depigmentation was also found, but only in those who reported the highest amount of sun exposure during the same periods.

Relation of statin use to the 5-year incidence and progression of age-related maculopathy.

OBJECTIVE: To examine the association of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) with the 5-year incidence of age-related maculopathy (ARM). DESIGN: Population-based cohort study. Participants included persons 48 to 91 years old examined March 1, 1993, through June 14, 1995, living in Beaver Dam, Wis (N = 3684), of whom 2780 participated in a follow-up 5 years later. METHODS: Standardized procedures were used for physical examinations, blood sample collection, and questionnaire administration. Age-related maculopathy was determined by grading images of the posterior pole using a standard protocol. Standard univariate and multivariate analyses were performed. MAIN OUTCOME MEASURES: Incidence and progression of ARM was measured over the 5-year interval. RESULTS: While controlling for age and sex, statin use was not found to be associated with the 5-year incidence of early ARM (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.47-2.67), progression of ARM (OR, 1.22; 95% CI, 0.54-2.76), or incidence of late ARM (OR, 0.41; 95% CI, 0.12-1.45). CONCLUSIONS: These findings do not suggest an association between statin use and incident ARM over a 5-year period. Further investigation of these relationships in larger studies over a longer period is needed.

The association of cataract and cataract surgery with the long-term incidence of age-related maculopathy: the Beaver Dam eye study.

OBJECTIVE: To examine the association between cataract and cataract surgery and the 10-year incidence of age-related maculopathy (ARM). METHODS: A population-based cohort study of persons aged 43 to 86 years at baseline, living in Beaver Dam, Wis, of whom 3684 participated in a 5-year and 2764 in a 10-year follow-up. We used standardized protocols for physical examination, blood collection, health history, slitlamp and retroillumination photography of the lenses to determine the presence of cataract, and stereoscopic color fundus photography to determine the presence of ARM. We used the Kaplan-Meier (product-limit) survival approach and discrete linear logistic regression in analyses. MAIN OUTCOME MEASURES: The risk ratios (RRs) of persons with cataract or cataract surgery at baseline. RESULTS: While controlling for age, sex, systolic blood pressure, history of heavy drinking and smoking, and vitamin use, cataract at baseline was associated with incidence of early ARM (RR, 1.30; 95% confidence interval [CI], 1.04-1.63), soft indistinct drusen (RR, 1.38; 95% CI, 1.08-1.75), increased retinal pigment (RR, 1.38; 95% CI, 1.07-1.79), and progression of ARM (RR, 1.37; 95% CI, 1.06-1.77). We found no association with the incidence of late ARM. In contrast, cataract surgery before baseline was associated with incidence of late ARM (RR, 3.81; 95% CI, 1.89-7.69), increased retinal pigment (RR, 1.89; 95% CI, 1.18-3.03), retinal pigment epithelial depigmentation (RR, 1.95; 95% CI, 1.17-3.25), pure geographic atrophy (RR, 3.18; 95% CI, 1.33-7.60), exudative macular degeneration (RR, 4.31; 95% CI, 1.71-10.9), and progression of ARM (RR, 1.97; 95% CI, 1.29-3.02), but not with the incidence of early ARM. CONCLUSIONS: These findings indicate an association of cataract with subsequent risk for early ARM. Cataract surgery increased the risk for late ARM.

Prevalence of age-related macular degeneration in the United States.

OBJECTIVE: To estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender. METHODS: Summary prevalence estimates of drusen 125 microm or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US Census data and to projected US population figures for 2020 to estimate the number of the US population with drusen and AMD. RESULTS: The overall prevalence of neovascular AMD and/or geographic atrophy in the US population 40 years and older is estimated to be 1.47% (95% confidence interval, 1.38%-1.55%), with 1.75 million citizens having AMD. The prevalence of AMD increased dramatically with age, with more than 15% of the white women older than 80 years having neovascular AMD and/or geographic atrophy. More than 7 million individuals had drusen measuring 125 microm or larger and were, therefore, at substantial risk of developing AMD. Owing to the rapidly aging population, the number of persons having AMD will increase by 50% to 2.95 million in 2020. Age-related macular degeneration was far more prevalent among white than among black persons. CONCLUSION: Age-related macular degeneration affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.

The relation of retinal microvascular characteristics to age-related eye disease: the Beaver Dam eye study.

PURPOSE: To examine the relationship between microvascular characteristics (central retinal artery equivalent [CRAE], central retinal vein equivalent [CRVE], arteriole-to-venule ratio [AVR], focal retinal arteriolar narrowing, arteriovenous [A/V] nicking, and retinopathy) associated with systemic hypertension and ocular disease (age-related maculopathy [ARM], three types of cataract, and open-angle glaucoma). DESIGN: Population-based cohort study. METHODS: Standardized grading of microvascular characteristics was performed at baseline on fundus photographs taken on 4,926 persons aged 43 to 86 years who participated in the Beaver Dam Eye study at the baseline examination. Age-related maculopathy, cataract, and glaucoma status were determined at baseline; ARM and cataract were again determined at 5-year and 10-year follow-up examinations using standard protocols. RESULTS: While controlling for age and sex, generalized retinal arteriolar narrowing (lowest quintile of CRAE) was associated with the 10-year cumulative incidence of retinal pigment epithelial (RPE) depigmentation (risk ratio [RR] 1st vs 5th quintile, 1.93; 95% confidence interval [CI], 1.11, 3.34) and, inversely, with incident nuclear cataract (RR, 0.71; 95% CI, 0.50, 0.99). Arteriovenous nicking was associated with the incidence of early ARM (RR, 2.39; 95% CI, 1.02, 5.57). Otherwise, there were no statistically significant associations of focal arteriolar narrowing or retinopathy with incident ARM or any type of age-related cataract and no relation of CRAE, focal arteriolar narrowing, A/V nicking, or retinopathy with the prevalence of glaucoma. CONCLUSION: These data show that retinal vascular characteristics associated with hypertension are related to the incidence of ARM and nuclear cataract but not to prevalent glaucoma. Relationships, however, were weak and inconsistent.

Urban parents' knowledge and practices regarding managed care.

BACKGROUND: Managed care is the dominant form of health insurance in the United States, covering millions of children. Little is known about whether inner-city parents adequately understand managed care's complex definitions and rules. OBJECTIVE: The objective of this study was to examine managed care knowledge and practices among inner-city parents. METHODS: We conducted a cross-sectional survey of parents at inner-city community sites in Boston, including supermarkets, hair salons, and laundromats. Participants were asked 74 questions on access, insurance, and managed care. RESULTS: The 1100 participants were mostly poor, minority (82% Latino, 10% black) and covered by public health insurance. Although 55% of insured children were covered by managed care, 45% of the managed care-covered children's parents were unaware of their children's managed care coverage. When asked "What is managed care?," 88% of parents did not know it was a type of insurance, and 94% did not identify a specific feature; Latino parents were significantly more likely to provide a wrong/do not know answer to this question, and there was no significant association with whether the child was covered by managed care. Latino parents and parents with children not covered by managed care were significantly more likely to provide a wrong/do not know answer for all 11 questions about specific features of managed care, but the proportion of parents with managed care-covered children who gave wrong/do not know answers for these 11 questions ranged from 41% to 84%. More than half of parents gave wrong/do not know answers to 10 of the 11 questions about specific managed care features, regardless of whether their child was covered by managed care. Most parents reported that if their child were covered by managed care, they would bring the child to the emergency department without prior approval for 4 minor childhood illnesses. For each of these illnesses, at least two thirds of parents said that they would bring their child in without prior approval, ranging from 72% of parents for a child with diarrhea to 90% for a child with a sprained ankle. Latino ethnicity (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.1), having a nonmanaged care-covered child (OR, 2.3; 95% CI, 1.5-3.7), and having a managed care-covered child but being unaware of the managed care coverage (OR, 2.9; 95% CI, 1.6-5.2) were associated with greater adjusted odds of incorrect/do not know parental definitions of managed care. Low family income and limited English proficiency were consistently associated with a significantly higher adjusted odds of wrong/do not know answers about specific managed care features. In multivariable analyses, Latino parents were significantly more likely to bring a managed care-covered child with a minor illness to the emergency department without prior approval. CONCLUSIONS: Regardless of whether their children have managed care coverage, most inner-city parents interviewed in this study do not know what managed care is, have insufficient knowledge of managed care rules and practices, and believe that prior approval for emergency department visits for mild childhood illnesses is unnecessary. These findings indicate that many urban parents may need better, more comprehensible information about managed care, particularly those who are poor, Latino, and have limited English proficiency.

The relationship between iris color, hair color, and skin sun sensitivity and the 10-year incidence of age-related maculopathy: the Beaver Dam Eye Study.

PURPOSE: To examine the association between iris color, hair color, and skin sun sensitivity and the 10-year incidence of age-related maculopathy (ARM). DESIGN: Population-based cohort study. PARTICIPANTS: A population of 4926 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied at baseline (1988-1990); of these, 3684 and 2764 subjects, respectively, participated in 5-year and 10-year follow-up examinations. METHODS: Data on hair color at age 15 years and skin responsiveness to sun exposure were obtained from a standardized questionnaire administered at the baseline examination. Iris color was determined with penlight illumination during the baseline examination by using photographic standards. Age-related maculopathy status was determined by grading stereoscopic color fundus photos with the Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Incidence and progression of ARM. RESULTS: When controlling for age and gender, people with brown eyes were significantly more likely to develop soft indistinct drusen (risk ratio [RR], 1.53; 95% confidence interval [CI], 1.19-1.97; P < 0.01) than were people with blue eyes. However, people with brown eyes were significantly less likely to develop retinal pigment epithelial depigmentation (RR, 0.58; 95% CI, 0.41-0.82; P < 0.01) than were people with blue eyes. When compared with persons with blond hair, persons with brown hair were at decreased risk of developing pigmentary abnormalities (RR, 0.73; 95% CI, 0.53-1.00; P = 0.05). Iris color, hair color, and skin sun sensitivity were not associated with the development of late ARM. CONCLUSION: Iris color and hair color were found to be associated with the 10-year incidence of pigmentary abnormalities. Iris color seems to be inconsistently related to the 10-year incidence of early ARM lesions and the progression of ARM.

The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam eye study.

PURPOSE: To examine the association between cardiovascular disease and its risk factors and the 10-year incidence of age-related maculopathy. DESIGN: Population-based cohort study. PARTICIPANTS: Persons 43 to 86 years of age at baseline examination from 1988 to 1990, living in Beaver Dam, Wisconsin, of whom 3684 persons participated in a 5-year follow-up examination and 2764 participated in a 10-year follow-up examination. METHODS: Standardized protocols for physical examination, blood collection, administration of a questionnaire, and stereoscopic color fundus photography to determine age-related maculopathy. The Kaplan-Meier (product-limit) survival approach and discrete linear logistic regression were used in the data analysis. MAIN OUTCOME MEASURES: Incidence and progression of age-related maculopathy. RESULTS: When age, gender, and history of heavy drinking, smoking, and vitamin use were controlled for, higher systolic blood pressure at baseline was associated with the 10-year incidence of retinal pigment epithelial depigmentation (risk ratio [RR] per 10 mmHg systolic blood pressure, 1.10; 95% confidence interval [CI], 1.01-1.18; P = 0.02) and exudative macular degeneration (RR, 1.22; 95% CI, 1.06-1.41; P = 0.006). Higher pulse pressure at baseline was associated with the incidence of retinal pigment epithelial depigmentation (RR per 10 mmHg, 1.17; 95% CI, 1.07-1.28; P < 0.001), increased retinal pigment (RR, 1.10; 95% CI, 1.01-1.19; P = 0.03), exudative macular degeneration (RR, 1.34; 95% CI, 1.14-1.60; P < 0.001), and progression of age-related maculopathy (RR, 1.08; 95% CI, 1.01-1.17; P = 0.03). Higher serum high-density lipoprotein cholesterol at baseline was associated with pure geographic atrophy (RR per 10 mg/dl high-density lipoprotein cholesterol, 1.29; 95% CI, 1.05-1.58; P = 0.01). Physical activity at baseline was associated with the incidence of geographic atrophy (RR in those who worked up a sweat 5 times a week compared with those who did not, 0.12; 95% CI, 0.02-0.91; P = 0.04) exudative macular degeneration (RR, 0.27; 95% CI, 0.08-0.87; P = 0.05), and progression of age-related maculopathy (RR, 0.69; 95% CI, 0.47-1.00; P = 0.05). Neither a history of stroke nor heart attack was associated with the incidence or progression of age-related maculopathy. CONCLUSIONS: These findings indicate relationships between higher pulse pressure (a presumed indicator of age-related elastin and collagen changes in Bruch's membrane) and systolic blood pressure with an increased 10-year incidence of some lesions defining early age-related maculopathy and exudative macular degeneration.

Birth cohort effect on prevalence of age-related maculopathy in the Beaver Dam Eye Study.

The number of people in the United States with age-related maculopathy is increasing in recent years because of increasing longevity. However, it is possible that a birth cohort effect, due to different levels of exposure to risk factors, may explain changes in the prevalence of age-related maculopathy by age. In this report, the authors utilize data from the population-based Beaver Dam Eye Study (1988-2000) to examine this possibility. They propose a strategy to handle issues of longitudinal measurements and risk factor adjustment for analyzing the birth cohort effect. Results from the analysis (after adjusting for known risk factors) showed an apparent independent birth cohort effect on age-related maculopathy. The authors also found a strong positive association between age-related maculopathy and age, when comparing participants from the same birth cohort. The birth cohort effect was the same across different age groups, except for early age-related maculopathy, where older age increased the association. Our findings demonstrate that the birth cohort effect is likely attributable to unmeasured risk factors for age-related maculopathy and limitations of risk factor measurements. Further study of possible unmeasured risk factors that cause the cohort effect may help us understand the etiology of the disease.

The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam Eye Study.

PURPOSE: To examine the association between cardiovascular disease and its risk factors and the 10-year incidence of age-related maculopathy. DESIGN: Population-based cohort study. PARTICIPANTS: Persons 43 to 86 years of age at baseline examination from 1988 to 1990, living in Beaver Dam, Wisconsin, of whom 3684 persons participated in a 5-year follow-up examination and 2764 participated in a 10-year follow-up examination. METHODS: Standardized protocols for physical examination, blood collection, administration of a questionnaire, and stereoscopic color fundus photography to determine age-related maculopathy. The Kaplan-Meier (product-limit) survival approach and discrete linear logistic regression were used in the data analysis. MAIN OUTCOME MEASURES: Incidence and progression of age-related maculopathy. RESULTS: When age, gender, and history of heavy drinking, smoking, and vitamin use were controlled for, higher systolic blood pressure at baseline was associated with the 10-year incidence of retinal pigment epithelial depigmentation (risk ratio [RR] per 10 mmHg systolic blood pressure, 1.10; 95% confidence interval [CI], 1.01-1.18; P = 0.02) and exudative macular degeneration (RR, 1.22; 95% CI, 1.06-1.41; P = 0.006). Higher pulse pressure at baseline was associated with the incidence of retinal pigment epithelial depigmentation (RR per 10 mmHg, 1.17; 95% CI, 1.07-1.28; P < 0.001), increased retinal pigment (RR, 1.10; 95% CI, 1.01-1.19; P = 0.03), exudative macular degeneration (RR, 1.34; 95% CI, 1.14-1.60; P < 0.001), and progression of age-related maculopathy (RR, 1.08; 95% CI, 1.01-1.17; P = 0.03). Higher serum high-density lipoprotein cholesterol at baseline was associated with pure geographic atrophy (RR per 10 mg/dl high-density lipoprotein cholesterol, 1.29; 95% CI, 1.05-1.58; P = 0.01). Physical activity at baseline was associated with the incidence of geographic atrophy (RR in those who worked up a sweat 5 times a week compared with those who did not, 0.12; 95% CI, 0.02-0.91; P = 0.04) exudative macular degeneration (RR, 0.27; 95% CI, 0.08-0.87; P = 0.05), and progression of age-related maculopathy (RR, 0.69; 95% CI, 0.47-1.00; P = 0.05). Neither a history of stroke nor heart attack was associated with the incidence or progression of age-related maculopathy. CONCLUSIONS: These findings indicate relationships between higher pulse pressure (a presumed indicator of age-related elastin and collagen changes in Bruch's membrane) and systolic blood pressure with an increased 10-year incidence of some lesions defining early age-related maculopathy and exudative macular degeneration.

Ten-year incidence of age-related maculopathy and smoking and drinking: the Beaver Dam Eye Study.

The authors examined associations between smoking and alcohol consumption and the long-term incidence of age-related maculopathy (ARM) in people in the Beaver Dam Eye Study who were aged 43-86 years (n = 3,684) in 1988-1990 and examined over a 10-year period. ARM status was determined by grading stereoscopic color fundus photographs. After controlling for age, sex, and other factors, the authors found that people who had smoked more were more likely to develop large (> or =250 micro m in diameter) soft drusen (risk ratio (RR) per 10 pack-years smoked = 1.08, 95% confidence interval (CI): 1.02, 1.14) and pigmentary abnormalities (RR = 1.09, 95% CI: 1.04, 1.14) and to have progression of early ARM (RR = 1.05, 95% CI: 1.00, 1.10) than people who had smoked less. Smoking was not associated with the incidence of late ARM. People who reported being heavy drinkers at baseline were more likely to develop late ARM (RR = 6.94, 95% CI: 1.85, 26.1) than people who reported never having been heavy drinkers. Smoking appears to have a modest, positive association with early but not late signs of ARM, and heavy drinking appears to be related to an increased risk of late ARM, although the exposure and outcome were infrequent, and the effect is based on few exposed cases.

Ten-year incidence and progression of age-related maculopathy: The Beaver Dam eye study.

PURPOSE: The aim of the study was to describe the 10-year incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy. DESIGN: Population-based cohort study. PARTICIPANTS: The study included 4926 persons, 43 to 86 years of age at the time of a baseline examination from 1988 through 1990, living in Beaver Dam, Wisconsin, of whom 3684 participated in a 5-year follow-up examination and 2764 participated in a 10-year follow-up. METHODS: Characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOMES MEASURES: Incidence of drusen type and size, pigmentary abnormalities, geographic atrophy, and exudative degeneration. RESULTS: The 10-year incidence of early age-related maculopathy was 12.1% and of late age-related maculopathy it was 2.1%. There was a statistically significant increased incidence of age-related maculopathy lesions with age (P < 0.05). Individuals 75 years of age or older at baseline had significantly (P < 0.01) higher 10-year incidences of the following characteristics than people 43 to 54 years of age: larger sized drusen (125 micro m-249 micro m, 26.3% vs. 3.3%; > or =250 micro m, 16.2% vs. 1.0%), soft indistinct drusen (22.2% vs. 2.2%), retinal pigment abnormalities (19.5% vs. 0.8%), exudative macular degeneration (4.1% vs. 0%), and pure geographic atrophy (3.1% vs. 0%). Compared with those with small numbers of only small, hard drusen (1-2), those with large numbers of only hard drusen (8 or more) had an increased 10-year incidence of both soft drusen (12.3% vs. 6.7%) and pigmentary abnormalities (4.9% vs. 1.7%). Eyes with soft indistinct drusen or retinal pigmentary abnormalities at baseline, were more likely to develop late age-related macular degeneration at follow-up than eyes without these lesions (15.1% vs. 0.4% and 20.0% vs. 0.8%, respectively). CONCLUSIONS: These population-based estimates document the high incidence of signs of age-related maculopathy in people 75 years of age or older. Our findings demonstrate that large numbers of hard drusen predict the incidence of soft drusen and pigmentary abnormalities and that the presence of the latter lesions significantly increases the risk for the development of geographic atrophy and exudative macular degeneration.

Risk factors for incident age-related macular degeneration: pooled findings from 3 continents.

OBJECTIVE: To examine risk factors for incident age-related macular degeneration (AMD) after combining data from 3 population-based cohort studies. DESIGN: Population-based cohort study. POPULATION: A population of 9523 adults (age range, 43-95 years at baseline) living in Australia, The Netherlands, and the United States who participated in a baseline examination and a follow-up examination on average 5 or 6 years later. METHODS: Similar procedures were used at all study sites. Examinations included a standardized questionnaire, pupillary dilation, and stereoscopic color fundus photography. Fundus photographs were graded for lesions associated with AMD using the Wisconsin and International Age-Related Maculopathy Grading Systems. Senior investigators from each site adjudicated all photos graded as late AMD. MAIN OUTCOMES MEASURE: Incidence of late AMD. RESULTS: Among studies, distributions for most risk factors differed, and overall incidence rates were similar. In the Beaver Dam Eye Study, total serum cholesterol was inversely associated with incident neovascular AMD. In the Blue Mountains Eye Study, current smoking (defined as smoking at the time of the baseline examination) was associated with an increased risk of incident geographic atrophy and late AMD; increased total serum cholesterol, having diabetes, and older age at menopause were positively associated with incident geographic atrophy; and an increase in high-density lipoprotein serum cholesterol was inversely related to incident geographic atrophy. In the Rotterdam Study, current smoking was associated with an increased risk of incident geographic atrophy, neovascular AMD, and late AMD; past smoking was associated with an increased risk of incident neovascular AMD and late AMD; and an increased number of years between menarche and menopause was directly related to incident geographic atrophy. After pooling data, the only statistically significant relationships found were between smoking and total serum cholesterol and incident AMD. Current smoking was associated with an increased incidence of geographic atrophy and late AMD (odds ratios [ORs] relative to nonsmokers: 2.83 and 2.35, respectively; ORs relative to past smokers: 2.80 and 1.82, respectively), and total serum cholesterol was associated directly with incident geographic atrophy (OR: 1.08 per 10 mg/dl) and inversely with incident neovascular AMD (OR: 0.94 per 10 mg/dl). CONCLUSIONS: Pooled data support a growing body of evidence indicating that smoking is related to an increased risk of incident AMD. Current smokers were at higher risk of incident AMD than both past smokers and those who never smoked. The relationships found in this study between total serum cholesterol and incident geographic atrophy and neovascular AMD are not readily explained.

Is medication use associated with the incidence of early age-related maculopathy? Pooled findings from 3 continents.

OBJECTIVE: To investigate whether there is an association between the use of medication and the incidence of early age-related maculopathy (ARM). DESIGN: Pooled data from 3 prospective, population-based cohort studies. PARTICIPANTS: Subjects without early and late ARM at baseline who participated in the follow-up of the Beaver Dam Eye Study (n = 3012), the Rotterdam Study (n = 3434), and the Blue Mountains Eye Study (n = 2203). METHODS: Stereoscopic color fundus photographs of all participants were graded according to a standardized protocol. At baseline, current use of prescription and over-the-counter medication was assessed by interview, and the drug name was confirmed at the research centers. Procedures and definitions were similar at both baseline and follow-up across the 3 study sites. MAIN OUTCOME MEASURES: Incidence of early ARM, defined as the presence at follow-up of either soft distinct drusen with pigmentary changes or soft indistinct or reticular drusen. RESULTS: In the pooled cohort, 53.3% of participants used at least one of the medications selected for this study. Within a mean period of 5.6 years, a total of 683 subjects developed early ARM. Users of antihypertensive medication in general, and beta-blockers in particular, had a borderline statistically significant increased risk of early ARM (odds ratio [OR] for beta-blockers, 1.3; 95% confidence interval [CI], 1.0-1.6) when adjusted for systolic (or diastolic) blood pressure and other confounders. A protective effect of borderline significance was found among women using hormone replacement therapy (OR, 0.6; 95% CI, 0.4-1.0) and in persons using tricyclic antidepressants (OR, 0.4; 95% CI, 0.2-1.0). In contrast with beta-blockers, the direction and magnitude of the association with hormone replacement therapy and tricyclic antidepressants were inconsistent among the 3 study populations. CONCLUSIONS: Pooled data from 3 population-based studies showed no strong associations between medication use and the incidence of early ARM. Of borderline significance were a slightly increased risk among users of beta-blockers and a reduced risk among users of hormone replacement therapy and users of tricyclic antidepressants. Although beta-blocker use could be a proxy for systemic hypertension, these findings warrant further investigations, preferably including information on the dosage and duration of drug exposure.

A whole-genome screen of a quantitative trait of age-related maculopathy in sibships from the Beaver Dam Eye Study.

Age-related maculopathy (ARM) is a leading cause of visual impairment among the elderly in Western populations. To identify ARM-susceptibility loci, we genotyped a subset of subjects from the Beaver Dam (WI) Eye Study and performed a model-free genomewide linkage analysis for markers linked to a quantitative measure of ARM. We initially genotyped 345 autosomal markers in 325 individuals (N=263 sib pairs) from 102 pedigrees. Ten regions suggestive of linkage with ARM were observed on chromosomes 3, 5, 6, 12, 15, and 16. Prior to fine mapping, the most significant regions were an 18-cM region on chromosome 12, near D12S1300 (P=.0159); a region on chromosome 3, near D3S1763, with a P value of.0062; and a 6-cM region on chromosome 16, near D16S769, with a P value of.0086. After expanding our analysis to include 25 additional fine-mapping markers, we found that a 14-cM region on chromosome 12, near D12S346 (located at 106.89 cM), showed the strongest indication of linkage, with a P value of.004. Three other regions, on chromosomes 5, 6, and 15, that were nominally significant at P< or =.01 are also appropriate for fine mapping.