Stacy M. Meuer

The Five-year Incidence and Progression of Age-related Maculopathy

PURPOSE The aim of the study was to describe the incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy. POPULATION A population of 3583 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied during a 5-year period. 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. RESULTS There was a statistically significant increased incidence of age-related maculopathy lesions with age (P < 0.05). Individuals 75 years of age or older had a significantly (P < 0.01) higher 5-year incidence of the following characteristics than people 43 to 54 years of age: larger sized drusen (125-249 microm, 17.6% vs. 2.1%; > or = 250 microm, 6.5% vs. 0.2%), soft indistinct drusen (16.3% vs. 1.8%), retinal pigment abnormalities (12.9% vs. 0.9%), exudative macular degeneration (1.8% vs. 0%), and pure geographic atrophy (1.7% vs. 0%). After adjusting for age, the incidence of early age-related maculopathy was 2.2 times (95% confidence interval 1.6, 3.2) as likely in women 75 years of age or older compared with men this age. At follow-up, late age-related macular degeneration was more likely to develop in eyes with soft indistinct drusen (6.5% vs. 0.1%) or retinal pigmentary abnormalities (7.1% vs. 0.1%) at baseline than in eyes without these lesions. CONCLUSIONS These population-based estimates document the high incidence of signs of age-related maculopathy in people 75 years of age or older, and in women compared with men that age. The findings demonstrate that the presence of soft drusen and pigmentary abnormalities significantly increases the risk for the development of geographic atrophy and exudative macular degeneration.

Prevalence of Age-Related Macular Degeneration in the US Population

OBJECTIVE To examine the prevalence of age-related macular degeneration (AMD) in non-Hispanic white, non-Hispanic black, Mexican American, and other racial/ethnic groups. DESIGN A US nationally representative, population-based, cross-sectional study involving a total of 5553 persons aged 40 years and older from the 2005-2008 National Health and Nutrition Examination Survey. The main outcome measure was AMD determined by the grading of 45° digital images from both eyes using a standardized protocol. RESULTS In the civilian, noninstitutionalized, US population aged 40 years and older, the estimated prevalence of any AMD was 6.5% (95% confidence interval, 5.5-7.6) and the estimated prevalence of late AMD was 0.8% (95% confidence interval, 0.5-1.3). Non-Hispanic black persons aged 60 years and older had a statistically significantly lower prevalence of any AMD than non-Hispanic white persons aged 60 years and older (odds ratio = 0.37; 95% confidence interval, 0.21-0.67). CONCLUSIONS Overall, the prevalence of any AMD in the 2005-2008 National Health and Nutrition Examination Survey was 6.5%, which is lower than the 9.4% prevalence reported in the 1988-1994 Third National Health and Nutrition Examination Survey. While this finding might be explained in part by possible methodological differences, these estimates are consistent with a decreasing incidence of AMD and suggest important public health care implications.

An Alternative Method of Grading Diabetic Retinopathy

The purpose of this report is to present a system for grading the severity of diabetic retinopathy that is a rapid, relatively inexpensive, and standardized alternative to the more detailed Early Treatment Diabetic Retinopathy Study (ETDRS) system; present data on its reproducibility; and compare it to the detailed ETDRS grading system. The alternative system was used to grade fundus photographs obtained during a large prevalence study, the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). The alternative method involved grading seven stereoscopic standard fields as a whole, and assigning a level of severity for the eye according to the greatest degree of retinopathy using a modified Airlie House Classification scheme. Using an eight-level classification system of increasing severity of retinopathy, there was 78.3% exact agreement between the alternative and ETDRS systems. A grader regraded all 503 disagreements, and was in exact agreement 49.3% of the time with the alternative system, 35.7% of the time with the detailed system, and 15.0% with neither the alternative or detailed systems. Interobserver agreement for the alternative system was 78.5%; intraobserver agreement over a 9 month to 1 year period was 90.0% for grader 1 and 84.0% for grader 2. The alternative system of grading, when used by experienced graders, is a reproducible method for objectively determining retinopathy status in epidemiologic studies.

Retinal microvascular abnormalities and 10-year cardiovascular mortality: a population-based case-control study.

PURPOSE Retinal microvascular abnormalities reflect persistent arteriolar damage from hypertension and independently predict stroke. We examined their associations with long-term cardiovascular mortality. DESIGN Population-based, nested, case-control study. POPULATION Cases were Beaver Dam Eye Study participants (age range, 43-84 years) who died of coronary heart disease or stroke between the baseline examination in 1988 to 1990 and 1999 (n = 413). Nearly 3 controls per case were selected from the baseline cohort, frequency-matched on 5-year age intervals and gender (n = 1198). METHODS Retinal photographs of cases and controls at baseline were evaluated for retinopathy, focal arteriolar narrowing, and arteriovenous nicking by graders masked to case-control status using standardized protocols. To obtain an estimate of generalized arteriolar narrowing, photographs were digitized and diameters of individual retinal vessels were measured and summarized by a computer program. MAIN OUTCOME MEASURE Ten-year cardiovascular mortality. RESULTS After controlling for systolic blood pressure, diabetes, glycosylated hemoglobin levels, and other risk factors, retinopathy was associated with increased cardiovascular mortality, with odds ratios of 1.8 (95% confidence interval [CI], 1.2, 2.7). For other retinal abnormalities, associations with cardiovascular mortality were present only in younger people, with odds ratios of 2.7 (95% CI, 1.0, 7.4) for focal arteriolar narrowing, 1.8 (95% CI, 0.8, 4.5) for arteriovenous nicking, and 1.9 (95% CI, 1.2, 2.9) for generalized arteriolar narrowing in persons 43 to 74 years of age but odds ratios of 1.1, 0.4, and 1.0 for the corresponding retinal abnormalities in persons 75 years and older. CONCLUSIONS Retinopathy is independently associated with cardiovascular mortality. Associations for other retinal abnormalities were only observed in middle-aged persons. These data support recent studies that suggest retinal microvascular abnormalities provide independent information regarding cardiovascular risk.

The 15-Year Cumulative Incidence of Retinal Vein Occlusion: The Beaver Dam Eye Study

OBJECTIVES To describe the 15-year incidence of retinal vein occlusion (central retinal vein occlusion and branch retinal vein occlusion) and associated risk factors. METHODS A population-based study where branch retinal vein occlusion and central retinal vein occlusion were detected at baseline (n = 4068, 1988-1990) and three 5-year follow-up examinations by grading 30 degrees color fundus photographs. RESULTS The 15-year cumulative incidences of branch retinal vein occlusion and central retinal vein occlusion were 1.8% and 0.5%, respectively. Using a generalized estimating equation model, incident retinal vein occlusion was related to baseline age (odds ratio [OR] per 10 years, 1.70; 95% confidence interval [CI], 1.36-2.12), history of barbiturate use (OR, 5.30; 95% CI, 2.28-12.31), focal retinal arteriolar narrowing (OR, 2.45; 95% CI, 1.29-4.66), glaucoma (OR, 3.17; 95% CI, 1.50-6.69), serum ionized calcium level (OR per 0.4 mg/dL, 0.43; 95% CI, 0.23-0.79), serum phosphorus level (OR per 0.3 mg/dL, 1.15; 95% CI, 1.01-1.30), and serum creatinine level (OR for > or = 1.4 vs < 1.4 mg/dL, 1.61; 95% CI, 1.00-2.59). Migraine headache history was associated with branch retinal vein occlusion (OR, 1.99; 95% CI, 1.08-3.67). Diabetes history was associated with central retinal vein occlusion (OR, 6.35; 95% CI, 1.90-21.27). CONCLUSIONS Incident retinal vein occlusion is not infrequent in the population, especially after age 65 years. The relationships of barbiturate use, serum creatinine level, serum ionized calcium level, and serum phosphorus level with incident retinal vein occlusion require further assessment in other large population-based studies.

Variation associated with measurement of retinal vessel diameters at different points in the pulse cycle

Background/aims: To assess the variability in retinal vessel measurements at different points in the pulse cycle. Methods: A healthy white male aged 19 years had 30 digitised images taken at three distinct points in the pulse cycle over a one hour period. A pulse synchronised ear clip trigger device was used to capture images at the desired point in the pulse cycle. Two trained graders measured the retinal vessel diameter of one large arteriole, one large venule, one small arteriole, and one small venule 10 times in each of these 30 images. Results: Within an image, variability was similar between graders, pulse point, and vessel type. Across images taken at the same point in the pulse period, the change from the minimum to maximum measurement was between 6% and 17% for arterioles and between 2% and 11% for venules. In addition, measurements of small vessels had greater changes than large vessels and no point in the pulse period was more variable than another. Ignoring pulse cycle increased variability across images in the large venule, but not in the other vessel types. Mixed effect models were fit for each of the vessel types to determine the greatest source of variability. Controlling for pulse point and grader, the largest source of variability for all four vessels measured was across images, accounting for more than 50% of the total variability. Conclusion: Measurements of large retinal venules is generally less variable than measurements of other retinal vessels. After controlling for pulse point and grader, the largest source of variation is across images. Understanding the components of variability in measuring retinal vessels is important as these techniques are applied in epidemiological studies.

The epidemiology of progression of pure geographic atrophy: the Beaver Dam Eye Study.

PURPOSE To examine the change in size and location of pure geographic atrophy (GA). DESIGN Population-based cohort study. METHODS Ninety-five persons with GA either at baseline or at the one of the three five-year follow-up examinations, or both, were identified. Using computer-assisted software, the lesion area and greatest linear dimension (GLD) were calculated. Thirty-two persons (53 multiple eye-visit pairs) were seen at multiple visits five years apart with GA in the same eye to evaluate changes in total area and GLD. RESULTS At the first occasion when pure GA was identified (n = 95), 45% had a single GA lesion, 18% had multifocal GA lesions, and 37% had a merged GA lesion. Of 53 eyes with multiple visits, the overall increase in atrophy was 6.4 mm(2) over a five-year period. The atrophy progressed to involve the foveal center in 47% of 19 eyes, and there was a mean decrease of 17 letters read correctly. Eyes with multifocal GA were most likely to have the area of atrophy increase (mean, 12 mm(2)), to have atrophy progress to the foveal center (83%), and to have a decrease in vision (mean, 22 letters), whereas eyes with a single GA lesion were least likely to have the area of atrophy increase (mean, 2 mm(2)), to have the lesion progress to the foveal center (22%), and to have a decrease in vision (mean, 10 letters). CONCLUSIONS These are the first population-based data describing the five-year change in eyes with pure GA. Information on progression of GA will be useful for clinical trials of new interventions for GA.

Prevalence and risk factors for epiretinal membranes in a multi-ethnic United States population

PURPOSE To describe the prevalence of and risk factors for epiretinal membrane (ERM) in a multi-ethnic population and to evaluate possible racial or ethnic differences. DESIGN Cross-sectional study. PARTICIPANTS Participants of the Multi-Ethnic Study of Atherosclerosis (MESA), examined at the second visit of the MESA when retinal photography was performed. METHODS Data on 5960 participants aged 45 to 84 years from MESA, including white, black, Hispanic, and Chinese persons from 6 United States communities, were analyzed. Epiretinal membrane was assessed from digital nonstereoscopic fundus photographs and was defined as cellophane macular reflex (CMR) without retinal folds or preretinal macular fibrosis (PMF) with retinal folds. Risk factors were assessed from standardized interviews, clinical examinations, and laboratory investigations. MAIN OUTCOME MEASURES Epiretinal membrane prevalence by ethnic or racial group and risk factors associated with ERM. RESULTS The prevalence of any ERM was 28.9%, of which 25.1% were CMR cases and 3.8% were PMF cases. The prevalence of ERM was significantly higher in Chinese persons (39.0%), compared with Hispanic (29.3%), white (27.5%), or black (26.2%; P<0.001) persons. In multivariate models, increasing age (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.06-1.34, per year increase in age), diabetes (OR, 1.92; 95% CI, 1.39-2.65), and hypercholesterolemia (OR, 1.33; 95% CI, 1.04-1.69) were significantly associated with CMR. CONCLUSIONS This study showed that ERM was significantly more common in Chinese persons compared with whites, blacks, and Hispanics. Risk factors for ERM were increasing age, presence of diabetes, and hypercholesterolemia.

Quantitation of Optic Disc Cupping

In population-based studies and in clinical practice a reliable, objective measure of optic disc cupping is needed. This measure is of special importance when following patients with diagnosed or suspected glaucoma. We have developed a new system using stereoscopic fundus photographs for quantitating optic disc cupping from these photographs. Measurements of the cup are based on cup contour. For this system, measurements of longest and shortest cup and longest and shortest disc diameters by two observers were highly correlated, with correlation coefficients of 0.88, 0.88, 0.77, and 0.82, respectively. Mean cup to disc ratios for long and short disc diameters were within 0.04 (n = 330) between the two observers. The measurements show a high degree of inter- and intra-observer reliability, and are inexpensive in time and materials to perform. This method is well suited to population-based studies.

Socioeconomic and lifestyle factors and the 10-year incidence of age-related cataracts.

PURPOSE To investigate the association of socioeconomic and lifestyle factors with incidence of age-related cataracts. DESIGN Population-based longitudinal epidemiologic study. METHODS Persons aged 43 to 86 years (n = 4,926) living in Beaver Dam, Wisconsin, were examined in 1988 to 1990, 1993 to 1995, and 1998 to 2000. Medical histories were obtained, and photographs of the lenses were taken at each visit. Photographs were graded according to standard protocols. RESULTS Socioeconomic and lifestyle factors considered were income, education, occupation, smoking, alcohol, caffeine, and multivitamin use. After adjustment for age and sex, income (or education) was inversely and smoking was directly related to the 10-year cumulative incidence of nuclear cataract. None of the factors were significantly associated with incident cortical or posterior subcapsular cataract. We found no evidence in these analyses to suggest that history of multivitamin use altered the relationships of smoking to the incidence of cataracts. In models adjusting for all other significant risk factors, the individual significance values for each individual factor differed little from the models adjusting only for age and sex. CONCLUSIONS Incident nuclear cataract was associated with income and smoking 10 years earlier. There were no significant lifestyle exposures associated with incident cortical and posterior subcapsular cataract.