Progression Of Age-related Maculopathy Research Articles

Expression and location of ARMS2 protein in normal eye tissue

Background Researches determined that the alteration of A69S locus of age-related maculopathy susceptibility 2 ( ARMS2 ) gene is closely associated with the pathogenesis and progression of age-related maculopathy ( AM D ).However,the location of ARMS2 protein in normal eye tissue is still in controversy,therefore,its function is below understanding up to now.Objective The goal of this laboratory work was to investigate the distribution,expression and location of ARMS2 protein in normal adult retina and choroid as well as in retinal pigment epithelial (RPE) cells and lay a basis for exploring further its function in the protein level.Methods Ten donor eyeballs of normal adult male with the age from 28-42 years were collected in eye bank of Qingdao Eye Hospital.The frozen sections of the retina and choroid were prepared for the detection and location of ARMS2 in 3 eyes by immunofluorescence under the confocal laser microscope.The retina was isolated for the primary culture of RPE cells using explant culture method.The cells were then identified by CK32 antibody by immunofluorescence.The distribution and expression of the ARMS2 protein in retina,ehoroid and RPE cells were determined by immunofluorescence technique.Results ARMS2 protein was strongly expressed in retinal vessel,RPE cell layer,Bruch membrane and choroidal vessel,but weak expression was in retinal ganglion cell layer,inner nuclear layer,outer plexiform layer,outer nuclear layer and inner plexiform layer in the normal eyes.The primarily cultured cells appeared the polygon shape with the abundant pigment in cytoplasm.The immunofluorescence of the cells showed the positive response for CK32,exhibiting the green fluorescence granules in the cytoplasm.The positive expression of ARMS2 protein also was seen in the cytoplasm of RPE cells,appearing the red fluorescence.Conclusions ARMS2 protein mainly distribute and locate retinal and choroidal vessels,RPE cells and Bruch membrane in normal eye. Key words: Age-related maculopathy susceptibility 2; Retinal pigment epithelium; Choroid; Bruch membrane

Susceptibility Genes and Progression in Age-Related Maculopathy: A Study of Single Eyes

The specific role of single-nucleotide polymorphisms (SNPs) in the progression of age-related maculopathy (AMD) is not clearly understood. The present study was conducted to investigated whether variants in three susceptibility genes are differentially associated with progression to early and late AMD. The Münster Ageing and Retina Study (MARS) cohort includes 722 patients with different stages of AMD. Participants were reexamined after a median of 2.6 years. The association of SNPs in the CFH, ARMS2, and C3 genes with AMD progression was evaluated in 1435 single eyes by using multivariate logistic regression models with generalized estimating equations. CFH-rs1061170 was significantly related to the development of early (OR = 1.94, 95% confidence interval [CI], 1.3-3.0 for heterozygous, and OR = 2.9 [95% CI, 1.7-5.1] for homozygous allele carriers) but not to late AMD. In contrast, ARMS2-rs10490924 was associated only with progression to advanced disease (OR = 1.2 [0.7-2.1] and OR = 2.1 [1.1-3.9], respectively). The variant C3-rs2230199 showed no relation with AMD progression. The findings indicate that AMD progression is differentially affected by genotypic variants. Probably, aging processes of the human retina predispose to AMD onset in the presence of genetic variation in the complement system, which alters immunoregulatory and inflammatory responses. The specific functional role of ARMS2-rs10490924 remains as yet unknown, but it appears to mainly affect the progression to late AMD stages.

Ethnic Differences in Macular Pigment Density and Distribution

Many epidemiologic studies suggest a number of risk factors that may be associated with progression of age-related maculopathy (ARM). In this study, the authors investigate ethnic differences in macular pigment density (MPD) and macular pigment (MP) distribution. Inclusion criteria were healthy subjects, aged 35 to 49 years, visual acuity >or=20/20, race ethnicity white non-Hispanic (WNH) or African. All subjects underwent the following examinations: best-corrected ETDRS visual acuity (VA), measurements of MPD, and spatial distribution of MP with a modified confocal scanning laser ophthalmoscope according to a standard protocol. MPD maps were calculated from autofluorescence images recorded at 488 nm and 514 nm. Central macular pigment density (MPDc) was quantified from MPD maps within 0.5 degrees around the center of the fovea. In total, 118 healthy subjects (61 women, 57 men) aged 35 to 49 years (mean, 42.5 +/- 3.6 years) were recruited for the study. Sixty-seven healthy subjects were WNH and 51 were African. Visual acuity ranged from 20/20 to 20/16 in the study eye. Significant differences were found among MPDc between the group of WNH (MPDc, 0.36 +/- 0.13 density units [DU]; P < 0.0001) and African subjects (MPDc, 0.59 +/- 0.14 DU). A parafoveal ring was significantly more frequent in African subjects than in WNH subjects (86% [African] vs. 68% [WNH]; P < 0.0001). This study demonstrates that ethnicity plays a role in MPD values and in MP distribution. The association of different distribution patterns and their relevance as possible prognostic factors for diseases leading to oxidative retinal damage requires further studies.

Ten-Year Incidence and Progression of Age-Related Maculopathy: The Blue Mountains Eye Study

To assess the 10-year incidence of age-related maculopathy (ARM) in an older Australian cohort. Population-based cohort study. Three thousand six hundred fifty-four Blue Mountains Eye Study participants > or =49 years old were examined during 1992 through 1994; 2335 (75% of survivors) were reexamined after 5 years (1997-1999) and 1952 (76% of survivors) after 10 years (2002-2004). The same graders performed retinal photographic grading in all examinations, using the Wisconsin Age-Related Maculopathy Grading System. Photographs of participants with ARM lesions at any of the examinations were subsequently regraded using a side-by-side comparison method. The diagnosis of incident late ARM was given if neovascular ARM or geographic atrophy was detected at either follow-up examination in persons free of these lesions at baseline. Incident early ARM was diagnosed if early ARM (soft indistinct or reticular drusen or combined soft distinct drusen and retinal pigment abnormality) was present in persons free of early and late ARM at baseline. Age-related maculopathy incidence was calculated using Kaplan-Meier methods to incorporate information from both 5- and 10-year examinations. Discrete logistic models were used to assess the risk of incident late ARM according to various baseline factors, including early ARM lesion characteristics. After excluding 72 late ARM cases present at baseline, 2395 of 3582 subjects at risk of late ARM (67%) were reexamined at either follow-up time point or both follow-up time points. Over the 10-year period, 72 of 2395 subjects (3.7%) developed late ARM and 266 of 2255 subjects (14.1%) developed early ARM. After age standardization to the Beaver Dam Eye Study population, our 10-year incidences of late and early ARM were 2.8% and 10.8%, respectively. Baseline age and early ARM lesion characteristics and severity were strong predictors of late ARM incidence. Long-term follow-up of this older population confirms that the risk of ARM progression is related strongly to the severity of early-stage lesions. The study provides evidence-based criteria for identifying persons at high risk of developing late ARM.

Macular pigment density in age-related maculopathy

Macular pigment (MP) is believed to have a protective role in the development and progression of age-related maculopathy (ARM). We present results of measurements of macular pigment density (MPD) in patients with ARM at different stages with a modified confocal scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Heidelberg, Germany). ARM patients were categorized into four groups. Staging depended upon the size of drusen, geographic atrophy, and loss of visual acuity due to ARMD in the fellow eye; 1: drusen size <125 microm, 2: drusen size >125 microm, 3: drusen size <125 microm + ARMD in fellow eye, and 4: drusen size >125 microm + ARMD in fellow eye. We took autofluorescence images at 488 nm and 514 nm with a modified HRA. MP density was evaluated within 2 degrees around the center of the fovea. In this study, we included 146 patients with ARM: 26 in group 1, 19 in group 2, 80 in group 3, and 21 in group 4. The mean MPD of the different stages of ARM was: in group 1, 0.233 +/- 0.091 DU; group 2, 0.218 +/- 0.102 density units (DU); group 3, 0.252 +/- 0.085 DU; and group 4, 0.208 +/- 0.100 DU. Statistical analysis (Kruskal-Wallis test) showed no differences between groups. Recent studies in ARM did not result in significant differences of MPD between the various stages of ARM. Further longitudinal studies are requested to compare the incidence of ARMD in eyes with high and low MPD in order to provide definite evidence of the influence of MPD on the progression of ARMD.

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

To examine the association of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) with the 5-year incidence of age-related maculopathy (ARM). 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. 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. Incidence and progression of ARM was measured over the 5-year interval. 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). 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.

Macular pigment density in healthy subjects quantified with a modified confocal scanning laser ophthalmoscope.

In the industrialized world age-related macular degeneration (ARMD) is the leading cause for legal blindness beyond the age of 65 years. Recent studies indicate that the density of the macular pigment (MP) may play a central role in the development and progression of age-related maculopathy (ARM). We present results of measurements of macular pigment density (MPD) with a modified confocal scanning laser ophthalmoscope and compare macular pigment density values obtained from reflectance and autofluorescence images in healthy subjects. A modified confocal scanning laser ophthalmoscope (Heidelberg Engineering, Heidelberg) was optimised for fundus reflectance and autofluorescence images at 488 nm and 514 nm. For autofluorescence imaging a band pass barrier filter with a short wavelength cut off at 530 nm was used. MPD maps were obtained, and MPD was evaluated within two degrees around the foveal center. In this study we included 109 healthy subjects aged from 18-75 years. Average MPD ranged between 0.16 density units (D.U.) and 0.22 D.U. depending on the techniques used for the measurement. Using the reflectance method the mean MPD was 0.16+/-0.06 D.U., whereas a MPD of 0.22+/-0.07 D.U. resulted from autofluorescence images with the 530-nm barrier filter. This study demonstrates the good feasibility of MPD measurements with a modified confocal SLO. In agreement with previous studies we found higher macular pigment density values calculated from autofluorescence images than from reflectance images. We could not find any differences in MPD related to age and gender. Prospective longitudinal studies to verify the influence of MPD on the development and progression of ARM are needed.

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.

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

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. Population-based cohort study. 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. 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. Incidence and progression of age-related maculopathy. 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). 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.

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 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 μm-249 μm, 26.3% vs. 3.3%; ≥250 μm, 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.

Vitamin E supplementation and macular degeneration: randomised controlled trial

Objective: To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy (AMD).Design: Prospective randomised placebo controlled clinical trial.Setting: An urban study centre in...

The relationship of ocular factors to the incidence and progression of age-related maculopathy.

To examine the association between ocular factors and the incidence and progression of age-related maculopathy. A population of 3684 adults (43-86 years of age at baseline) living in Beaver Dam, Wis, studied at baseline and 5 years later. Standardized protocols for refraction and determination of iris color, administration of a questionnaire, and slitlamp and retroillumination photographs of the lenses to determine cataract type and stereoscopic color fundus photographs to determine presence and severity of age-related maculopathy. Standard univariate and multivariate analyses were performed. Incidence and progression of age-related maculopathy. After controlling for age, eyes that had undergone cataract surgery before baseline were more likely to have progression of age-related maculopathy (odds ratio, 2.71; 95% confidence interval [CI], 1.69-4.35) and to develop signs of late age-related maculopathy (odds ratio, 2.80; 95% CI, 1.03-7.63) than were eyes that were phakic at baseline. These relationships remained after controlling for other risk factors in multivariate analyses. There was no relationship of nuclear cataract, cortical cataract, or iris color to the incidence and progression of age-related maculopathy. These findings indicate a relationship between cataract surgery and increased risk of progression of age-related maculopathy.

The Relation of Cardiovascular Disease and Its Risk Factors to the 5-year Incidence of Age-related Maculopathy: The Beaver Dam Eye Study

Objective: The purpose of the study is to examine the association between cardiovascular disease and its risk factors and the incidence of age-related maculopathy.Participants: A population of 3583 adults (range, 43–86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied at baseline and 5 years later.Methods: Standardized protocols for physical examination, blood collection, administration of a questionnaire, and stereoscopic color fundus photography to determine agerelated maculopathy were used. Standard univariate and multivariate analyses were performed.Main Outcome Measures: Incidence and progression of age-related maculopathy were measured.Results: After controlling for age and gender, the authors found both higher systolic blood pressure (odds ratio [OR] per 10 mmHg, 1.16; 95% confidence interval [CI] 1.05, 1.27) and uncontrolled treated hypertension (OR 1.98, 95% CI 1.00, 3.94) were related to the incidence of retinal pigment epithelial depigmentation. After controlling for age and gender, the authors found that both blood pressure and uncontrolled treated hypertension were not significantly associated with an increased risk of having exudative macular degeneration develop (for systolic blood pressure, OR 1.18, 95% CI 0.95,1.45; for uncontrolled treated hypertension, OR 2.10, 95% CI 0.54, 8.11). After controlling for age and gender, the authors found higher pulse pressure was significantly associated with increased incidence of retinal pigment epithelial depigmentation (OR per 10 mmHg 1.27, 95% CI 1.14, 1.42) and exudative macular degeneration (OR per 10 mmHg 1.29, 95% CI 1.02, 1.65). These relations remained significant after controlling for other risk factors in multivariable analyses.Conclusions: These findings indicate modest relations between higher pulse pressure (a presumed indicator of atherosclerotic vascular disease) and uncontrolled hypertension with increased 5-year incidence of retinal pigment epithelial depigmentation. Overall, however, data from this study show neither consistent nor strong relations between cardiovascular disease and most of its risk factors with the incidence of lesions associated with age-related maculopathy.

The Five-year Incidence and Progression of Age-related Maculopathy: The Beaver Dam Eye Study

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. 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. 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. 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. 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.