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Five-year incidence, progression, and risk factors for age-related macular degeneration: the age, gene/environment susceptibility study.

ABSTRACT: OBJECTIVE:To investigate the incidence and progression of age-related macular degeneration (AMD) and associated risk factors. DESIGN:Population-based, prospective, cohort study. PARTICIPANTS:We included 2868 participants from the Age Gene/Environment Susceptibility-Reykjavik Study with retinal data at baseline and 5-year follow-up. METHODS:Digital macular photographs were graded for presence of AMD. Participants completed a questionnaire and extensive clinical battery. Biomarkers were assessed. Risk factors for AMD were analyzed using multivariate regression analysis with odds ratios (ORs) and 95% CIs. MAIN OUTCOME MEASURES:We assessed AMD, defined as early or late. RESULTS:Among 2196 participants free of AMD at baseline, 14.9% developed incident AMD. In multivariate models, incident AMD was significantly associated with age (OR per year, 1.14; 95% CI, 1.11-1.17), current smoking (OR, 2.07; 95% CI, 1.38-3.11), former smoking (OR, 1.36; 95% CI, 1.04-1.79), plasma high-density lipoprotein (HDL) cholesterol level (OR, 1.62 per mmol/L; 95% CI, 1.19-2.22), and body mass index (BMI; OR, 1.04 per kg/m(2); 95% CI, 1.01-1.07). Among 563 participants with early AMD at baseline, 22.7% progressed to late AMD (11.0% pure geographic atrophy [GA] and 11.7% exudative AMD). On multivariate analyses, age was significantly associated with progression to GA (OR 1.14; 95% CI, 1.07-1.21) and exudative AMD (OR, 1.08; 95% CI, 1.01-1.14). Adjusting for age, female sex was associated with exudative AMD (OR, 2.10; 95% CI, 1.10-3.98) and plasma HDL cholesterol with GA (OR, 2.03 per mmol/L; 95% CI, 1.02-4.05). CONCLUSIONS:By age 85, 57.4% of participants had signs of AMD. Age, smoking, plasma HDL cholesterol, BMI, and female sex are associated with AMD. Elevated HDL cholesterol is associated with GA development.

SUBMITTER: Jonasson F

PROVIDER: S-EPMC4145014 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Five-year incidence, progression, and risk factors for age-related macular degeneration: the age, gene/environment susceptibility study.

Jonasson Fridbert F Fisher Diana E DE Eiriksdottir Gudny G Sigurdsson Sigurdur S Klein Ronald R Launer Lenore J LJ Harris Tamara T Gudnason Vilmundur V Cotch Mary Frances MF

Ophthalmology 20140424 9

<h4>Objective</h4>To investigate the incidence and progression of age-related macular degeneration (AMD) and associated risk factors.<h4>Design</h4>Population-based, prospective, cohort study.<h4>Participants</h4>We included 2868 participants from the Age Gene/Environment Susceptibility-Reykjavik Study with retinal data at baseline and 5-year follow-up.<h4>Methods</h4>Digital macular photographs were graded for presence of AMD. Participants completed a questionnaire and extensive clinical batter ...[more]

PMID: 24768241

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Project description:PURPOSE:Age-related macular degeneration (AMD) is a degenerative disease of the macula, often leading to progressive vision loss. The rate of disease progression can vary among individuals and has been associated with multiple risk factors. In this review, we provide an overview of the current literature investigating phenotypic, demographic, environmental, genetic, and molecular risk factors, and propose the most consistently identified risk factors for disease progression in AMD based on these studies. Finally, we describe the potential use of these risk factors for personalised healthcare. RECENT FINDINGS:While phenotypic risk factors such as drusen and pigment abnormalities become more important to predict disease progression during the course of the disease, demographic, environmental, genetic and molecular risk factors are more valuable at earlier disease stages. Demographic and environmental risk factors such as age and smoking are consistently reported to be related to disease progression, while other factors such as sex, body mass index (BMI) and education are less often associated. Of all known AMD variants, variants that are most consistently reported with disease progression are rs10922109 and rs570618 in CFH, rs116503776 in C2/CFB/SKIV2L, rs3750846 in ARMS2/HTRA1 and rs2230199 in C3. However, it seems likely that other AMD variants also contribute to disease progression but to a lesser extent. Rare variants have probably a large effect on disease progression in highly affected families. Furthermore, current prediction models do not include molecular risk factors, while these factors can be measured accurately in the blood. Possible promising molecular risk factors are High-Density Lipoprotein Cholesterol (HDL-C), Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), zeaxanthin and lutein. SUMMARY:Phenotypic, demographic, environmental, genetic and molecular risk factors can be combined in prediction models to predict disease progression, but the selection of the proper risk factors for personalised risk prediction will differ among individuals and is dependent on their current disease stage. Future prediction models should include a wider set of genetic variants to determine the genetic risk more accurately, and rare variants should be taken into account in highly affected families. In addition, adding molecular factors in prediction models may lead to preventive strategies and personalised advice.

Project description:ImportanceThe incidence of age-related macular degeneration (AMD) is unknown in Africa.ObjectiveTo estimate the 6-year cumulative incidence and progression of AMD in older adults (≥50 years old) in Nakuru, Kenya.Design, setting, and participantsThis study assessed a population-based cohort with 6-year follow-up of 4414 participants who had a complete assessment. Random cluster sampling with probability proportionate to size procedures was used to select a representative, cross-sectional sample of adults 50 years and older from January 26, 2007, through November 11, 2008. A 6-year follow-up was undertaken from January 7, 2013, through March 12, 2014. On both occasions, a comprehensive ophthalmic examination was performed that included logMAR visual acuity, digital retinal photography, and grading of images at Moorfields Eye Hospital Reading Centre. Data were collected on general health and risk factors.Main outcomes and measuresIncident AMD in participants with no AMD at baseline and progression from early to late AMD.ResultsA total of 1453 of the 2900 individuals (50.1%) at risk for AMD were followed up after 6 years (mean [SD] age, 60.7 [8.2] years; 635 female [49.5%]; 799 Kikuyu [62.3%], 324 Kalenjin [25.3%], and 159 other [12.4%]); 1282 had data on AMD status at follow-up. Of these, 202 developed early AMD, and no participants developed late AMD. The 6-year weighted (for loss to follow-up) cumulative incidence of early AMD was 164.2 per 1000 persons (95% CI, 136.7-195.9 per 1000 persons). Two individuals with baseline early AMD from the 142 at risk had developed late AMD at follow-up, with a 6-year cumulative incidence of progression from early to late AMD of 24.5 per 1000 persons (95% CI, 5.0-111.7 per 1000 persons). Cumulative incidence of AMD increased with age (≥80 years old vs 50-59 years old: 1.8; 95% CI, 0.9-3.5) and was higher in women (female vs male: 1.6; 95% CI, 1.2-2.1) and persons with diabetes (diabetes vs no diabetes: 1.7; 95% CI, 1.0-2.8).Conclusions and relevanceIn Kenya, more than 100 000 estimated new cases of AMD, mainly early AMD, will develop every year in individuals 50 years or older, although a 50% loss to follow-up and wide CIs for progression to late AMD limit definitive conclusions from these findings.

Project description:Importance:Whether a reported decline in the risk of developing age-related macular degeneration (AMD) continued for people born during the Baby Boom years (1946-1964) or later is unknown. These data are important to plan for ocular health care needs in the 21st century. Objectives:To determine whether the 5-year risk for AMD declined by generation and to identify factors that contributed to improvement in risk. Design, Setting, and Participants:Data came from the longitudinal cohort Beaver Dam Eye Study (March 1, 1988, through September 15, 1990, and March 1, 1993, through June 15, 1995) and the Beaver Dam Offspring Study (June 8, 2005, through August 4, 2008, and July 12, 2010, through March 21, 2013). These population-based studies examined residents of Beaver Dam, Wisconsin, aged 43 to 84 years in 1987 through 1988 and their adult offspring aged 21 to 84 years in 2005 through 2008. A total of 4819 participants were at risk for developing AMD based on fundus images obtained at baseline visits. Data were analyzed from February 18, 2016, through June 22, 2017, with additional analyses ending September 22, 2017. Main Outcomes and Measures:Fundus images were graded for AMD using the Wisconsin Age-related Maculopathy Grading System. The incidence of AMD was defined as the presence at the 5-year follow-up examination of pure geographic atrophy or exudative macular degeneration, any type of drusen with pigmentary abnormalities, or soft indistinct drusen without pigmentary abnormalities. Results:Among the 4819 participants, the mean (SD) baseline age of the cohort was 54 (11) years; 2117 were men (43.9%) and 2702 were women (56.1%). The 5-year age- and sex-adjusted incidence of AMD was 8.8% in the Greatest Generation (born during 1901-1924), 3.0% in the Silent Generation (born during 1925-1945), 1.0% in the Baby Boom Generation (born during 1946-1964), and 0.3% in Generation X (born during 1965-1984). Adjusting for age and sex, each generation was more than 60% less likely to develop AMD than the previous generation (relative risk, 0.34; 95% CI, 0.24-0.46). The generational association (relative risk, 0.40; 95% CI, 0.28 to 0.57) remained significant after adjusting for age, sex, smoking, educational attainment, exercise, levels of non–high-density lipoprotein cholesterol and high-sensitivity C-reactive protein, and use of nonsteroidal anti-inflammatory drugs, statins, and multivitamins. Conclusions and Relevance:The 5-year risk for AMD declined by birth cohorts throughout the 20th century. Factors that explain this decline in risk are not known. However, this pattern is consistent with reported declines in risks for cardiovascular disease and dementia, suggesting that aging Baby Boomers may experience better retinal health at older ages than did previous generations.

Project description:While the prevalence of age-related macular degeneration (AMD) differs according to continents and races/ethnicities, its incidence in the European continent has been scarcely documented.To describe the incidence and associated risk factors of AMD in elderly French individuals.This population-based cohort study of 963 residents of Bordeaux, France, who were 73 years or older at baseline and participated in the Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (ALIENOR) Study between October 2, 2006, and December 21, 2012. Of 829 participants at risk for incident AMD, 659 (79.5%) were observed for a mean (SD) duration of 3.8 (1.1) years. Data were analyzed from August 2016 to March 2017.Age-related macular degeneration was graded from retinal photographs and spectral-domain optical coherence tomography into 5 exclusive stages: no AMD, early AMD1, early AMD2, late atrophic AMD, and late neovascular AMD.Of the 659 eligible participants, 413 (62.7%) were women, and the mean (SD; range) age was 79.7 (4.4; 73-94) years. A total of 120 incident cases of early AMD and 45 incident cases of advanced AMD were recorded. Incidence rates of early and advanced AMD were 79.9 (95% CI, 66.8-95.5) per 1000 person-years and 18.6 (95% CI, 13.9-24.9) per 1000 person-years, respectively, corresponding to 5-year risks of 32.9% and 8.9%. Incidence of advanced AMD per 1000 eye-years was 1.5 in eyes without any AMD at baseline, 42.4 in those with early AMD1, and 85.1 in those with early AMD2. In multivariate analysis without correction for multiple testing, progression from early to advanced AMD was associated with AMD grade in the fellow eye (hazard ratio [HR] according to grade, 13.0 [95% CI, 2.8-61.2] to 22.5 [95% CI, 2.6-195.9]), having smoked at least 20 pack-years (calculated as number of smoking years × mean number of cigarettes per day / 20; HR, 3.0; 95% CI, 1.4-6.5), and complement factor H (CFH) Y402H genotype (CC genotype: HR, 2.3; 95% CI, 1.0-5.3; TC genotype: HR, 1.5; 95% CI, 0.6-3.7). Incidence of early AMD was associated with early AMD in the fellow eye (early AMD1: HR, 2.6; 95% CI, 1.6-4.2; early AMD2: HR, 5.6; 95% CI, 3.3-9.4) and high plasma high-density lipoprotein cholesterol levels (HR, 1.2; 95% CI, 1.0-1.4).In this cohort, AMD incidence rates were similar to those observed in other European populations. This study suggests a high risk for incident early AMD in individuals with high plasma high-density lipoprotein cholesterol levels while confirming the high risk for progression from early to advanced AMD in heavy smokers and carriers of CFH Y402H at-risk genotypes.

Project description:PurposeTo describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD).DesignCohort study.ParticipantsPatients enrolled in the Comparison of AMD Treatments Trials.MethodsPatients were assigned randomly to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After 2 years, patients were released from the clinical trial protocol. At 5 years, patients were recalled for examination.Main outcome measuresVisual acuity (VA) and morphologic retinal features.ResultsVisual acuity was obtained for 647 of 914 (71%) living patients with average follow-up of 5.5 years. The mean number of examinations for AMD care after the clinical trial ended was 25.3, and the mean number of treatments was 15.4. Most patients (60%) were treated 1 time or more with a drug other than their assigned drug. At the 5-year visit, 50% of eyes had VA of 20/40 or better and 20% had VA of 20/200 or worse. Mean change in VA was -3 letters from baseline and -11 letters from 2 years. Among 467 eyes with fluorescein angiography, mean total lesion area was 12.9 mm(2), a mean of 4.8 mm(2) larger than at 2 years. Geographic atrophy was present in 213 of 515 (41%) gradable eyes and was subfoveal in 85 eyes (17%). Among 555 eyes with spectral-domain optical coherence tomography, 83% had fluid (61% intraretinal, 38% subretinal, and 36% sub-retinal pigment epithelium). Mean foveal total thickness was 278 μm, a decrease of 182 μm from baseline and 20 μm from 2 years. The retina was abnormally thin (<120 μm) in 36% of eyes. Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more VA than the bevacizumab group (-4 letters; P = 0.008). Otherwise, there were no statistically significant differences in VA or morphologic outcomes between drug or regimen groups.ConclusionsVision gains during the first 2 years were not maintained at 5 years. However, 50% of eyes had VA of 20/40 or better, confirming anti-vascular endothelial growth factor therapy as a major long-term therapeutic advance for neovascular AMD.

Project description:PurposeTo evaluate associations of morphologic features with 5-year visual acuity (VA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).DesignCohort study within a randomized clinical trial.ParticipantsParticipants in CATT.MethodsEyes with age-related macular degeneration-associated choroidal neovascularization (CNV) and VA between 20/25 and 20/320 were eligible. Treatment was assigned randomly to ranibizumab or bevacizumab and to 3 dosing regimens for 2 years and was at the ophthalmologists' discretion thereafter.Main outcome measuresVisual acuity, thickness and morphologic features on OCT, and lesion size and foveal composition on fundus photography (FP) and fluorescein angiography (FA).ResultsVisual acuity and image gradings were available for 523 of 914 participants (57%) alive at 5 years. At 5 years, 60% of eyes had intraretinal fluid (IRF), 38% had subretinal fluid (SRF), 36% had subretinal pigment epithelium (RPE) fluid, and 66% had subretinal hyper-reflective material (SHRM). Mean (standard deviation) foveal center thickness was 148 μm (99) for retina, 5 μm (21) for SRF, 125 μm (107) for subretinal tissue complex, 11 μm (33) for SHRM, and 103 μm (95) for RPE + RPE elevation. The SHRM, thinner retina, greater CNV lesion area, and foveal center pathology (all P < 0.001) and IRF (P < 0.05) were independently associated with worse VA. Adjusted mean VA letters were 62 for no pathology in the foveal center; 61 for CNV, fluid, or hemorrhage; 65 for non-geographic atrophy (GA); 64 for nonfibrotic scar; 53 for GA; and 56 for fibrotic scar. Incidence or worsening of 8 pathologic features (foveal GA, foveal scar, foveal CNV, SHRM, foveal IRF, retinal thinning, CNV lesion area, and GA area) between years 2 and 5 was independently associated with greater loss of VA from years 2 to 5 and VA loss from baseline to year 5.ConclusionsAssociations between VA and morphologic features previously identified through year 1 were maintained or strengthened at year 5. New foveal scar, CNV, intraretinal fluid, SHRM and retinal thinning, development or worsening of foveal GA, and increased lesion size are important contributors to the VA decline from years 2 to 5. A significant need to develop therapies to address these adverse pathologic features remains.

Project description:OBJECTIVE:To investigate the association between age-related macular degeneration (AMD) and mortality in older persons. DESIGN:Population-based prospective cohort study. PARTICIPANTS:Participants 67 to 96 years of age (43.1% male) enrolled between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study. METHODS:Retinal photographs of the macula were acquired digitally and evaluated for the presence of AMD lesions using the Wisconsin Age-Related Maculopathy grading scheme. Mortality was assessed prospectively through 2013 with cause of death available through 2009. The association between AMD and death, resulting from any cause and specifically cardiovascular disease (CVD), was examined using Cox proportional hazards regression with age as the time scale, adjusted for significant risk factors and comorbid conditions. To address a violation in the proportional hazards assumption, analyses were stratified into 2 groups based on the mean age at death (83 years). MAIN OUTCOME MEASURES:Mortality resulting from all causes and CVD. RESULTS:Among 4910 participants, after a median follow-up of 8.6 years, 1742 died (35.5%), of whom 614 (35.2%) had signs of AMD at baseline. Cardiovascular disease was the cause of death for 357 people who died before the end of 2009, of whom 144 (40%) had AMD (101 with early disease and 43 with late disease). After considering covariates, including comorbid conditions, having early AMD at any age or having late AMD in individuals younger than 83 years (n = 4179) were not associated with all-cause or CVD mortality. In individuals 83 years of age and older (n = 731), late AMD was associated significantly with increased risk of all-cause mortality (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.20-2.57) and CVD-related mortality (HR, 2.37; 95% CI, 1.41-3.98). In addition to having AMD, older individuals who died were more likely to be male and to have low body mass index, impaired cognition, and microalbuminuria. CONCLUSIONS:Competing risk factors and concomitant conditions are important in determining mortality risk resulting from AMD. Individuals with early AMD are not more likely to die than peers of comparable age. Late AMD becomes a predictor of mortality by the mid-octogenarian years.

Dataset Information

Five-year incidence, progression, and risk factors for age-related macular degeneration: the age, gene/environment susceptibility study.

Publications

Five-year incidence, progression, and risk factors for age-related macular degeneration: the age, gene/environment susceptibility study.

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