Incidence Of Late Age-related Macular Degeneration Research Articles

Associations of drusen location with risk factors and incidence of late age-related macular degeneration in the Alienor study.

To test the hypothesis that central drusen location is strongly linked with known Age-related Macular Degeneration (AMD) risk factors and risk of incident late AMD. The Alienor study is a prospective population-based cohort study of residents of Bordeaux, France, followed from 2009 to 2017. On retinal photographs, we defined central drusen as at least one soft drusen (>63 μm) within 500 μm from fovea and pericentral drusen as at least one drusen 500-3000 μm from fovea, in the absence of any central drusen. Late AMD (atrophic and/or neovascular) was diagnosed using multimodal imaging. In total, 481 eyes were included in the analysis: 160 central and 321 pericentral. We investigated associations with systemic (age, sex, smoking, medical prescriptions, plasma concentrations of lipids and nutrients, UV exposure, blood pressure), ocular (retinal thickness, cataract extraction) and genetic risk scores (GRS). In multivariate logistic regression central drusen were associated with smoking (OR, 2.95 for smoking more than 20 pack-years, p = 0.02), HDL-cholesterol (OR, 1.57 for 1 standard deviation (SD) increase, p = 0.0048), pulse pressure (OR, 0.77 for 1 SD increase, p = 0.04), Age-Related Maculopathy Susceptibility 2 (ARMS2) GRS (OR, 1.42; 95% CI, 1.11-1.83) and complement GRS (OR, 1.55; 95% CI, 1.15-2.10). In Cox modelling, the central location of drusen (at baseline or during the follow-up) was associated with a 4.41-fold increased risk (95% CI,1.98-9.81) for an incident late AMD. Central drusen were strongly associated with AMD risk factors and incident late AMD, suggesting that it represents a key marker for AMD progression.

Incidence, progression and risk factors of age-related macular degeneration in 35–95-year-old individuals from three jointly designed German cohort studies

ObjectiveTo estimate age-related macular degeneration (AMD) incidence/progression across a wide age range.Methods and analysisAMD at baseline and follow-up (colour fundus imaging, Three Continent AMD Consortium Severity Scale, 3CACSS, clinical classification,...

Cataract Surgery and the Risk of Developing Late Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 Report Number 27

To evaluate the risk of developing late age-related macular degeneration (AMD) after incident cataract surgery. A prospective cohort study within a randomized controlled clinical trial of oral supplementation for the treatment of AMD, the Age-Related Eye Disease Study 2 (AREDS2). AREDS2 participants aged 50 to 85 years with bilateral large drusen or unilateral late AMD. In eyes free of cataract surgery and late AMD at baseline, 2 groups were compared for incident late AMD: (1) eyes that received cataract surgery after the baseline visit and before any evidence of late AMD and (2) eyes that remained phakic until study completion. Eyes with at least 2 years of follow-up after cataract surgery were included in the analysis. We used Cox regression models, matched-pairs analysis, and logistic regression models that were adjusted for age, sex, smoking, education, study treatment group, and AMD severity. Late AMD was defined as the presence of geographic atrophy or neovascular AMD detected on annual stereoscopic fundus photographs or as documented by medical records, including intravitreous injections of anti-vascular endothelial growth factor medication. A total of 1767 eligible eyes (1195 participants) received cataract surgery; 1981 eyes (1524 participants) developed late AMD during a mean (range) follow-up of 9 (1-12) years. The Cox regression model showed no increased risk of developing late AMD after cataract surgery: hazard ratio, 0.96; 95% confidence interval (CI), 0.81-1.13 (P= 0.60) for right eyes and hazard ratio, 1.05; 95% CI, 0.89-1.25 (P= 0.56) for left eyes. Of the matched pairs, late AMD was identified in 408 eyes that received cataract surgery and in 429 phakic controls: odds ratio (OR) 0.92 (95% CI, 0.77-1.10; P= 0.34). The risk of late AMD after cataract surgery from the logistic regression model was not statistically significant (risk ratio, 0.92; 95% CI, 0.56-1.49; P= 0.73). Cataract surgery did not increase the risk of developing late AMD among AREDS2 participants with up to 10 years of follow-up. This study provides data for counseling AMD patients who might benefit from cataract surgery.

Impact of incident age-related macular degeneration and associated vision loss on vision-related quality of life

BackgroundWe examined the associations between the 6-year incidence of age-related macular degeneration (AMD) and vision-related quality of life (VRQoL), and the contribution of presenting visual acuity (VA), in an Asian...

Geographic distributions of age-related macular degeneration incidence: a systematic review and meta-analysis

PurposeWe performed a systematic review and meta-analysis to summarise the geographic distribution of age-related macular degeneration (AMD) incidence.MethodsDatabases including PubMed, Embase and Web of Science were searched for publications of...

Performance of Classification Systems for Age-Related Macular Degeneration in the Rotterdam Study.

PurposeTo compare frequently used classification systems for age-related macular degeneration (AMD) in their abilty to predict late AMD.MethodsIn total, 9066 participants from the population-based Rotterdam Study were followed up for progression of AMD during a study period up to 30 years. AMD lesions were graded on color fundus photographs after confirmation on other image modalities and grouped at baseline according to six classification systems. Late AMD was defined as geographic atrophy or choroidal neovascularization. Incidence rate (IR) and cumulative incidence (CuI) of late AMD were calculated, and Kaplan-Meier plots and area under the operating characteristics curves (AUCs) were constructed.ResultsA total of 186 persons developed incident late AMD during a mean follow-up time of 8.7 years. The AREDS simplified scale showed the highest IR for late AMD at 104 cases/1000 py for ages <75 years. The Rotterdam classification showed the highest IR at 89 cases/1000 py >75 years. The 3-Continent harmonization classification provided the most stable progression. Drusen area >10% ETDRS grid (hazard ratio 30.05, 95% confidence interval [CI] 19.25–46.91) was most prognostic of progression. The highest AUC of late AMD (0.8372, 95% CI: 0.8070-0.8673) was achieved when all AMD features present at baseline were included.ConclusionsHighest turnover rates from intermediate to late AMD were provided by the AREDS simplified scale and the Rotterdam classification. The 3-Continent harmonization classification showed the most stable progression. All features, especially drusen area, contribute to late AMD prediction.Translational RelevanceFindings will help stakeholders select appropriate classification systems for screening, deep learning algorithms, or trials.

Artificial Intelligence to Stratify Severity of Age-Related Macular Degeneration (AMD) and Predict Risk of Progression to Late AMD.

PurposeTo build and validate artificial intelligence (AI)-based models for AMD screening and for predicting late dry and wet AMD progression within 1 and 2 years.MethodsThe dataset of the Age-related Eye Disease Study (AREDS) was used to train and validate our prediction model. External validation was performed on the Nutritional AMD Treatment-2 (NAT-2) study.First StepAn ensemble of deep learning screening methods was trained and validated on 116,875 color fundus photos from 4139 participants in the AREDS study to classify them as no, early, intermediate, or advanced AMD and further stratified them along the AREDS 12 level severity scale. Second step: the resulting AMD scores were combined with sociodemographic clinical data and other automatically extracted imaging data by a logistic model tree machine learning technique to predict risk for progression to late AMD within 1 or 2 years, with training and validation performed on 923 AREDS participants who progressed within 2 years, 901 who progressed within 1 year, and 2840 who did not progress within 2 years. For those found at risk of progression to late AMD, we further predicted the type (dry or wet) of the progression of late AMD.ResultsFor identification of early/none vs. intermediate/late (i.e., referral level) AMD, we achieved 99.2% accuracy. The prediction model for a 2-year incident late AMD (any) achieved 86.36% accuracy, with 66.88% for late dry and 67.15% for late wet AMD. For the NAT-2 dataset, the 2-year late AMD prediction accuracy was 84%.ConclusionsValidated color fundus photo-based models for AMD screening and risk prediction for late AMD are now ready for clinical testing and potential telemedical deployment.Translational RelevanceNoninvasive, highly accurate, and fast AI methods to screen for referral level AMD and to predict late AMD progression offer significant potential improvements in our care of this prevalent blinding disease.

Cataract Surgery and the 6-year Incidence of Age-Related Macular Degeneration in a Multiethnic Asian Cohort.

The aim of this study was to determine whether cataract surgery was associated with age-related macular degeneration (AMD) development in Asian patients. Longitudinal cohort study. Participants from the Singapore Malay and Indian Eye Studies were recruited between 2004 and 2015. A total of 6790 late-AMD-free eyes from 3475 individuals were followed for 6 years on average. Multivariable regression analysis using generalized estimating equations determined associations between cataract surgery and the incidence of any, early, and late AMD. The mean age (SD) of participants was 55.5 (9.1) years; 48.1% were male; 11.3% of eyes had cataract surgery recorded; incident any, early, and late AMD developed in 238 (3.6%), 222 (3.4%), and 29 (0.4%) eyes, respectively. Operated eyes had higher incidence of late AMD [1.4% vs 0.3%; adjusted risk ratio (RR): 3.47, 95% confidence interval (CI) 1.40-8.57], but not early AMD (6.0% vs 3.0%, adjusted RR: 1.12, 95% CI 0.76-1.64) or any AMD (6.9 vs 3.2%, adjusted RR: 1.23, 95% CI 0.85-1.78). Our data are consistent with findings in population-based Caucasian studies that cataract surgery may be associated with incidence of late AMD. However, the absolute risk of late AMD development remains low and physicians should continue to balance the benefits and risks of cataract surgery in elderly patients.

OCT Risk Factors for Development of Late Age-Related Macular Degeneration in the Fellow Eyes of Patients Enrolled in the HARBOR Study

To evaluate the relationship between OCT features and progression to late age related-macular degeneration (AMD) in the fellow eyes of patients enrolled in the Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular AMD (HARBOR) (ClinicalTrials.gov identifier, NCT00891735). Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment-controlled clinical trial. Evaluable patients (n= 501) with macular neovascularization (MNV) secondary to neovascular AMD and early or intermediate AMD in the fellow eye. Volume OCT scans from 501 fellow eyes of 501 patients with MNV were reviewed. Baseline OCT features that were assessed included intraretinal hypereflective foci (IHRF), hyporeflective foci (hRF) within drusenoid lesions (DLs), subretinal drusenoid deposits (SDDs), and drusen volume (DV) of 0.03 mm3 or more. OCT images obtained at months 6, 12, 18, and 24 were graded by masked graders for late AMD (defined as MNV, complete retinal pigment epithelium and photoreceptor atrophy [cRORA], or both). Participant demographic characteristics (age, gender, and smoke exposure) and baseline OCT features were correlated with progression to late AMD. Incidence of late AMD, hazard ratio (HR) for demographics, and OCT risk factors. At month 24, 33.13% of eyes (166/501) demonstrated late AMD: 20.96% (105/501) demonstrated cRORA, whereas 12.18% (61/501) demonstrated MNV. Baseline demographic factors were not associated significantly with development of late AMD, whereas significant associations were identified for all OCT features. Intraretinal hypereflective foci had an HR of 5.21 (95% confidence interval [CI], 3.29-8.26), hRF within DLs had an HR of 2.42 (95% CI, 1.74-3.38), SDD had an HR of 1.95 (95% CI, 1.34-2.82), and DV of 0.03 mm3 or more had an HR of 1.46 (95% CI, 1.03-2.07). The correlation remained significant when considering only the progression to cRORA and MNV alone, except for DV, which was not associated significantly with progression to MNV. We confirmed that 4 previously reported OCT risk factors were associated with progression to late AMD in the fellow eyes of patients newly diagnosed with MNV. Although outcomes of more than 2 years were not evaluated, these findings may help to identify high-risk AMD patients.

Serum 25-Hydroxyvitamin D Concentrations and Incidence of Age-Related Macular Degeneration: The Atherosclerosis Risk in Communities Study.

PurposeTo investigate the association between serum 25-hydroxyvitamin D (25[OH]D) concentrations at visit 2 (1990–1992) and the 18-year incidence of age-related macular degeneration (AMD) between visit 3 (1993–1995) and visit 5 (2011–2013).MethodsThis prospective analysis was conducted in a subset of participants (n = 1225) from the Atherosclerosis Risk in Communities Study. We evaluated the incidence of any, early, and late AMD from visit 3 to 5. The 25(OH)D concentrations were assessed in 2012–2013 by using stored serum from visit 2. Retinal fundus photographs taken at both visits were graded side by side to determine the incidence of AMD. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for incident AMD outcomes during 18 years of follow-up (1993–1995 to 2011–2013) by tertile of 25(OH)D adjusted for age, race, and smoking status. P for linear trend was estimated by using continuous 25(OH)D concentrations. Sensitivity analyses applied inverse probability weights to account for selection to have eye photographs, death, and loss to follow-up.ResultsThere was a decreased odds of any incident AMD (n = 139) and large, soft drusen (n = 80) in 25(OH)D tertile 3 versus 1, with OR (95% CI) = 0.57 (0.36–0.90), P trend = 0.11 and with 0.52 (0.28–0.93), P trend = 0.18, respectively. Applying sampling weights attenuated these results to 0.66 (0.38–1.16), P trend = 0.32 (any incident AMD) and 0.54 (0.27–1.09), P trend = 0.36 (large, soft drusen), respectively, suggesting these associations may be biased by loss to follow-up and sampling for retinal photographs at visit 5. No statistically significant results were observed with pigmentary abnormalities (n = 46) or incident late AMD (n = 26).ConclusionsHigh 25(OH)D concentrations, approximately >70 nM, may be associated with decreased odds of incident early AMD.

Consumption of eggs and the 15-year incidence of age-related macular degeneration

A naturally rich source of lutein and zeaxanthin are eggs. There is scarce epidemiological data on the temporal association between total egg consumption and age-related macular degeneration (AMD) incidence. We aimed to establish the prospective and independent association between consumption of eggs with the incidence of AMD over a 15-year follow-up. In this population-based cohort study of 3,654 participants aged 49+years examined at baseline, 2034 participants had complete information on baseline egg consumption and AMD signs over 15 years. AMD was determined from retinal photographs. Egg consumption was assessed using a semi-quantitative food-frequency questionnaire. Total egg intake was calculated through summing up intakes in all forms e.g. boiled, poached, fried, scrambled and/or omelette. We summarized total egg consumption into the following categories: ≤1 egg/week; 2-4 eggs/week; 5-6 eggs/week; and ≥1 egg/day. At baseline, participants who consumed 2-4 eggs/week compared to those who consumed ≤1 egg/week (reference group) had reduced risk of incident late-stage AMD after 15 years: multivariable-adjusted odds ratio, OR, 0.51 (95% confidence intervals, CI, 0.28-0.92). Participants who consumed 2-4 eggs/week versus ≤1 egg/week at baseline had 62% reduced risk of developing neovascular AMD. Among those whose AMD onset was at or before the 10-year follow-up, consumption of 2-4 and 5-6 eggs/week was associated with 54% and 65% reduced risk of incident late AMD, respectively. When analyzed as a dichotomized variable, participants who consumed >1 egg/week versus ≤1 egg/week at baseline, had 46% reduced risk of developing late-stage AMD 15 years later: multivariable-adjusted OR 0.54 (95% CI 0.3-0.90). Non-significant associations were observed between egg consumption and incident early AMD. Our findings suggest that moderate consumption of eggs significantly reduces the risk of developing incident late-stage AMD over 15 years.

Incidence of Age-Related Macular Degeneration in the Central Region of Portugal: The Coimbra Eye Study – Report 5

Purpose: To describe the 6.5-year incidence and progression of age-related macular degeneration (AMD) in a coastal town of central Portugal. Methods: Population-based cohort study. Participants underwent standardized interviews and ophthalmological examination. Color fundus photographs were graded according to the International Classification and Grading System for AMD and ARM. The crude and age-standardized incidence of early and late AMD was calculated, and progression was analyzed. Results: The 6.5-year cumulative incidence of early AMD was 10.7%, and of late AMD it was 0.8%. The incidence of early AMD was 7.2, 13.1 and 17.7% for participants aged 55–64, 65–74 and 75–84 years (p < 0.001). The late AMD incidence was 0.3, 0.9 and 2.8% for the corresponding age groups (p = 0.003). The age-standardized incidence was 10.8% (95% CI, 10.74–10.80%) for early and 1.0% (95% CI, 1.00–1.02%) for late AMD. The incidence of both neovascular AMD and geographic atrophy was 0.4%. Progression occurred in 17.2% of patients. Conclusion: The early AMD incidence in a coastal town of central Portugal was found to be similar to that of major epidemiological studies of European-descent populations; however, the incidence of late AMD was lower, and further analysis on risk factors will be conducted.

Oxidized Low-density Lipoprotein and the Incidence of Age-related Macular Degeneration

To examine the relationship between serum oxidized low-density lipoprotein (ox-LDL) cholesterol and the incidence of age-related macular degeneration (AMD) over a 25-year period in a sample of persons from the population-based Beaver Dam Eye Study (BDES). Observational prospective cohort study. A total of 4972 people from the BDES (aged 43-84 years and living in Beaver Dam, Wisconsin in 1988) seen during at least 1 of 6 examination phases at approximately 5-year intervals between 1988 and2016. A 50% random sample of participants (N= 2468) was selected for ox-LDL measurements. Stored frozen specimens from every examination phase were processed using an enzyme-linked immunosorbent assay from a single batch. All available intervals were included for a person, resulting in 6586 person-visits. Age-related macular degeneration was assessed using the Wisconsin Age-related Maculopathy Grading System, and severity was defined using a 5-step severity scale. The severity of the worse eye at each examination was used for analyses. A multi-state Markov (MSM) model was fit to simultaneously assess the ox-LDL relationship to all AMD transitions, including incidence of any AMD, incidence of late AMD, and worsening and improvement of AMD over the 25 years of the study. The mean (standard deviation) level of ox-LDL was 75.3 (23.1) U/L at the baseline examination. When adjusting for age, sex, ARMS2 and CFH risk alleles, and examination phase, the ox-LDL at the beginning of a period was not statistically significantly associated with the incidence of any AMD (hazard ratio per 10 U/L ox-LDL was 1.03, 95% confidence interval 0.98,1.09). Furthermore, ox-LDL was not associated with worsening anywhere along the AMD severity scale, nor with incidence of late AMD. The lack of relationships of ox-LDL to the incidence of any AMD or worsening of AMD remained after adjustment for history of statin use, smoking status, body mass index, and history of cardiovascular disease (data not shown). Our findings do not provide evidence for statistically significant relationships between ox-LDL and AMD disease development or worsening of AMD.

Association of Dietary Nitrate Intake with the 15-Year Incidence of Age-Related Macular Degeneration

BackgroundDietary nitrate, found predominantly in green leafy vegetables and beetroot, is a precursor of nitric oxide. Under- or overproduction of nitric oxide is implicated in the etiology of several eye diseases. However, the potential influence of dietary nitrate intake on age-related macular degeneration (AMD) risk has not been assessed. ObjectiveTo investigate the temporal association between dietary nitrate intake (from both vegetable and nonvegetable sources) and the 15-year incidence of AMD, independent of potential confounders. DesignA longitudinal cohort study conducted from 1992-1994 to 2007-2009. Participants/settingThe Blue Mountains Eye Study is a population-based study of adults aged 49+ at baseline, from a region west of Sydney, Australia. At baseline, 2,856 participants with complete dietary data and AMD information were examined, and of these, 2,037 participants were re-examined 15 years later and thus included in incidence analysis. Main outcomes measuredIncidence of AMD (main outcome) was assessed from retinal photographs. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. Nitrate intake from vegetables and nonvegetable sources was calculated by use of a validated comprehensive database. ResultsAfter adjusting for age, sex, smoking, energy intake, fish consumption, and AMD risk alleles (complement factor H and age-related maculopathy susceptibility-2 single nucleotide polymorphisms), participants in the third quartile compared with those in the first quartile (reference group) of total nitrate and total vegetable nitrate intake had reduced risk of incident early AMD: odds ratio (OR) 0.61 (95% CI 0.41 to 0.90) and OR 0.65 (95% CI 0.44 to 0.96), respectively. Significant associations were not observed between the fourth vs first quartile of total nitrate and vegetable nitrate intake with incident early AMD: OR 0.74 (95% CI 0.51 to 1.08) and OR 0.69 (95% CI 0.47 to 1.00), respectively. Nonsignificant associations were also observed with 15-year incidence of late AMD and total nonvegetable nitrate intake. ConclusionsThese novel findings could have important implications, if the association between total nitrate intake and vegetable nitrate intake and 15-year incidence of early AMD is confirmed in other observational or intervention studies.

Dietary flavonoids and the prevalence and 15-y incidence of age-related macular degeneration

The majority of research performed to date has examined the effects of commonly known antioxidants such as vitamins C, E, and A and carotenoids on age-related macular degeneration (AMD) risk and progression. To date, there is limited research on promising phytochemicals with antioxidant and anti-inflammatory properties, including flavonoids. In this exploratory study, we aimed to assess the independent associations between dietary intake of total flavonoids and common flavonoid classes with the prevalence and 15-y incidence of AMD. In this population-based cohort study, 2856 adults aged ≥49 y at baseline and 2037 followed up 15 y later were included in prevalence and incidence analyses, respectively. Dietary intake was assessed by using a semiquantitative food-frequency questionnaire (FFQ). Estimates of the flavonoid content of foods in the FFQ were assessed by using the USDA Flavonoid, Isoflavone, and Proanthocyanidin databases. AMD was assessed from retinal photographs. In cross-sectional analysis, each 1-SD increase in total overall flavonoid intake was associated with a reduced likelihood of any AMD (multivariable-adjusted OR: 0.76; 95% CI: 0.58, 0.99). Each 1-SD increase in dietary intake of total flavonols and total flavanones was associated with reduced odds of the prevalence of any AMD [multivariable-adjusted OR (95% CI): 0.75 (0.58, 0.97) and 0.77 (0.60, 0.99), respectively]. A marginally significant trend (P=0.05) was observed between increasing the intake of total flavanone and hesperidin (from the first to the fourth quartile) and reduced likelihood of incident late AMD, after multivariable adjustment. Participants who reported ≥1 serving of oranges/d compared with those who never consumed oranges at baseline had a reduced risk of late AMD 15 y later (multivariable-adjusted OR: 0.39; 95% CI: 0.18, 0.85). Our findings suggest an independent and protective association between dietary intake of flavonoids and the likelihood of having AMD. Additional prospective cohort studies are needed to validate these findings.

Six-Year Incidence of Age-Related Macular Degeneration in Asian Malays: The Singapore Malay Eye Study

To determine the 6-year incidence of early and late age-related macular degeneration (AMD) in a Singaporean Malay population and to validate the Age-Related Eye Disease Study (AREDS) simplified severity scale in Asians. Prospective, population cohort study. The Singapore Malay Eye Study baseline participants (age, ≥40 years; 2006-2008) were followed up in 2011 through 2013, and 1901 of 3280 of eligible participants (72.1%) took part. Fundus photographs were graded using the Wisconsin AMD grading system. Incidence of early and late AMD. Gradable fundus photographs were available for 1809 participants who attended both baseline and 6-year follow-up examinations. The age-standardized incidences of early and late AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42-1.29), respectively. The 5-year age-standardized incidence of early AMD (calculated based on the 6-year incidence) was lower in our population (5.58%; 95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The incidence of late AMD in our population was similar to that of the Beaver Dam Eye Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4, 9.09%). This study documented the incidence of early and late AMD in a Malay population. The AREDS simplified severity scale is useful in predicting the risk of late AMD development in Asians.

Evaluating the Validity of the Age-Related Eye Disease Study Grading Scale for Age-Related Macular Degeneration: AREDS2 Report 10.

To test potential treatments for age-related macular degeneration (AMD), clinical trials need standardized outcome measures that are valid for predicting AMD progression in different study populations. To evaluate the validity of the Age-Related Eye Disease Study (AREDS) detailed and simple AMD severity scales by comparing rates of development of late AMD (neovascular AMD and/or central geographic atrophy) between AREDS and AREDS2 participants. Both AREDS (1992-2001) and AREDS2 (2006-2012) enrolled patients from academic and community-based retinal practices across the United States. In AREDS (n = 4519), participants with varying severity of AMD-from no AMD to late AMD in 1 eye-were enrolled. In AREDS2 (n = 4203), participants with bilateral large drusen or large drusen in the study eye and late AMD in the fellow eye were enrolled. Five-year incidence of late AMD, assessed by annual masked centralized fundus photograph grading. In AREDS, the mean (SD) age of the patients was 69.3 (5.7) years, and 2519 (55.7%) were female. In AREDS2, the mean (SD) age of the patients was 73.1 (7.7) years, and 2388 (56.8%) were female. The 5-year rates of late AMD did not differ between AREDS2 and AREDS participants within nearly all baseline AMD detailed severity scale levels: levels 1 to 3: 2.4% vs 0.5% (difference, 1.9%; 95% CI, -0.2% to 4.0%; P < .001); level 4: 6.5% vs 4.9% (difference, 1.6%; 95% CI, -1.7% to 4.8%; P = .34); level 5: 8.0% vs 5.6% (difference, 2.4%; 95% CI, -1.2% to 5.9%; P = .22); level 6: 12.8% vs 13.7% (difference, -0.9%; 95% CI, -4.8% to 3.1%; P = .66); level 7: 26.2% vs 27.8% (difference, -1.5%; 95% CI, -6.6% to 3.5%; P = .54); and level 8: 46.4% vs 44.7% (difference, 1.7%; 95% CI, -7.5% to 10.9%; P = .72). Within simple scale levels, AREDS2 and AREDS 5-year rates did not differ significantly except for level 1 (9.4% vs 3.1%, P = .02; level 2: 12.8% vs 11.8%, P = .65; level 3: 26.3% vs 25.9%, P = .90; and level 4: 45.6% vs 47.3%, P = .57). The AREDS detailed and simple AMD severity scales were useful measures for assessing the risk of developing late AMD in the AREDS2 population; these data suggest that they should be useful tools for clinical trials of AMD treatments.

Validating the AREDS Simplified Severity Scale of Age-Related Macular Degeneration with 5- and 10-Year Incident Data in a Population-Based Sample

Most classification systems for age-related macular degeneration (AMD) were developed from patients in clinical trials. We aimed to validate the Age-Related Eye Diseases Study (AREDS) simplified severity scale of AMD classification using 5- and 10-year incident late AMD data from the population-based Blue Mountains Eye Study (BMES) cohort. Comparative study of population-based cohort and clinical trial. Blue Mountains Eye Study participants 40 to 97 years of age at baseline (n= 2134) and AREDS participants 55 to 80 years of age (n= 3640). In the BMES, AMD lesions were graded from stereoscopic color photographs and were classified according to the AREDS simplified severity scale. The AREDS simplified scale calculates a risk score based on the number of early AMD risk factors (large drusen and pigment abnormalities) in both eyes that can range from 0 to4. Five- and 10-year incident late AMD (presence of geographic atrophy or choroidal neovascularization). The AREDS simplified scale performed similarly when applied to both the BMES population-based participants and the AREDS clinical trial-based participants in predicting 5- and 10-year incidence of late AMD. For scores 0 to 4, the 5-year incidence rates for the BMES compared with the AREDS were 0.2% versus 0.4%, 3.1% versus 3.1%, 12.1% versus 11.8%, 13.5% versus 25.9%, and 47.1% versus 47.3%, respectively. The corresponding 10-year incidence rates for the BMES compared with the AREDS were 0.7% versus 1.5%, 7.3% versus 8.4%, 36.6% versus 27.6%, 20.0% versus 52.7%, and 75.0% versus 71.4%, respectively. The AREDS simplified severity scale classified late AMD risk levels similarly when applied to population-based and clinical trial samples. These results support the robustness of the AREDS simplified severity scale.

Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials

To evaluate the association between pseudodrusen and incidence of late age-related macular degeneration (AMD) in fellow eyes of patients with unilateral neovascular AMD (nAMD). Cohort study within the Comparison of AMD Treatments Trials (CATT). Patients with neither nAMD nor geographic atrophy (GA) in the fellow eye at baseline. Presence and type (dot, reticular, or confluent) of baseline pseudodrusen were assessed using digital color fundus photography (CFP) viewed under full color, green channel, and blue channel; red-free images; and fluorescein angiography (FA). Incidence of nAMD was based on monthly clinical examination and reading center evaluation of images at years 1 and 2. Incidence of GA was based on reading center evaluation of CFP and FA images at years 1 and 2. Associations of baseline pseudodrusen with incident nAMD and GA were summarized with adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs) from multivariate Cox models, with adjustment of covariates identified through backward stepwise selection. Incident nAMD and GA. Among 620 fellow eyes, 176 (28.4%) had baseline pseudodrusen (55% dot, 82% reticular, 35% confluent). Within 2 years, nAMD occurred in 54 eyes (30.7%) with pseudodrusen and in 72 eyes (16.2%) without pseudodrusen (aRR, 2.05; 95% CI, 1.43-2.93); GA occurred in 27 eyes (15.3%) with pseudodrusen and in 37 eyes (8.3%) without pseudodrusen (aRR, 1.89; 95% CI, 1.13-3.17); late AMD occurred in 73 eyes (41.5%) with pseudodrusen and in 101 eyes (22.8%) without pseudodrusen (aRR, 2.07; 95% CI, 1.51-2.83). Dot pseudodrusen were associated independently with nAMD (aRR, 2.53; 95% CI, 1.60-4.00), whereas confluent pseudodrusen were associated independently with GA (aRR, 4.35; 95% CI, 1.69-11.2). Eyes with pseudodrusen had increased incidence of late AMD regardless of whether the Age-Related Eye Diseases Study (AREDS) severity score was 2 (28.7% vs. 10.3%), 3 (34.9% vs. 13.7%), or 4 (50.5% vs. 32.0%). In fellow eyes of CATT participants, pseudodrusen were associated independently with a higher incidence of both nAMD and GA. Dot pseudodrusen were associated with nAMD, whereas confluent pseudodrusen were associated with GA. Pseudodrusen should be considered along with the AREDS severity score for predicting late AMD.

Overweight, Obesity, and Risk of Age-Related Macular Degeneration.

The aim of this study was to quantify the relationship between categories of body mass index (BMI) and age-related macular degeneration (AMD) risk in different stages. MEDLINE, EMBASE, and ISI Web of Science were searched for all eligible studies on the relationship between BMI and incident early or late AMD. The analyses were based on data extracted from study reports. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of this association, and dose-response relationship was assessed by restricted cubic spline. Seven prospective cohort studies with 1613 cases identified among 31,151 subjects were included. For overweight, the relationship remained insignificant for its association with both early AMD (RR = 0.92, 95% CI: 0.68-1.15; P = 0.54) and late AMD (RR = 1.09, 95% CI: 0.93-1.25; P = 0.18). A marked 32% increase in the risk of developing late AMD was noted among obese individuals (RR = 1.32, 95% CI: 1.11-1.53, P < 0.01), while obesity showed no significant association with early AMD (RR = 0.91, 95% CI: 0.74-1.08; P = 0.67). Furthermore, elevated BMI showed a linear dose-response relation with AMD risk (Pnonlinearity = 0.17), and the AMD risk increased by 2% (RR = 1.02, 95% CI: 1.01-1.04) for each 1 kg/m2 increase in BMI within the overweight and obese BMI ranges. Excess body weight was weakly associated with increase in the risk of AMD in a dose-dependent fashion, especially for its late stage, indicating that keeping normal body weight and avoiding further weight gain may confer potential protection against this disease.