Risk Factors for Five-Year Incident Age-related Macular Degeneration: The Reykjavik Eye Study

doi:10.1016/j.ajo.2006.04.015

American Journal of Ophthalmology

Volume 142, Issue 3, September 2006, Pages 419-428.e1

https://doi.org/10.1016/j.ajo.2006.04.015 Get rights and content

Purpose

To establish risk factors for five-year incidence of age-related macular degeneration (AMD).

Design

Population-based, prospective cohort study, and risk analysis.

Methods

A random sample from the Reykjavik Population Census for individuals 50 years and older was selected. We took fundus stereo color photographs and used standard grading system to study the five-year incidence of drusen, pigmentary abnormalities, and AMD and to examine possible risk factors. A questionnaire including information on disease, medication, diet, and lifestyle from the Reykjavik Eye Study database provided additional information.

Results

Current alcohol consumption decreased the risk for drusen. Being married rather than divorced or widowed decreased the risk for soft drusen; being single decreased the risk of hypopigmentation as compared with being divorced or married. Both consuming dietary fiber–rich vegetables and meat and meat products once a week or less frequently was a risk factor for developing soft drusen and decreased the risk of pigmentary abnormalities. Those who had smoked 20 pack-years or more as compared with nonsmokers had decreased survival rate over the five years (odds ratio (OR) 0.46, 95% confidence interval (CI) 0.27 to 0.80; P = .006).

Conclusions

Risk factors for drusen appear to differ from risk factors for pigmentary abnormalities. The effect of smoking on developing AMD is partly masked by selective mortality.

Section snippets

Methods

The Reykjavik Eye Study is a population-based prospective cohort study of age-related eye disease. Detailed description of grading methods, κ values, and quality assurance for ARM can be found in our previous articles on prevalence⁷ and five-year incidence of AMD.⁸ Ethical approval was obtained from the Data Protection Commission and the National Bioethics Committee in Iceland in accordance with the guidelines of the Helsinki Declaration. The National Bioethics Committee also acts as

Results

The annual risk of developing ARM changes is shown in Table 2. The average increase in risk for every one year after the age of 50 years is 7% to 9% for drusen, and 5% to 9% for pigmentary abnormalities. The average increase in risk for each year after 50 years is 21% for geographic atrophy. Similar analysis could not be performed for exudative AMD because only one person developed exudative AMD during the five years.

We calculated ORs for smoking using “ever” vs “never” smoker. We also analyzed

Discussion

The strengths of the current study are the high percentage of patients who were reexamined after five years, the fact that this is a random sample, and the consistency of data-gathering and grading techniques, as well as the fact that every person was examined within two months at baseline and again exactly five years later. The two data sets were graded within six months of each other by the same graders. The main weaknesses are relatively low study power, especially with regard to late AMD,

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Cited by (70)

Dietary omega-3 polyunsaturated fatty acids and fish intake and risk of age-related macular degeneration
2021, Clinical Nutrition
Epidemiologic studies are inconsistent regarding the association of dietary omega-3 polyunsaturated fatty acids (PUFA) and/or fish intake with risk of age-related macular degeneration (AMD) incidence and progression. The objective was to determine these associations by conducting a meta-analysis of available studies.
Three electronic databases were searched for studies that quantified dietary omega-3 PUFA and/or fish intake from inception to December 2020 without language restriction. Three investigators independently assessed for inclusion and extracted data. Study-specific risk estimates were combined using random-effects model. Potential dose–response associations were explored with the use of generalized least-squares trend estimation.
21 studies were included in the meta-analysis. Higher dietary intakes of omega-3 PUFA was significantly associated with 14% (relative risk [RR]: 0.86, 95% confidence interval [CI]: 0.77, 0.96) and 29% (RR: 0.71, 95% CI: 0.55, 0.91) lower risk of early and late AMD, respectively. The dose–response analysis showed a 6% and 22% decrease in the risk of early and late AMD for each additional 1 g/d omega-3 PUFA intake. For individual omega-3 PUFA, the intake of eicosapentaenoic acid and docosahexaenoic acid was inversely associated with lower AMD risk, whereas no association was found for the alpha-linolenic acid. Consistent inverse associations were also found between fish intake and AMD. The pooled RRs comparing extreme categories of fish intake were 0.79 (95% CI: 0.70, 0.90) and 0.71 (95% CI: 0.60, 0.85) for early and late AMD risk, respectively. Every 15 g/d of fish consumption was associated with 13% and 14% lower early and late AMD. In addition, fish intake was associated with a significantly reduced risk of AMD progression (RR: 0.73, 95% CI: 0.53, 1.00).
A high intake of dietary omega-3 PUFA or fish was associated with a reduced risk of developing of AMD, which further supports that consumption of omega-3 PUFA-rich foods may be a new avenue nutritional approach to preventing AMD.
A new perspective on lipid research in age-related macular degeneration
2018, Progress in Retinal and Eye Research
There is an urgency to find new treatment strategies that could prevent or delay the onset or progression of AMD. Different classes of lipids and lipoproteins metabolism genes have been associated with AMD in a multiple ways, but despite the ever-increasing knowledge base, we still do not understand fully how circulating lipids or local lipid metabolism contribute to AMD. It is essential to clarify whether dietary lipids, systemic or local lipoprotein metabolismtrafficking of lipids in the retina should be targeted in the disease. In this article, we critically evaluate what has been reported in the literature and identify new directions needed to bring about a significant advance in our understanding of the role for lipids in AMD. This may help to develop potential new treatment strategies through targeting the lipid homeostasis.
Dietary Intakes of Eicosapentaenoic Acid and Docosahexaenoic Acid and Risk of Age-Related Macular Degeneration
2017, Ophthalmology
Citation Excerpt :
Among existing studies of the relation between intakes of long-chain n3 fatty acids or fish with early/intermediate AMD, 233,34 of 4 cross-sectional studies33–36 reported an inverse association, whereas 1 case-control study did not.37 In all 3 prospective cohort studies an inverse association was found.10–12 In particular, the 10-year prospective Women's Health Study, which has a similar study methodology to ours (e.g., a cohort of female health professionals, the same Willett FFQs and classification of AMD types)11 showed similar results (HR, 0.62, 95% CI, 0.44–0.86, for intake of DHA comparing tertile 3 [median, 230 mg/day] with tertile 1 [median, 60 mg/day]).
To evaluate the associations between intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the intermediate and advanced stages of age-related macular degeneration (AMD).
Prospective cohort study.
We followed 75 889 women from the Nurses' Health Study and 38 961 men from the Health Professionals Follow-Up Study who were at least 50 years old, from 1984 to 2012 and 1986 to 2010, respectively. Cohort participants are mostly white (≥95%).
We assessed dietary intake by a validated food frequency questionnaire (FFQ) at baseline and every 4 years. We calculated cumulative average intakes of EPA and DHA from FFQs and also computed predicted erythrocyte and plasma scores directly from food intake using regression models. Cox proportional hazards models were used to compute the associations with AMD outcomes.
We confirmed 1589 incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse, owing primarily to AMD, by medical record review.
For intermediate AMD, the pooled hazard ratio (HR) between the 2 cohorts for DHA comparing the extreme quintiles of intake was 0.78 (95% confidence interval [CI], 0.66–0.92; P trend, 0.008) and for EPA + DHA was 0.83 (95% CI, 0.71–0.98; P trend, 0.03). The pooled HR for fatty fish, comparing ≥5 servings per week to almost never, was 0.61 (95% CI, 0.46–0.81; P trend, <0.001). For advanced AMD, the pooled HR for DHA was 1.01 (95% CI, 0.84–1.21; P trend, 0.75) and for fatty fish was 0.80 (95% CI, 0.59–1.08; P trend, 0.11). Secondary analyses using predicted erythrocyte and plasma scores of EPA and DHA yielded slightly stronger inverse associations for intermediate AMD and similar results for advanced AMD.
Higher intakes of EPA and DHA may prevent or delay the occurrence of visually significant intermediate AMD. However, the totality of current evidence for EPA and DHA and advanced AMD is discordant, though there was no association with advanced AMD in the present study.
Diet and supplements in the prevention and treatment of eye diseases
2017, Nutrition in the Prevention and Treatment of Disease
Nutritional issues in vision health are no longer limited to preventing deficiencies. Over the past 25 years, a large body of evidence has emerged suggesting that vitamin supplements could play a role in treating ocular diseases resulting from genetic mutations, and that diet may slow the progression of diabetic retinopathy and common eye diseases, such as age-related cataract, age-related macular degeneration (AMD), and glaucoma. The eye diseases appear to be, in part, ocular manifestations of broader systemic metabolic stress, oxidative stress, and inflammation. However, there are some unique nutritional needs of eye tissues. These include the dietary carotenoids lutein (and isomers) which selectively and exclusively accumulate in the retina, lens, and many other ocular tissues. These carotenoids improve vision and protect against light damage by absorbing blue wavelengths of light and may also reduce inflammation. Antioxidants (vitamin C and E, lutein, and other eye carotenoids) present in high concentrations in certain ocular tissues play a role in protecting against photooxidative damage. Recent evidence has also emerged to suggest a role of lutein during gestation and infancy. Human milk appears to be a bioavailable source of lutein, but adding of lutein to infant formula is not routine. Setting optimal and safe ranges of intake in infants and pregnant and lactating mothers is an important direction of future research. Zinc is also highly concentrated in the retina and plays multiple roles in eye health. Supplementation with high-dose antioxidants and zinc is considered a standard of care for slowing the progression of AMD. Currently, there is no strong evidence that these or other supplements prevent this disease, or other age-related eye diseases. However, the current body of evidence does suggest that balanced, fruit and vegetable-rich diets are the most prudent means of lowering risk for age-related eye disease and optimizing vision function throughout life.
Five-year incidence, progression, and risk factors for age-related macular degeneration: The age, gene/environment susceptibility study
2014, Ophthalmology
Citation Excerpt :
Several factors reported by some other studies as risk indicators, including hypertension, diabetes, total cholesterol, triglycerides, and omega-3 fatty acids/cod liver oil, were investigated in our analysis and were found to be unrelated to AMD status after considering age, sex, and smoking. Icelanders commonly consume cod liver daily, in addition to having a high intake of fish and fish products.42 Studies from populations where consumption of fish and fish products is much less common have reported omega-3 fatty acids to be protective against the development of early AMD, although findings from a recent clinical trial did not confirm this supposition.43,44
To investigate the incidence and progression of age-related macular degeneration (AMD) and associated risk factors.
Population-based, prospective, cohort study.
We included 2868 participants from the Age Gene/Environment Susceptibility-Reykjavik Study with retinal data at baseline and 5-year follow-up.
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.
We assessed AMD, defined as early or late.
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/m²; 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).
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.
Dietary patterns and their associations with age-related macular degeneration: The Melbourne collaborative cohort study
2014, Ophthalmology
To evaluate the association between dietary patterns and age-related macular degeneration (AMD).
Food frequency data were collected from Melbourne Collaborative Cohort Study (MCCS) participants at the baseline study in 1990–1994. During follow-up in 2003–2007, retinal photographs were taken and evaluated for AMD.
At baseline, 41 514 participants aged 40 to 70 years and born in Australia or New Zealand (69%), or who had migrated from the United Kingdom, Italy, Greece, or Malta (31%) were recruited. Of these, 21 132 were assessed for AMD prevalence at follow-up.
Principal component analysis was used to identify dietary patterns (Factors F1–6) among the food items. Logistic regression was used to assess associations of dietary patterns with AMD.
Odds ratios (ORs) for early stages and advanced AMD in association with dietary patterns.
A total of 2508 participants (12.8%) had early stages of AMD, and 108 participants (0.6%) had advanced AMD. Six factors characterized by predominant intakes of fruits (F1); vegetables (F2); grains, fish, steamed or boiled chicken, vegetables, and nuts (F3); red meat (F4); processed foods comprising cakes, sweet biscuits, and desserts (F5); and salad (F6) were identified. Higher F3 scores were associated with a lower prevalence of advanced AMD (fourth vs. first quartile) (OR, 0.49; 95% confidence interval [CI], 0.28–0.87), whereas F4 scores greater than the median were associated with a higher prevalence of advanced AMD (OR, 1.46; 95% CI, 1.0–2.17).
Rather than specific individual food items, these factors represent a broader picture of food consumption. A dietary pattern high in fruits, vegetables, chicken, and nuts and a pattern low in red meat seems to be associated with a lower prevalence of advanced AMD. No particular food pattern seemed to be associated with the prevalence of the earliest stages of AMD.

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Supported in part by open Grants (all to F.J.) from St Joseph’s Hospital, Landakot Foundation, Reykjavik, Iceland; University National Hospital and University of Iceland Research Grant; and Helga Jonsdottir and Sigurlidi Kristjansson Memorial Research Fund.

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Original articleRisk Factors for Five-Year Incident Age-related Macular Degeneration: The Reykjavik Eye Study

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Surv Ophthalmol

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

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The prevalence of age-related maculopathy in Icelandthe Reykjavik Eye Study

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The risk and natural course age-related maculopathyfollow up at 6½ years in the Rotterdam Study

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Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration

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Risk factors for the incidence of advanced age-related macular degeneration in the Age-Related Eye Disease Study (AREDS). AREDS Report 19

Ophthalmology

Smoking and age-related macular degenerationthe number of pack-years of cigarette smoking is a major determinant for risk of both geographic atrophy and choroidal neovascularization

Br J Ophthalmol

Original article
Risk Factors for Five-Year Incident Age-related Macular Degeneration: The Reykjavik Eye Study