Age-Related Macular Degeneration: A Review.

Importance: Age-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older people and is expected to affect approximately 288 million people worldwide by 2040. Observations: Older age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD. AMD occurs when extracellular deposits accumulate in the outer retina, ultimately leading to photoreceptor degeneration and loss of central vision. The late stages of AMD are characterized by outer retinal atrophy, termed geographic atrophy, or neovascularization associated with subretinal and/or intraretinal exudation, termed exudative neovascular AMD. The annual incidence of AMD ranges from 0.3 per 1000 in people who are aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older. The estimated heritability of late-stage AMD is approximately 71% (95% CI, 18%-88%). Long-term prospective cohort studies show a significantly higher AMD incidence in people who smoke more than 20 cigarettes per day compared with people who never smoked. AMD is diagnosed primarily with clinical examination that includes a special lens that focuses light of the slit lamp through the pupil. Exudative neovascular AMD is best identified using angiography and by optical coherence tomography. Individuals with AMD who take nutritional supplements consisting of high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability to progress to late-stage AMD at 5 years vs a 28% probability for those taking a placebo. In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections experience less than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving sham treatment. Conclusions and Relevance: The prevalence of AMD is anticipated to increase worldwide to 288 million individuals by 2040. Intravitreally administered anti-VEGF treatment is first-line therapy for exudative neovascular AMD.

[Nutrition and age-related macular degeneration]. / Nutrition et dégénérescence maculaire liée à l'âge.

Age-related macular degeneration (AMD) is the leading cause of vision loss in France and in other industrialized countries. AMD affects around 20 % of the population over the age of 80 years. This complex and multifactorial disease involves both genetic susceptibility and environmental factors. Smoking and nutrition are well-known modifiable risk factors for AMD. Numerous studies provide convincing arguments in favor of micronutrients to encourage dietary advice and the prescription of nutritional supplements containing antioxidant vitamins, lutein and omega-3 fatty acids. Attention to modifiable risk factors is of utmost importance to reduce progression to advanced AMD and associated medical and societal burdens.

Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review. OBJECTIVES: To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers, most recently on 29 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation to placebo or no intervention, in people with AMD. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. MAIN RESULTS: We included 26 studies conducted in the USA, Europe, China, and Australia. These studies enroled 11,952 people aged 65 to 75 years and included slightly more women (on average 56% women). We judged the studies that contributed data to the review to be at low or unclear risk of bias. Thirteen studies compared multivitamins with control in people with early and intermediate AMD. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 3 studies, 2445 participants; moderate-certainty evidence). In people with early AMD, who are at low risk of progression, this means there would be approximately four fewer cases of progression to late AMD for every 1000 people taking vitamins (one fewer to six fewer cases). In people with intermediate AMD at higher risk of progression, this corresponds to approximately 78 fewer cases of progression for every 1000 people taking vitamins (26 fewer to 126 fewer). AREDS also provided evidence of a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence), and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (measured with the Visual Function Questionnaire) in treated compared with non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). In exploratory subgroup analyses in the follow-on study to AREDS (AREDS2), replacing beta-carotene with lutein/zeaxanthin gave hazard ratios (HR) of 0.82 (95% CI 0.69 to 0.96), 0.78 (95% CI 0.64 to 0.94), 0.94 (95% CI 0.70 to 1.26), and 0.88 (95% CI 0.75 to 1.03) for progression to late AMD, neovascular AMD, geographic atrophy, and vision loss, respectively. Six studies compared lutein (with or without zeaxanthin) with placebo and one study compared a multivitamin including lutein/zeaxanthin with multivitamin alone. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA; almost all participants in AREDS2 also took the original AREDS supplementation formula. People taking lutein/zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05) compared with control (1 study, 4176 participants, 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein/zeaxanthin and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (Visual Function Questionnaire) was similar between groups (MD 1.21, 95% CI -2.59 to 5.01; 2 studies, 308 participants; moderate-certainty evidence). One study in Australia randomised 1204 people to vitamin E or placebo with four years of follow-up; 19% of participants had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05; very low-certainty evidence). There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47; low-certainty evidence). There were no data on neovascular AMD, geographic atrophy, or quality of life. Five studies compared zinc with placebo. Evidence largely drawn from the largest study (AREDS) found a lower progression to late AMD over six years (OR 0.83, 95% CI 0.70 to 0.98; 3 studies, 3790 participants; moderate-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 2 studies, 3791 participants; moderate-certainty evidence). There were no data on quality of life. Gastrointestinal symptoms were the main reported adverse effect. In AREDS, zinc was associated with a higher risk of genitourinary problems in men, but no difference was seen between high- and low-dose zinc groups in AREDS2. Most studies were too small to detect rare adverse effects. Data from larger studies (AREDS/AREDS2) suggested there may be little or no effect on mortality with multivitamin (HR 0.87, 95% CI 0.60 to 1.25; low-certainty evidence) or lutein/zeaxanthin supplementation (HR 1.06, 95% CI 0.87 to 1.31; very low-certainty evidence), but confirmed the increased risk of lung cancer with beta-carotene, mostly in former smokers. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows down progression to late AMD. People with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, exploratory subgroup analyses from one large American study support the view that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula.

Dietary habits and dietary nutrient intake in patients with age-related macular degeneration: A case-control study.

OBJECTIVES: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older adults in developed countries. Although many risk factors are known, the pathogenesis of AMD is still unclear. However, oxidative stress probably plays a vital role in the process of AMD. The increasing prevalence of AMD, risk of vision loss, limited treatment of dry form, expensive treatment of wet form, and decreased quality of life are factors that lead to considering modifiable risk factors of AMD, such as nutrition. This is the first study describing the relationship between dietary habits, dietary nutrient intake and AMD in the Czech Republic. METHODS: In this research, a total of 93 cases with AMD and 58 controls without AMD and cataracts participated. All participants were ophthalmologically examined at the Clinic of Eye Treatments at the University Hospital Brno. Data were collected using a pre-tested self-report questionnaire in a face-to-face interview. Food consumption frequency was assessed by an 18-item semiquantitative food-frequency questionnaire (FFQ). Dietary nutrient intakes were calculated from a 24-hour recall. RESULTS: Patients with AMD compared with controls had significantly higher consumption of legumes and lower consumption of meat products, salt and salty products. In men, we found statistically significant differences in alcohol consumption. The case group consumed alcoholic beverages more frequently (median: 2 times a week) than the control group (median: 1-3 times a month). No differences in alcohol consumption were found in women. In comparison to the case group, the control group had a significantly higher dietary intake of energy (5,783.8 vs. 4,849.3 kJ/day; p = 0.002), proteins (65.3 vs. 52.3 g/day; p = 0.002), fats (57.6 vs. 49.4 g/day; p = 0.046), saturated fatty acids (21.7 vs. 18.9 g/day; p = 0.026), carbohydrates (150.4 vs. 127.1 g/day; p = 0.017), dietary fibre (13.2 vs. 11.3 g/day; p = 0.044), vitamin B2 (1.0 vs. 0.9 mg/day; p = 0.029), vitamin B3 (13.9 vs. 10.0 mg/day; p = 0.011), pantothenic acid (3.5 vs. 2.8 mg/day; p = 0.001), vitamin B6 (1.3 vs. 1.0 mg/day; p = 0.001), potassium (1,656.5 vs. 1,418.0 mg/day; p = 0.022), phosphorus (845.4 vs. 718.7 mg/day; p = 0.020), magnesium (176.5 vs. 143.0 mg/day; p = 0.012), copper (1.0 vs. 0.8 mg/day; p = 0.011), and zinc (7.1 vs. 6.1 mg/day; p = 0.012) counted from a 24-hour recall. CONCLUSIONS: According to FFQ, dietary habits in the patients with AMD and controls were similar. In men from the case group, we found statistically significant higher alcohol consumption. According to a 24-hour recall, the controls achieved recommended dietary intakes rather than cases. In comparison to the case group, the control group had a significantly higher dietary intake of energy, proteins, fats, saturated fatty acids, carbohydrates, dietary fibre, vitamin B2, vitamin B3, pantothenic acid, vitamin B6, potassium, phosphorus, magnesium, copper, and zinc.

Increased risk of Parkinson's disease amongst patients with age-related macular degeneration and visual disability: A nationwide cohort study.

BACKGROUND AND PURPOSE: The association between Parkinson's disease (PD) and age-related macular degeneration (AMD) has been shown in previous reports. However, the association between the severity of AMD and PD development is unknown. The aim was to evaluate the association of AMD with/without visual disability (VD) with the risk of PD occurrence using the National Health Insurance data in South Korea. METHODS: A total of 4,205,520 individuals, 50 years or older and without a previous diagnosis of PD, participated in the Korean National Health Screening Program in 2009. AMD was verified using diagnostic codes, and participants with VD were defined as those with loss of vision or visual field defect as certified by the Korean Government. The participants were followed up until 31 December 2019, and incident cases of PD were identified using registered diagnostic codes. The hazard ratio was calculated for groups (control and AMD with/without VD) using multivariable adjusted Cox regression analysis. RESULTS: In total, 37,507 participants (0.89%) were diagnosed with PD. Amongst individuals with AMD, the risk of PD development was higher in individuals with VD (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.09-1.67) than in those without (aHR 1.22, 95% CI 1.15-1.30) compared with controls. Additionally, an increased risk of PD was observed in individuals with AMD compared with controls, regardless of the presence of VD (aHR 1.23, 95% CI 1.16-1.31). CONCLUSIONS: Visual disability in AMD was associated with the development of PD. This suggests that neurodegeneration in PD and AMD may have common pathways.

The Relationship between Dietary Calcium and Age-Related Macular Degeneration.

BACKGROUND: Mineral element supplements are widely used in the older adult population. However, little is known of their impact on the progression of age-related macular degeneration (ARMD). The aim of this study was to examine the association between dietary micronutrients and ARMD in older adults. METHODS: We enrolled 5227 participants from the National Health and Nutrition Examination Survey (NHANES 2005-2008) in this cross-sectional study. ARMD was evaluated using an ophthalmic digital imaging system and digital camera. Mineral element consumption was collected using a 24-hour dietary recall. The association between mineral element use and the presence of ARMD was determined by multivariable logistic regression. RESULTS: After adjusting for relevant variables, dietary calcium was negatively associated with ARMD (OR: 680, 95%CI: 0.482-0.960). In contrast to dietary form, serum concentration of calcium was not associated with ARMD. Moreover, increased dietary calcium was associated with reduced ARMD (OR: 0.684, 95%CI: 0.468-1.000). CONCLUSION: A lower consumption of dietary calcium was significantly associated with a higher risk of ARMD. Further longitudinal studies are necessary to explore these findings.

Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28.

Importance: After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up. Objective: To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD). Design, Setting, and Participants: This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022. Interventions: During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively. Main Outcomes and Measures: Self-reported lung cancer and late AMD validated with medical records. Results: This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48). Conclusions and Relevance: Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.

Dietary omega-3 LCPUFA intake in the prevention of neovascular age-related macular degeneration: a systematic review and meta-analysis.

Introduction: Purpose: to evaluate the protective effect of omega-3 long-chain unsaturated fatty acids on the progression of wet age-related macular degeneration (wAMD). Methods: this meta-analysis was designed, implemented, and analyzed in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocol and is reported following PRISMA guidelines. Results: in this study we included 5 observational trials, including 2 cross-sectional studies, 2 case-control studies, and 1 confrontation study. These tests are conducted in the U.S., Europe and Japan, and are of high quality. In general, people with high dietary long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) have a lower risk of progression to advanced age-related macular degeneration (AMD) (effect size, ES: 0.51, 95 % CI [0.34, 0.75], I2 = 70 %, p = 0.01). When assessing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake and wAMD risk a total of the three above studies were included, which also produced similar results. Conclusions: the highest DHA consumption reduced the risk of disease by 39 % (effect size: 0.61, 95 % CI [0.50, 0.74], I2 = 14 %, p = 0.31); compared with the lowest EPA consumption, the highest EPA consumption reduced the risk of wAMD by 32 % (ES: 0.68, 95 % CI [0.57, 0.82], I2 = 39 %, p = 0.20).

Introducción: Propósito: evaluar el efecto protector de los AGPICL omega-3 sobre la degeneración macular húmeda asociada a la edad (DMAE). Métodos: este metaanálisis fue diseñado, implementado y analizado de acuerdo con el protocolo de Metaanálisis de Estudios Observacionales en Epidemiología (MOOSE) y se informa siguiendo las directrices de PRISMA. Resultados: en este estudio se incluyeron 5 ensayos observacionales, entre ellos 2 estudios transversales, 2 estudios de casos y controles y 1 estudio de confrontación. Estos ensayos se realizan en Estados Unidos, Europa y Japón y son de alta calidad. En general, las personas con una dieta alta en ácidos grasos poliinsaturados de cadena larga (AGPICL omega-3) tienen un menor riesgo de progresión hacia la degeneración macular avanzada relacionada con la edad (DMAE) (tamaño del efecto, ES: 0,51, IC 95 % [0,34, 0,75], I2 = 70 %, p = 0,01). Al evaluar la ingesta de ácido docosahexaenoico (DHA) y ácido eicosapentaenoico (EPA) y el riesgo de DMAE se incluyeron en total tres de los estudios anteriores, que también arrojaron resultados similares. Conclusiones: el mayor consumo de DHA redujo el riesgo de enfermedad en un 39 % (tamaño del efecto: 0,61, IC del 95 % [0,50, 0,74], I2 = 14 %, p = 0,31); en comparación con el menor consumo de EPA, el mayor consumo de EPA redujo el riesgo de wAMD en un 32 % (ES: 0,68, IC del 95 % [0,57, 0,82], I2 = 39 %, p = 0,20).

ASSOCIATION OF PLASMA ω-3 FATTY ACIDS WITH EARLY AGE-RELATED MACULAR DEGENERATION IN THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS.

PURPOSE: To examine the association between omega-3 polyunsaturated fatty acids, docosahexaenoic acid, and eicosapentaenoic acid and age-related macular degeneration (AMD) in the Multi-Ethnic Study of Atherosclerosis cohort. METHODS: Multi-Ethnic Study of Atherosclerosis is a multicenter, prospective cohort study designed to identify risk factors for cardiovascular disease in four ethnic groups. Six thousand eight hundred and fourteen participants of White, African American, Hispanic/Latino, and Chinese descent, aged 45-84 years, were recruited, with those found to have cardiovascular disease excluded. Our study population included all Multi-Ethnic Study of Atherosclerosis participants with baseline polyunsaturated fatty acid measurements and retinal photography at Examination 5 (n = 3,772). Fundus photographs were assessed for AMD using a standard grading protocol. Relative risk regression (log link) determined associations between polyunsaturated fatty acid levels and AMD. RESULTS: There was a significant association between increasing docosahexaenoic acid levels and increasing docosahexaenoic acid + eicosapentaenoic acid levels with reduced risk for early AMD (n = 214 participants with early AMD, of which n = 99 (46.3%) are non-White). Eicosapentaenoic acid levels alone were not significantly associated with AMD. CONCLUSION: Our analysis suggests increasing levels of docosahexaenoic acid are associated with reduced risk for early AMD in a multiethnic cohort. This represents the first racially diverse study demonstrating an association between omega-3 polyunsaturated fatty acids and AMD risk.

Red blood cell fatty acids and age-related macular degeneration in postmenopausal women.

PURPOSE: To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women. METHODS: This analysis included 1456 postmenopausal women from the Women's Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5 years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake. RESULTS: No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish. CONCLUSIONS: RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk.

Global Burden of Dry Age-Related Macular Degeneration: A Targeted Literature Review.

PURPOSE: Age-related macular degeneration (AMD) is a leading cause of blindness, particularly in higher-income countries. Although dry AMD accounts for 85% to 90% of AMD cases, a comprehensive understanding of the global dry AMD burden is needed. METHODS: A targeted literature review was conducted in PubMed, MEDLINE, Embase, and the Cochrane Database of Systematic Reviews (1995-2019) to identify data on the epidemiology, management, and humanistic and economic burden of dry AMD in adults. A landscape analysis of patient-reported outcome (PRO) instruments in AMD was also conducted via searches in PubMed (1995-2019), ClinicalTrials.gov, PROQOLID, PROLABELS, and health technology assessment reports (2008-2018). FINDINGS: Thirty-seven of 4205 identified publications were included in the review. Dry AMD prevalence was 0.44% globally, varied across ethnic groups, and increased with age. Patients with dry AMD had higher risks of all-cause mortality (hazard ratio [HR] = 1.46; 95% CI, 0.99-2.16) and tobacco-related (HR = 2.86; 95% CI, 1.15-7.09) or cancer deaths (HR = 3.37; 95% CI, 1.56-7.29; P = 0.002) than those without dry AMD. Smoking, increasing age or cholesterol levels, and obesity are key risk factors for developing dry AMD. No treatment guidelines were identified for dry AMD specifically; management focuses on risk factor reduction and use of dietary supplements. In the United States and Italy, direct medical costs and health care resource utilization were lower in patients with dry versus wet AMD. Patients with dry AMD, particularly advanced disease, experienced significant visual function impairment. Dry AMD symptoms included reduced central vision, decreased ability to see at night, increased visual blurriness, distortion of straight lines and text, and faded color vision. Most PRO instruments used in AMD evaluations covered few, if any, of the identified symptoms reported by patients with dry AMD. Although the Quality of Life and Vision Function Questionnaire, 25-item National Eye Institute Vision Function Questionnaire, Low Vision Quality of Life, Impact of Vision Impairment-Very Low Vision, and Functional Reading Independence Index had strong content validity and psychometric properties in patients with dry AMD, they retained limited coverage of salient concepts. IMPLICATIONS: Despite dry AMD accounting for most AMD cases, there are substantial gaps in the published literature, particularly the humanistic and economic burden of disease and the lack of differentiation among dry, wet, or unspecified dry AMD. The significant burden of illness alludes to a high unmet need for tolerable and effective treatment options, as well as PRO instruments with more coverage of dry AMD symptoms and salient concepts.

Environmental and Nutritional Determinants of Macular Pigment in a Mexican Population.

Purpose: The carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin deposit at the macula as macular pigment (MP) and provide visual benefits and protection against macular diseases. The present study investigated MP, its nutritional and environmental determinants, and its constituent carotenoids in serum from a Mexican sample, in healthy participants and with metabolic diseases. Additionally, we compared these variables with an Irish sample. Methods: MP was measured in 215 subjects from a rural community in Mexico with dual-wavelength autofluorescence imaging reported as MP optical volume (MPOV). Dietary intake and serum concentrations of L and Z were evaluated. Results: The mean MPOV was 8429 (95% confidence interval, 8060-8797); range. 1171-15,976. The mean L and Z serum concentrations were 0.25 ± 0.15 µmol/L and 0.09 ± 0.04 µmol/L, respectively. The MPOV was positively correlated with L and Z serum concentrations (r = 0.347; P < 0.001 and r = 0.311; P < 0.001, respectively), but not with L + Z dietary estimates. Subjects with daily sunlight exposure of more than 50% were found to have significantly higher MPOV than those with less than 50% (P = 0.005). MPOV and serum concentrations of L and Z were significantly higher in the Mexican sample compared with the Irish sample, but this difference was not reflected in dietary analysis. Conclusions: These new data from a Mexican sample provide evidence of the multifactorial interactions and environmental determinants of MP such as sunlight exposure and dietary patterns. These findings will be essential for future studies in Mexico for eye health, visual function, and ocular pathology.

Dietary fatty acid intake, plasma fatty acid levels, and the risk of age-related macular degeneration (AMD): a dose-response meta-analysis of prospective cohort studies.

PURPOSE: Previous population studies on the associations between dietary fatty acids (FAs), plasma FAs levels, and the risk of age-related macular degeneration (AMD) have yielded inconclusive results. Herein, we conducted a dose-response meta-analysis to quantitatively evaluate the associations between specific type of dietary FAs, plasma FAs on early and advanced AMD risk. METHODS: PubMed, Web of Science, and EMBASE were systematically searched for observational cohort studies published through May 2020. For highest versus lowest comparison and dose-response analyses, the relative risk (RR) estimates with a 95% confidence interval (CI) were analyzed using random effects model. RESULTS: 11 studies with 167,581 participants were included in the meta-analysis. During the follow-up periods (ranging from 3 to 28 years), 6,318 cases of AMD were recorded. Dietary intake of docosahexaenoic acid (DHA) and eicosatetraenoic acid (EPA) combined (per 1 g/day increment) were found to be negatively associated with early AMD (RR: 0.67, 95% CI [0.51, 0.88]). Each 1 g/day increment of DHA (RR: 0.50, 95% CI [0.32, 0.78]) and EPA (RR: 0.40, 95% CI [0.18, 0.87]) was associated with a 50% and 60% reduction of early AMD risk, respectively. Plasma DHA (RR: 0.72, 95% CI [0.55, 0.95]) and EPA (RR: 0.57, 95% CI [0.40, 0.81]) indicated significant negative relationship with advanced AMD. CONCLUSION: Increasing dietary intake of ω-3 polyunsaturated fatty acids (PUFAs), specifically DHA and EPA, were associated with a reduced risk of early subtype of AMD, while other types of FAs did not present significant results. Further research is warranted to explore the potential association between dietary FA, plasma FA levels, and advanced subtype of AMD.

Religiousness, Anxiety and Depression in Patients with Glaucoma, Age-Related Macular Degeneration and Diabetic Retinopathy.

BACKGROUND: Many chronic medical conditions such as glaucoma, senile macular degeneration and diabetic retinopathy are further complicated by emotional and psychological disorders. Religiousness represents a part of a social culture and has a significant role in the prevention of mental difficulties of the patients, especially those belonging to older population. The aim of this study was to investigate the connection between religiousness, anxiety, and depression in patients with glaucoma, age-related macular degeneration and diabetic retinopathy and to test their connection related to different diagnosis. SUBJECTS AND METHODS: This cross-sectional study included 163 patients divided into three groups (glaucoma group, senile macular degeneration group and diabetic retinopathy group). Respondents voluntarily agreed to participate in the study and with assistance they fully completed the Scale of Religiousness, Hospital Anxiety and Depression Scale, General Health Questionnaire and demographic information (age, gender, education, employment and marital status). RESULTS: The results showed noticeable religiosity of the respondents (M=18.31, SD=5.28), but also the presence of anxiety (M=7.55, SD=3.73), especially in patients with glaucoma, as well as impaired mental health in AMD patients (M=19.56, SD=4.14). No differences were found in the severity of anxiety, depression, general health and religiosity between groups, but the presence of depression in subjects with age-related macular degeneration significantly affects the level of religiosity (p=0.032). CONCLUSION: These results unequivocally point to the need for further research and raising awareness of all health professionals about the importance of a holistic approach to the patient regardless of his diagnosis in order to identify the possible effective ways to deal with chronic disease considering all levels of patient's needs.

Foveal macular pigment dip in offspring of age-related macular degeneration patients is inversely associated with omega-3 index.

BACKGROUND: Offspring of parent(s) with age-related macular degeneration (AMD) have a 45% lifetime risk of developing the disease. High foveal macular pigment optical density (MPOD) is protective, whereas individuals with a "foveal macular pigment dip" (FMPD) are at increased risk. Shortage of the dietary carotenoids lutein, zeaxanthin as well as fish consumption are reported AMD risk factors. This Early Biomarkers of AMD (EBAMD) study evaluates serum factors that protect foveal MPOD architecture in Caucasian offspring of parent(s) with AMD. METHODS: N = 130 subjects [mean (SD) age 62.8 (8.6) years; 36/94 male/female] were recruited from Scripps Health/ Scripps Memorial Hospital/ Scripps Mericos Eye Institute between 2012 and 2017. Macula pigment 3D topography was evaluated using specular reflectance. Buccal genetic cheek swab, circulating serum dietary carotenoids and long-term RBC omega-3 fatty acid status, as well as common secondary clinical structural and vision function parameters were obtained. RESULTS: 41 % of offspring of AMD parent(s) presented with FMPD. These offspring were about 4 years younger than those without FMPD (controls; P = 0.012) and had thinner foveas (P = 0.010). There were no differences in gender, BMI, % body fat, visual acuity or contrast sensitivity between those with and without FMPD. % RBC membrane docosahexaenoic acid (DHA) was reduced in FMPD offspring vs. control offspring (P = 0.04). The Omega-3 Index was significantly decreased in the FMPD group (P = 0.03). CONCLUSIONS: The percentage of FMPD in AMD offspring is nearly twice that reported for the general population in the scientific literature. Offspring presenting FMPD had similar AMD genetic risk, but significantly reduced % RBC membrane omega-3 fatty acids and thinner foveas compared with those without FMPD. Our data supports the importance of 'essential fatty' acids as an independent AMD risk factor.

Effect of Vitamin D and ω-3 Fatty Acid Supplementation on Risk of Age-Related Macular Degeneration: An Ancillary Study of the VITAL Randomized Clinical Trial.

Importance: Observational studies suggest that higher intake or blood levels of vitamin D and marine ω-3 fatty acids may be associated with lower risks of age-related macular degeneration (AMD). However, evidence from randomized trials is limited. Objective: To evaluate whether daily supplementation with vitamin D3, marine ω-3 fatty acids, or both prevents the development or progression of AMD. Design, Setting, and Participants: This was a prespecified ancillary study of the Vitamin D and Omega-3 Trial (VITAL), a nationwide, placebo-controlled, 2 × 2 factorial design randomized clinical trial of supplementation with vitamin D and marine ω-3 fatty acids for the primary prevention of cancer and cardiovascular disease. Participants included 25 871 men and women in the US. Randomization was from November 2011 to March 2014, and study pill-taking ended as planned on December 31, 2017. Interventions: Vitamin D3 (cholecalciferol), 2000 IU per day, and marine ω-3 fatty acids, 1 g per day. Main Outcomes and Measures: The primary end point was total AMD events, a composite of incident cases of AMD plus cases of progression to advanced AMD among participants with AMD at baseline, based on self-report confirmed by medical record review. Analyses were conducted using the intention-to-treat population. Results: In total, 25 871 participants with a mean (SD) age of 67.1 (7.0) years were included in the trial. Of them, 50.6% were women, 71.3% were self-declared non-Hispanic White participants, and 20.2% were Black participants. During a median (range) of 5.3 (3.8-6.1) years of treatment and follow-up, 324 participants experienced an AMD event (285 incident AMD and 39 progression to advanced AMD). For vitamin D3, there were 163 events in the treated group and 161 in the placebo group (hazard ratio [HR], 1.02; 95% CI, 0.82-1.27). For ω-3 fatty acids, there were 157 events in the treated group and 167 in the placebo group (HR, 0.94; 95% CI, 0.76-1.17). In analyses of individual components for the primary end point, HRs comparing vitamin D3 groups were 1.09 (95% CI, 0.86-1.37) for incident AMD and 0.63 (95% CI, 0.33-1.21) for AMD progression. For ω-3 fatty acids, HRs were 0.93 (95% CI, 0.73-1.17) for incident AMD and 1.05 (95% CI, 0.56-1.97) for AMD progression. Conclusion and Relevance: Neither vitamin D3 nor marine ω-3 fatty acid supplementation had a significant overall effect on AMD incidence or progression. Trial Registration: ClinicalTrials.gov Identifier: NCT01782352.

RISK OF AGE-RELATED MACULAR DEGENERATION IN PATIENTS WITH PERIODONTITIS: A Nationwide Population-Based Cohort Study.

PURPOSE: Periodontitis is an inflammatory disease that results in loss of connective tissue and bone support. Evidence shows a possible relationship between periodontitis and age-related macular degeneration (AMD). METHODS: This population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan, with a 13-year follow-up, to investigate the risk of AMD in patients with periodontitis. The periodontitis cohort included patients with newly diagnosed periodontitis between 2000 and 2012. The nonperiodontitis cohort was frequency-matched with the periodontitis cohort by age and sex, with a sample size of 41,661 in each cohort. RESULTS: Patients with periodontitis had an increased risk of developing AMD compared with individuals without periodontitis (5.95 vs. 3.41 per 1,000 person-years, adjusted hazard ratio = 1.58 [95% confidence interval, 1.46-1.70]). The risk of developing AMD remained significant after stratification by age (adjusted hazard ratio = 1.48 [1.34-1.64] for age <65 years and 1.76 [1.57-1.97] for age ≥65 years), sex (adjusted hazard ratio = 1.40 [1.26-1.55] for women and 1.82 [1.63-2.04] for men), and presence of comorbidity (adjusted hazard ratio = 1.52 [1.40-1.66] for with comorbidity and 1.92 [1.63-2.26] for without comorbidity). In addition, patients with periodontitis showed an increased incidence for both nonexudative type AMD (5.43 vs. 3.13 per 1,000 person-years) and exudative type AMD (0.52 vs. 0.28 per 1,000 person-years). CONCLUSION: People with periodontitis could be at a greater risk of developing AMD than those without periodontitis. However, we need more evidence to support this association.

Geographic Atrophy and micronutritional supplements: A complex relationship.

In 2019, the Age-Related Eye Disease Study (AREDS) remains the basis for micronutritional supplement guidelines aiming to slow the progression of Age-Related Macular Degeneration (AMD) and reduce the risk of neovascularization. However, for Geographic Atrophy (GA) patients specifically, there seem to be more arguments for prescribing micronutritional supplements for the prevention of neovascular complications than to slow the progression of the atrophy. The AREDS report 8 showed a significant decrease in AMD progression over a five-year follow-up associated with a formulation containing antioxidants and zinc. It is noteworthy that the protective effect that was demonstrated was mainly related to the risk of a neovascularization and that the AREDS did not really demonstrate a protective effect that would slow the progression of GA. The 2013 AREDS II results have led to a change in the AREDS formulation. Nevertheless, the replacement of beta-carotene by lutein and zeaxanthine and the addition of Omega-3 did not add any further evidence for a protective effect on GA. Furthermore, the AREDS study used color photographs rather than fundus autofluorescence or OCT to assess the presence or the evolution of patches of atrophy. Over the last 10 years, it has been shown that OCT is far more accurate than color photographs to measure the size of the atrophic areas and to evaluate the extent of alterations in the chorioretinal layers. While lack of evidence of a protective effect of the AREDS formulation for GA is not a proof of the absence of effect, many publications seem to have taken the results of the AREDS in such a global way that the lack of evidence concerning GA seems to have been ignored. Micronutrition supplements are well prescribed for AMD patients, and the key factor for adherence is explanation to the patient. So far, it appears worth explaining to GA patients that prescription of the AREDS formulation is mainly aimed at reducing the risk of neovascularization.

Review of neovascular age-related macular degeneration treatment options.

Due to an aging population, visual impairment from neovascular age-related macular degeneration (nAMD) is increasing in the United States. Despite unprecedented improvements in vision preservation that patients can achieve with anti-vascular endothelial growth factor (VEGF) agents, innovations are needed to reduce the burden of intravitreal injections and improve outcomes in patients who do not respond adequately to currently available agents. The best present option for vision preservation is a "zero-tolerance for fluid" schedule of monitoring and intravitreal injections that patients may need to follow for many years. This treatment burden has resulted in patients not achieving optimal benefit or even falling through the cracks. This article reviews state-of-the-art management approaches including as-needed and treat-and-extend dosing regimens designed to reduce treatment burden.