Prevalence and risk factors for impaired activities of daily living in patients with neo-vascular age-related macular degeneration who present for anti-VEGF treatment.

BACKGROUND/OBJECTIVES: To assess the prevalence and correlates of impaired activities of daily living (ADLs) in patients with neovascular age-related macular degeneration (nAMD) who present for anti-vascular endothelial growth factor (VEGF) therapy. METHODS: In a clinic-based cohort of 437 patients with nAMD who presented for anti-VEGF therapy, the Older American Resources and Services Scale (OARS) was administered to assess for impairments in basic, instrumental and total ADL. Logistic regression analyses were conducted to determine odds ratios (OR) and 95% confidence intervals (CI) for factors associated with ADL impairment. RESULTS: The prevalence of impaired basic, instrumental and total ADL was 37.76%, 67.82% and 39.59%, respectively. In multivariate-adjusted models, moderate visual impairment [OR 5.65, 95% CI (2.31-13.83) and blindness [OR 5.43, 95% CI (2.09-14.12)] were associated with greater odds of impaired total ADL. Depressive symptoms [OR 2.08, 95% CI (1.08-4.00)], the presence of any disability [OR 3.16, 95% CI (1.64-0.07)] and never driving [OR 4.00, 95% CI (1.60-10.00)] were also positively associated with total ADL impairment. Better vision-related quality of life (QoL) was inversely associated with impaired instrumental ADL whilst higher health-related QoL scores were associated with decreased odds of total ADL impairment. CONCLUSIONS: There is a high prevalence rate of ADL impairment among nAMD patients presenting for therapy. Visual impairment, never driving, poor physical and mental health increased the odds of experiencing ADL impairment whilst better VRQoL and HRQoL reduced the odds of impairment.

Associations between intake of dietary flavonoids and the 10-year incidence of tinnitus in older adults.

PURPOSE: Dietary flavonoids are bioactive compounds that have been widely investigated for their associations with vascular health outcomes. As the development of tinnitus has been linked to vascular pathways, dietary flavonoids may have role in the prevention of tinnitus symptoms. This study reports the associations between the intakes of major classes of dietary flavonoids and 10-year incidence of tinnitus. METHODS: Of the 1753 participants (aged ≥ 50 years) from the Blue Mountains Hearing Study with complete baseline data on tinnitus symptoms and dietary intakes, 536 (31%) cases of tinnitus were identified and excluded from further analysis. Dietary data was collected using a semi-quantitative food frequency questionnaire and intakes of the five major classes of flavonoids were determined using U.S. Department of Agriculture flavonoid databases. Presence of prolonged tinnitus was assessed by a positive response to a single question administered by an audiologist. RESULTS: Of the remaining 1217 participants without tinnitus at baseline, 222 (18%) incident cases of tinnitus were identified over 10 years. After age-sex adjustment, participants in the third versus first quartile of proanthocyanidin intake were significantly less likely to develop incident tinnitus by 36% (HR = 0.64; 95% CI 0.43-0.96, Ptrend = 0.04). Following multivariable adjustment, this protective trend was non-significant (HR = 0.60; 95% CI 0.39-0.92; Ptrend = 0.06). Similarly, a non-significant protective trend was observed when comparing the fourth versus first quartile of intake of all flavonoids (OR = 0.61; 95% CI 0.39-0.96). No other associations were observed. CONCLUSION: Our findings do not support the hypothesis that dietary flavonoids are protective against the development of tinnitus over 10 years. The weak significant association observed between proanthocyanidin and incident tinnitus may be a chance finding as there was no significant trend following multivariate adjustments and, therefore, requires further studies to investigate these associations.

Evaluation of educational interventions on eye health for dietetic and pharmacy professions: a pre-post study.

BACKGROUND: We piloted an educational intervention that aimed to enhance awareness about nutrition-age-related macular degeneration (AMD) links among practising and student dietitians then expanded the scope of this intervention to include general eye health, which was delivered to pharmacy students. METHODS: A pilot intervention was conducted in 2019 at the Dietitians Australia Conference (Gold Coast, Australia) where practising and student dietitians underwent a 2-hour small group educational workshop on nutrition and AMD links. Pre-post questionnaires were administered to participants, with voluntary completion of both questionnaires an indicator of consent to participate in the intervention. The primary intervention outcome was a change in AMD-related nutrition knowledge pre-post intervention. A larger intervention was then conducted at the University of Sydney (Sydney, Australia) where pharmacy students underwent a 4-hour educational module to improve general eye health knowledge, as well as student perceptions and attitudes towards a pharmacists' role in low vision care. Similarly, pre-post questionnaires were administered, with voluntary completion of both questionnaires an indicator of consent to participate in the intervention. The primary intervention outcomes were changes in total knowledge, total perception and total attitude scores pre-post intervention. RESULTS: (1) Among 10 accredited and 5 student dietitians, there was significant overall knowledge improvement (mean pre-post score: 7.07 ± 1.94 vs. 10.8 ± 1.01, p = 0.001) specifically around appropriate dietary advice, food sources of key AMD-related nutrients, and awareness of supplements. (2) Among 179 second-year pharmacy students enrolled in the 'Pharmacy Practice' Unit of Study (Bachelor of Pharmacy, University of Sydney), total eye health knowledge (6.25 ± 1.93 vs. 6.64 ± 2.0; p = 0.011) significantly improved, along with total perception scores (41.54 ± 5.26 vs. 42.45 ± 4.95; p = 0.004). Total attitude scores were not significantly different. CONCLUSIONS: The pilot intervention improved relevant nutrition-AMD knowledge among practising/student dietitians. The modified intervention for pharmacy students also significantly improved general eye health knowledge as well as students' perception of a pharmacists' role in low vision care.

Dietary flavonoids are associated with longitudinal treatment outcomes in neovascular age-related macular degeneration.

PURPOSE: To assess whether dietary intake of flavonoids are associated with longitudinal treatment outcomes of patients with neovascular age-related macular degeneration (nAMD). METHODS: 547 participants with nAMD were recruited at baseline, 494 were followed-up after receiving 12 months of anti-vascular endothelial growth factor (anti-VEGF) therapy. Baseline dietary intake of flavonoids was determined using a validated food frequency questionnaire. At follow-up, presence of intra-retinal and sub-retinal fluid (IRF and SRF), retinal pigment epithelium detachment and measurements of central macular thickness (CMT) were recorded from optical coherence tomography scans. Visual acuity (VA) was documented using LogMAR charts. RESULTS: Participants in the first tertile of intake of the flavonol quercetin, and the flavan-3-ols epigallocatechin-3-gallate and epigallocatechin had significantly worse vision than participants in the third tertile-multivariable-adjusted least square (LS) mean VA: 14.68 vs. 19.53 (p = 0.04); 14.06 vs. 18.89 (p = 0.04); 13.86 vs. 18.86 (p = 0.03), respectively. Participants in the first compared to the third tertile of flavan-3-ol, epigallocatechin-3-gallate and epigallocatechin intake all had a twofold higher risk of IRF, multivariable-adjusted p trend of: 0.03, 0.01 and 0.02, respectively. The first vs. the third tertile of tea intake had significantly worse vision (LS mean VA: 13.49 vs. 19.04, p = 0.02), increased risk of IRF (OR 2.13, 95% CI 1.18-3.85) and greater mean CMT (279.59 µm vs. 256.52 µm, p = 0.04). CONCLUSIONS: Higher intakes of dietary flavonoids, specifically flavonols and flavan-3-ols, could be associated with better long-term treatment outcomes in nAMD patients receiving anti-VEGF therapy. Confirmation of these associations in interventional studies could result in promising new therapeutic approaches to the treatment of nAMD.

Retinal Vasculature Fractal and Stroke Mortality.

BACKGROUND AND PURPOSE: Fractal analysis is a method of quantifying the branching complexity and density of the retinal vessels. We hypothesized that reduced fractal dimension, signifying a sparser vascular network, is associated with long-term stroke mortality. METHODS: We examined the relationship of fractal dimension and stroke mortality in a prospective, population-based cohort of 3143 participants aged 49 years or older. Fractal dimension was measured from digitized fundus photographs using a computer-automated method. Stroke mortality was documented from Australian National Death Index records. We defined reduced fractal dimension as values in the lowest quartile. RESULTS: Over 12 years, there were 132 (4.2%) stroke-related deaths. Stroke-related mortality was higher in participants with reduced fractal dimension (lowest quartile) compared with the highest quartile (7.7% versus 1.3%, P<0.01). After controlling for age, gender, smoking, blood pressure, history of stroke, and other factors, participants with reduced fractal dimension had higher stroke mortality (hazard ratio, 2.42 [95% CI, 1.15-5.07], lowest versus highest quartile). When modeled as a continuous variable, reduced fractal dimension was associated with increased stroke mortality (multivariable-adjusted hazard ratio, 1.26 [95% CI, 1.06-1.51], per SD decrease). CONCLUSIONS: Reduced retinal vascular fractal dimension is independently associated with 12-year stroke mortality. Reduced fractal dimension may indicate cerebral tissue hypoxia and increased risk of stroke.

Association between vision and hearing impairment and successful aging over five years.

OBJECTIVE: We aimed to prospectively examine the relationship between vision and hearing loss and successful aging in a cohort of older adults. STUDY DESIGN: We analyzed 5-year data (1997-9 to 2002-4) from 1,085 adults aged 55+ years, who were free of cancer, coronary artery disease and stroke at baseline and who had complete data on sensory loss. MAIN OUTCOME MEASURES: Visual impairment was defined as visual acuity <20/40 (better eye), and hearing impairment as average pure-tone air conduction threshold >25 dBHL (500-4000 Hz, better ear). Successful aging was defined as the absence of: disability, depressive symptoms, cognitive impairment, respiratory symptoms and chronic diseases (cancer, coronary artery disease and stroke) at 5-year follow-up. RESULTS: At 5-year follow-up, 243 (22.4%) participants had died and 248 (22.9%) had aged successfully. After multivariable adjustment, participants who had either best-corrected visual impairment or bilateral hearing impairment, versus those who did not have sensory impairment at baseline, had 37% reduced odds of successful aging after 5 years: OR 0.63 (95% CI 0.43-0.94). Concurrent vision and hearing loss at baseline was not associated with 5-year aging status. Participants with moderate and severe hearing handicap at baseline had 50% and 61% reduced odds of aging successfully after 5 years, respectively. CONCLUSION: The presence of a single sensory impairment in older adults was associated with reduced odds of being disease-free and fully functional or having aged successfully, 5 years later. Objectively measured hearing loss and self-perceived hearing handicap, rather than vision loss, was more likely to negatively influence 5-year aging status.

Prevalence and risk factors for depressive symptoms in patients with neovascular age-related macular degeneration who present for anti-VEGF therapy.

PURPOSE: To examine the prevalence and risk factors for depressive symptoms in patients with neovascular age-related macular degeneration (nAMD) presenting for anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: In a clinic-based cohort of 547 patients with nAMD who presented for treatment, the Centre of Epidemiological Studies Depression 10-point scale (CES-D-10) and Mental Health Index (MHI) component of the 36-item Short Form Survey were administered to assess for the presence of depressive symptoms. Logistic regression analyses were used to calculate odds ratios and 95% confidence intervals for factors associated with an increased likelihood of depressive symptoms. RESULTS: The prevalence of depressive symptoms was 42.04% and 31.78% as per the CES-D-10 and MHI scales, respectively. Poor self-rated health (SRH) is associated with increased odds of depressive symptoms [multivariable-adjusted OR: 3.00 (95% CI 1.90-4.73) for CES-D-10; OR: 2.67 (95% CI 1.67-4.28) for MHI]. Impaired activities of daily living (ADLs) [multivariable-adjusted OR: 2.62 (95% CI 1.56-4.38) for CES-D-10; OR: 3.59 (95% CI 2.10-6.15) for MHI] and a visual function score within the two lowest quartiles were also associated with increased odds of depressive symptoms using both scales. CONCLUSION: A high prevalence of depressive symptoms was observed among nAMD patients presenting for treatment. Poorer SRH, ADL impairment and reduced visual function were associated with increased odds of depressive symptoms.

Dietary antioxidants are associated with presence of intra- and sub-retinal fluid in neovascular age-related macular degeneration after 1 year.

PURPOSE: To assess whether dietary intake of antioxidants, fruits, vegetables and fish is associated with 12-month treatment outcomes in neovascular age-related macular degeneration (nAMD) patients. METHODS: A total of 547 participants were diagnosed with nAMD at baseline, of whom 494 were followed up after 12 months of antivascular endothelial growth factor therapy. Dietary intakes were determined using a validated food frequency questionnaire. Presence of intra-retinal and sub-retinal fluid (IRF, SRF), pigment epithelial detachment (PED) and central macular thickness (CMT) were recorded from optical coherence tomography images. Best-corrected visual acuity was recorded using log of the Minimum Angle of Resolution (LogMAR) charts. RESULTS: Participants in the upper three quartiles combined compared to those in the first quartile of baseline dietary zinc intake had 49% reduced odds of SRF 12 months later, multivariable-adjusted odds ratio (OR) 0.51 [95% confidence interval (CI) 0.30-0.89]. The upper three quartiles combined compared to the first quartile of ß-carotene intake had 90% greater odds of IRF presence at 12-month follow-up, multivariable-adjusted OR 1.90 (95% CI 1.04-3.46). The highest versus lowest quartile of dietary ß-carotene intake had a nearly twofold greater odds of PED presence, multivariable-adjusted OR 1.99 (95% CI 1.03-3.84). CONCLUSION: A higher intake of dietary zinc was associated with a reduced likelihood of SRF at 1 year. Conversely, a higher intake of dietary ß-carotene was associated with an increased risk of IRF and PED. These findings underscore the importance of ongoing nutritional advice for nAMD patients presenting for treatment.

Smoking and treatment outcomes of neovascular age-related macular degeneration over 12 months.

BACKGROUND: To assess the association of smoking with age of onset of neovascular age-related macular degeneration (nAMD), visual acuity (VA), central macular thickness (CMT) and the presence of fluid in patients with nAMD. METHODS: 547 patients with nAMD were recruited from a tertiary eye clinic during 2012-2015; of these, 490 patients were followed up 12 months later. Clinical diagnosis of nAMD was confirmed by a retinal specialist. Smoking was determined from self-reported history as never, past or current. Age of onset was defined as date of first recorded diagnosis of nAMD in either eye or date of first anti-vascular endothelial growth factor injection. CMT and presence of fluid were recorded from spectral-domain optical coherence tomography images. VA was recorded as number of letters read at 3 m. RESULTS: After multivariable adjustment, current smokers developed nAMD at an average 5.5 years younger age than never smokers and 4.4 years younger age than past smokers (p<0.0001 and p=0.0008, respectively). At baseline, adjusted mean CMT was significantly higher in current compared with past smokers (259.2 µm vs 231.9 µm, respectively, p=0.04). Current smokers versus never smokers had greater odds of presence of subretinal fluid at 12-month follow-up: multivariable-adjusted OR 1.99 (95% CI 1.09 to 3.67). Smoking status was not significantly associated with VA over 12 months. CONCLUSIONS: Current smoking was associated with a younger age of nAMD onset and key treatment outcomes such as higher mean CMT and greater odds of subretinal fluid presence. These findings suggest that smoking cessation may benefit patients being treated for nAMD.

Evaluation of a Novel Tool for Screening Inadequate Food Intake in Age-Related Macular Degeneration Patients.

Diet assessment tools provide valuable nutrition information in research and clinical settings. With growing evidence supporting dietary modification to delay development and progression of age-related macular degeneration (AMD), an AMD-specific diet assessment tool could encourage eye-care practitioners to refer patients in need of further dietary behavioural support to a dietitian and/or support network. Therefore, the aim of this study was to evaluate clinical use of a novel, short dietary questionnaire (SDQ-AMD) to screen for inadequate food intake in AMD patients by comparing it against a validated food frequency questionnaire (FFQ). Recruitment sources included Sydney-based private eye clinics and research databases (N = 155; 57% female; 78 ± 8 years). Scoring criteria based on the Australian Dietary Guidelines and dietary recommendations for AMD in literature were developed and applied to dietary data from the FFQ and SDQ-AMD. Bland-Altman plot of difference suggests agreement between the FFQ and SDQ-AMD as most mean difference scores were within the 95% CI (6.91, -9.94), and no significant bias between the scores as the mean score increased ((regression equation: y = 0.11x - 2.60) (95% CI: -0.058, 0.275, p-value = 0.20)). Scores were also significantly correlated (0.57, p ≤ 0.0001). The SDQ-AMD shows potential as a diet screening tool for clinical use, however, additional studies are warranted to validate the SDQ-AMD.

Retinal microvascular changes in microvascular angina: Findings from the Australian Heart Eye Study.

OBJECTIVE: Microvascular changes in microvascular angina are poorly understood due to difficulties in imaging the coronary microcirculation in vivo. The retinal microvasculature may reflect changes in coronary microcirculation. We assessed microvascular changes in the retina in patients with microvascular angina and compared them with patients with angiographically proven coronary artery disease. METHODS: We performed retinal photography and coronary angiography on 915 patients. Retinal vessel calibers were measured using a validated computer-assisted method; coronary artery disease was graded from coronary angiograms. Microvascular angina was defined as angina with <25% stenosis in all coronary epicardial arteries. RESULTS: A total of 139 patients (15.2%) had microvascular angina, while 776 (84.8%) had coronary artery disease. Participants with microvascular angina and coronary artery disease had similar retinal arteriolar and venular calibers. After adjustment for age, ethnicity, mean arterial pressure, diabetes, current smoking, body mass index, and fellow vessel caliber, women with smaller venules were threefold more likely to have microvascular angina than women with larger venules (multivariable-adjusted odds ratio 3.54, 95% confidence interval 1.35 to 9.24, P < 0.01). This difference was not observed in men. CONCLUSIONS: Microvascular angina in women was associated with microvascular changes distinct from those in coronary artery disease.

Association between head injury and concussion with retinal vessel caliber.

The adverse long-term consequences following traumatic brain injury are poorly understood, particularly on the cerebral microvasculature. Retinal vessels are a surrogate marker of cerebral vascular changes. We therefore aimed to examine the cross-sectional association between serious head injury or being knocked unconscious, and/or concussion and retinal microvascular signs, specifically, mean retinal arteriolar and venular calibre, in older adults after accounting for potential confounders. This cohort study involved 2,624 adults with mean age of 66.9 (±9.1) years who self-reported head injury and concussion parameters, and had gradable retinal photographs. Face-to-face interviews with trained interviewers allowed participants to report prior serious head injury or being knocked unconscious, and/or a previous diagnosis of concussion by a medical professional. Fundus photographs were taken and retinal vascular calibre measured using computer-assisted techniques and summarized. There were 25.9%, 15.3% and 10.1% who reported a prior serious head injury or being "knocked unconscious", concussion, and both, respectively. Participants in the first group compared to non-injured participants had significantly wider (~2 µm) mean retinal venular calibre (p = 0.02), after adjusting for age, sex, smoking, body mass index, mean arterial blood pressure, type 2 diabetes and fellow vessel calibre. No significant associations were observed in people reporting medically diagnosed concussion or with mean retinal arteriolar calibre. Our exploratory study suggests that head injury is independently associated with wider retinal venular caliber. These findings warrant further investigation in longitudinal cohort studies.

Combined influence of poor health behaviours on the prevalence and 15-year incidence of age-related macular degeneration.

We aimed to establish the collective influence of four lifestyle practices (physical activity, diet, smoking and alcohol consumption) on the prevalence and incidence of AMD. At baseline, 2428 participants aged 49+ with complete lifestyle and AMD data were examined, and of these, 1903 participants were re-examined 15 years later. AMD was assessed from retinal photographs. A health behaviour score was calculated, allocating 1 point for each poor behaviour: current smoking; fruits and vegetables consumed <4 serves daily; <3 episodes of physical activity per week; and >2 alcoholic drinks per day. Cross-sectional analysis showed that participants who engaged in all 4 poor health behaviours (n = 29) versus those who did not engage in unhealthy behaviours (reference group; n = 677) had greater odds of any and late AMD: multivariable-adjusted OR, 5.14 (95% CI, 1.04-25.45) and OR 29.53 (95% CI 2.72-321.16), respectively. A marginally non-significant association was observed between increasing number of poor health behaviours and 15-year incidence of early AMD (multivariable-adjusted P-trend = 0.08). Our data suggests that motivating patients with AMD to eat better, exercise more, limit alcohol intake and avoid smoking seems advisable to decelerate the development or worsening of existing AMD.

Metabolic syndrome and retinal microvascular calibre in a high cardiovascular disease risk cohort.

AIMS: To investigate the independent associations between metabolic syndrome and retinal vessel calibre in a high cardiovascular risk cohort, and to determine whether these associations also exist in patients without diabetes, hypertension or coronary artery disease (CAD). METHODS: The Australian Heart Eye Study is an observational study that surveyed 1680 participants who presented to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. Metabolic syndrome was defined according to the Third Report of the National Cholesterol Education Program. Retinal arteriolar calibre narrowing and retinal venular calibre widening were measured from retinal photographs. CAD was quantified using severity (Gensini) and extent scores. Diabetes and hypertension were defined from clinical investigation (fasting plasma glucose >7.0 mmol/L and blood pressure >130/85 mm Hg) or from self-reported clinical diagnosis, including the use of medications. RESULTS: A total of 979 participants had complete information on metabolic syndrome components and were included in cross-sectional analyses. After adjusting for age, sex, smoking status and fellow vessel calibre, persons with metabolic syndrome (compared with persons without metabolic syndrome) had narrower retinal arteriolar calibre (mean difference 4.3 µm, p<0.0001). No significant difference in venular calibre was observed (p=0.05). This association persisted in persons without diabetes (mean arteriolar calibre difference 4.4 µm, p=0.0006) but not in participants without CAD and those without hypertension. CONCLUSIONS: Metabolic syndrome is independently associated with narrower retinal arterioles but not wider retinal venules among those at high risk of CAD. The association between metabolic syndrome and narrower retinal arterioles is likely due to the presence of CAD or hypertension in individuals with this syndrome, as the association is not significant in individuals without hypertension or without CAD.

Association between Retinal Arteriolar and Venule Calibre with Prevalent Heart Failure: A Cross-Sectional Study.

BACKGROUND: There is evidence to suggest that microvascular disease, particularly diabetic retinopathy, plays a role in the pathogenesis of HF. However, whether changes in retinal vessel calibre predicts HF is unclear. The purpose of this study was to examine the association of retinal microvascular structure with prevalent heart failure (HF). METHODS: The Australian Heart Eye Study (AHES) is a cross-sectional study that surveyed 1680 participants who presented to a tertiary referral hospital for the evaluation of potential coronary artery disease by coronary angiography. Retinal vessel calibre was graded using retinal photography and participants' self-reported echocardiography-confirmed HF was obtained via an extensive medical questionnaire. RESULTS: There were 107 participants (8.1%) with prevalent self-reported HF. Persons with wider retinal arteriolar calibre (comparing highest versus lowest tertile or reference) were more likely to have prevalent HF (OR 3.5; 95% CI, 1.7-7.2) when adjusted for age and sex. After further adjustment for body mass index, hypertension, diabetes, smoking status, triglycerides and estimated glomerular filtration rate, this association remained significant (OR 4.5; 95% CI, 2.0-9.8). After further stratification, this association remained significant among participants with diabetes (OR 10.3; 95% CI, 2.7-39.3) but not in those without diabetes (OR 2.7; 95% CI, 0.9-7.5). The strength of this association was not dependent on the length of history of diabetes, or retinopathy status. There was no significant association between retinal venular calibre and prevalence of HF. CONCLUSIONS: Wider retinal arteriolar diameter was significantly and independently associated with prevalent HF in participants of a cross-sectional study. This association was significant stronger among participants with diabetes compared to without diabetes. No association was found between retinal venule calibre with prevalent HF.

The Incidence and Progression of Age-Related Macular Degeneration over 15 Years: The Blue Mountains Eye Study.

PURPOSE: To assess the 15-year incidence and progression of age-related macular degeneration (AMD) in an older Australian population. DESIGN: Population-based cohort study. PARTICIPANTS: Blue Mountains Eye Study (BMES) participants (n = 3654) aged 49+ years were examined during 1992-1994. Of these, 2334 (75.8% of survivors) were reexamined after 5 years (1997-1999), 1952 (76.7% of survivors) after 10 years (2002-2004), and 1149 (56.1% of survivors) after 15 years (2007-2010). METHODS: Color retinal photographs were taken, and comprehensive questionnaires were administered at each visit and DNA was genotyped. Retinal photographic grading was performed by the same graders following the Wisconsin AMD grading protocol. Side-by-side comparisons were used to confirm newly developed AMD lesions. Incidence was estimated using Kaplan-Meier estimates. Associations of AMD incidence with age, sex, smoking status, presence of the complement factor H (CFH)-rs1061170 and age-related maculopathy susceptibility 2 (ARMS2)-rs10490924 polymorphisms, and fish consumption were analyzed using discrete logistic regression models. Generalized estimation equation models were used to assess the risk of incident late AMD associated with baseline AMD lesion characteristics. MAIN OUTCOME MEASURES: The 15-year incidence and progression of AMD, and associated factors. RESULTS: The 15-year incidence was 22.7% for early AMD and 6.8% for late AMD. After adjusting for competing risks, early and late AMD incidence were 15.1% and 4.1%, respectively. Age was strongly associated with early and late AMD incidence (both P < 0.0001). After age standardization to the Beaver Dam Eye Study (BDES) population, early and late AMD incidence in the BMES were 13.1% and 3.3%, respectively. Female sex and the presence of both risk alleles of CFH-rs1061170 or ARMS2-rs10490924 were independently associated with early AMD incidence, whereas current smoking and presence of ≥1 risk allele of CFH-rs1061170 or ARMS2-rs10490924 were associated with late AMD incidence. Fish consumption was inversely associated with late but not early AMD incidence. Severity of early AMD lesion characteristics was a strong predictor of progression to late AMD. CONCLUSIONS: We documented the 15-year incidence of early and late AMD in an older Australian population that were comparable to BDES observations. Risk of progression to late AMD was strongly associated with severity of early AMD lesions.

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

Physical activity and the 15-year incidence of age-related macular degeneration.

PURPOSE: There is uncertainty in the published literature as to whether physical activity should be advocated for age-related macular degeneration (AMD) prevention. We aimed to assess prospectively the association between physical activity and the 15-year incidence of AMD in older adults. METHODS: We assessed AMD from retinal photographs. Participants provided details of walking exercise and the performance of moderate or vigorous activities, which were used to calculate metabolic equivalents (METs). RESULTS: After adjusting for age, adults aged ≥ 75 years in the highest tertile (the most physically active) compared to those in the lowest tertile (least physically active) were 79% less likely to have incident late AMD over the 15 years (odds ratio [OR], 0.21; 95% confidence intervals [CI], 0.05-0.95). However, after further adjusting for sex, body mass index, smoking, fish consumption, and white cell count, this association was no longer statistically significant (OR, 0.26; 95% CI, 0.06-1.28). Significant associations were not found in those aged <75 or with the 15-year cumulative incidence of early AMD. CONCLUSIONS: Physical activity did not influence the risk of AMD over 15 years in older adults, independent of diet, smoking, white cell count, and body mass index.