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Current prediction models for advanced age-related macular degeneration (AMD) are based on a restrictive set of risk factors. The objective of this study was to develop a comprehensive prediction model applying a machine learning algorithm allowing selection of the most predictive risk factors automatically. Two population-based cohort studies. The Rotterdam Study I (RS-I; training set) included 3838 participants 55 years of age or older, with a median follow-up period of 10.8 years, and 108 incident cases of advanced AMD. The Antioxydants, Lipids Essentiels, Nutrition et Maladies Oculaires (ALIENOR) study (test set) included 362 participants 73 years of age or older, with a median follow-up period of 6.5 years, and 33 incident cases of advanced AMD. The prediction model used the bootstrap least absolute shrinkage and selection operator (LASSO) method for survival analysis to select the best predictors of incident advanced AMD in the training set. Predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). Incident advanced AMD (atrophic, neovascular, or both), based on standardized interpretation of retinal photographs. The prediction model retained (1) age, (2) a combination of phenotypic predictors (based on the presence of intermediate drusen, hyperpigmentation in one or both eyes, and Age-Related Eye Disease Study simplified score), (3) a summary genetic risk score based on 49 single nucleotide polymorphisms, (4) smoking, (5) diet quality, (6) education, and (7) pulse pressure. The cross-validated AUC estimation in RS-I was 0.92 (95% confidence interval [CI], 0.88–0.97) at 5 years, 0.92 (95% CI, 0.90–0.95) at 10 years, and 0.91 (95% CI, 0.88–0.94) at 15 years. In ALIENOR, the AUC reached 0.92 at 5 years (95% CI, 0.87–0.98). In terms of calibration, the model tended to underestimate the cumulative incidence of advanced AMD for the high-risk groups, especially in ALIENOR. This prediction model reached high discrimination abilities, paving the way toward making precision medicine for AMD patients a reality in the near future. [ABSTRACT FROM AUTHOR]

Purpose: To describe the use of eye care services among adults treated for diabetes from 2008 to 2017 in the French population. Methods: We used a random representative sampling of the French national health insurance database. Participants were adults treated for diabetes. Data regarding visits to ophthalmologists, eye examination procedures, and medical treatments were extracted using reimbursement codes. Cross-sectional analyses of eye care claims were performed each year from 2008 to 2017. Results: Less than 50% of people with diabetes underwent an annual eye examination (2008: 44.7%; 2017: 47.9%), and less than two-thirds underwent a biennial eye examination (2008-2009: 62.6%; 2016-2017: 66.4%). From 2008 to 2017, the yearly use of optical coherence tomography examinations increased steadily and markedly from 2.7% to 16.2%, while the use of fluorescein and indocyanine green angiographies decreased from 2.4% to 0.9%. In the same period, the yearly rate of intravitreal injection increased from 0.3% to 1.5%, and the use of laser photocoagulation decreased progressively from 2008 to 2014 (1.3% vs. 0.7%) but slightly increased from 2015 to 2017 (0.8% vs. 1.0%). Conclusions: Strategies to increase compliance with eye care recommendations are needed to improve early detection and management of diabetic eye complications. [ABSTRACT FROM AUTHOR]

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

Advanced glycation end products (AGEs) accumulated during long-term hyperglycemia are involved in diabetes complications and can be estimated by skin autofluorescence (sAF). During pregnancy, hyperglycemia exposes women to the risk of having a macrosomic newborn. The aim of this study was to determine whether sAF of women with diabetes during a singleton pregnancy could predict macrosomia in their newborns. Using an AGE Reader, we measured the sAF at the first visit of 343 women who were referred to our diabetology department during years 2011-2015. Thirty-nine women had pregestational diabetes, 95 early gestational diabetes mellitus (GDM), and 209 late GDM. Macrosomia was defined as birth weight ≥4,000 g and/or large for gestational age ≥90th percentile. Forty-six newborns were macrosomic. Their mothers had 11% higher sAF compared with other mothers: 2.03 ± 0.30 arbitrary units (AUs) vs. 1.80 ± 0.34 (P < 0.0001). Using multivariate logistic regression, the relation between sAF and macrosomia was significant (odds ratio 4.13 for 1-AU increase of sAF [95% CI 1.46-11.71]) after adjusting for several potential confounders. This relation remained significant after further adjustment for HbA1c (among 263 women with available HbA1c) and for women with GDM only. sAF of pregnant women with diabetes, a marker of long-term hyperglycemic exposure, predicts macrosomia in their newborns. [ABSTRACT FROM AUTHOR]

Objectives Advanced glycation end-products (AGEs) are involved in diabetic retinopathy (DR). Their accumulation in tissues can be analyzed by measuring the skin autofluorescence (sAF). We hypothesized that renal insufficiency, another cause of high sAF, may disturb the relation between sAF and DR. Research Design and Methods We measured sAF with an AGE-Reader in 444 patients with type 2 diabetes (T2D), and we analyzed their retinal status. The associations of sAF with DR, and interaction with renal insufficiency were estimated by multivariate logistic regression analysis. Results Mean age was 62 years (standard deviation (SD) 10 years), diabetes duration 13 (9) years and mean HbA1C 8.9% (1.8). The prevalence of DR was 21.4% and increased with age, diabetes duration, arterial hypertension, renal parameters (serum creatinine and albumin excretion rates), and sAF. The prevalence of macular edema (ME) was 8.6% and increased with the duration of diabetes, but not with sAF (p = 0.11). There was a significant interaction between renal insufficiency and sAF for the relation with DR or ME (p = 0.02). For the 83% patients without renal insufficiency (estimated GFR > 60 mL/min/1.73 m2), sAF was related to DR or ME after multivariate adjustment: OR 1.87 (1.09–3.19). The 17% patients with renal insufficiency had the highest rates of DR or ME (38.6%) and the highest sAF, unrelated to each other. Conclusions In T2D patients with renal insufficiency, the high sAF does not relate to retinopathy, which should be systematically searched due to its high frequency. For other patients, a high sAF argues for DR screening. [ABSTRACT FROM AUTHOR]

Background: Olive oil provides a mixture of lipids and antioxidant nutrients which may help preventing age-related diseases such as age-related macular degeneration (AMD). However, little is known about the associations between olive oil consumption and the risk of AMD. Objective: To examine associations between olive oil use and AMD prevalence in elderly subjects. Methods: Alienor (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) is a population-based study on eye diseases performed in elderly residents of Bordeaux (France). In 1999–2000, frequencies of consumption of main categories of dietary fats used were collected. In 2006–2088, AMD was graded from non mydriatic retinal photographs into three exclusive stages: no AMD, early AMD, and late AMD. Two categories of preferred dietary fat used (olive oil, n-3 rich oils, n-6 rich oils, mixed oils, butter and margarine) were defined: “no use” and “regular use” (using fat for spreading and/or cooking and/or dressing). Associations of AMD with each fat use were estimated using Generalized Estimating Equation logistic regressions models. Results: Our study included 654 subjects (1269 eyes) with complete data (n = 268 eyes with early AMD and n = 56 with late AMD). After adjustment for potential confounders, regular use of olive oil was significantly associated with a decreased risk of late AMD (odds ratio [OR] = 0.44, 95% confidence interval [CI]: 0.21;0.91). In contrast, regular use of olive oil was not significantly associated with early AMD (OR = 0.84, 95%CI: 0.59;1.21). No associations were found between regular consumption of n-3 rich oils, n-6 rich oils, mixed oils, butter and margarine and AMD, whatever the stage. Conclusions: This study suggests a protective effect of olive oil consumption for late AMD in this elderly community-dwelling population. Characterization of the mediating nutrients deserves further research. [ABSTRACT FROM AUTHOR]

Background: Elderly persons are at elevated risk of vitamin D deficiency, which is involved in various health problems. However, its relation with age-related macular degeneration (AMD) is debated. Objectives: We investigated factors associated with plasma 25-hydroxyvitamin D [25(OH)D] deficiency and the associations between plasma 25(OH)D concentrations and AMD in elderly subjects. Methods: Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes (ALIENOR) is a population-based study on eye diseases performed in elderly residents of Bordeaux, France. Plasma 25(OH)D concentrations were assessed from blood samples and categorized as <25 nmol/L (deficiency), 25-49 nmol/L (insufficiency), or ≥50 nmol/L (sufficiency). AMD was classified as: no AMD, early AMD, and late AMD. Associations between baseline characteristics and plasma 25(OH)D status were examined with multinomial logistic regression analysis. Associations between AMD and plasma 25(OH)D status were estimated using generalized estimating equation logistic regressions. Results: Six hundred ninety-seven subjects with complete data were included. The prevalence of plasma 25(OH)D deficiency and insufficiency were 27.3% and 55.9%, respectively. In multivariate analysis, 25(OH)D deficiency was significantly associated with older age (P = 0.0007), females (P = 0.0007), absence of physical activity (P = 0.01), absence of vitamin D supplementation (P < 0.0001), higher plasma total cholesterol (P = 0.007), use of fibrates (P < 0.0001), lower alcohol consumption (P = 0.02), and season of blood sampling (P < 0.0001 ). After adjustment for these covariates and dietary omega-3 polyunsaturated fatty acid intake, smoking, and body mass index, no significant associations were found between early AMD and 25(OH)D insufficiency or deficiency (OR: 0.71, P = 0.12; OR: 0.73, P = 0.23, respectively) or with late AMD (OR: 1.04, P = 0.93; OR: 0.74, P = 0.59, respectively). Conclusion: These findings underline the very high prevalence of plasma 25(OH)D deficiency in this elderly population but do not support a specific role for vitamin D in AMD. [ABSTRACT FROM AUTHOR]

Background: Lipid metabolism and particularly high-density lipoprotein (HDL) may be involved in the pathogenic mechanism of age-related macular degeneration (AMD). However, conflicting results have been reported in the associations of AMD with plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD. Methods: The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France). AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (n = 430 subjects, 938 eyes); large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, n = 176, 247); late AMD (n = 40, 61). Associations of AMD with plasma lipids (HDL, total cholesterol (TC), Low-density lipoprotein (LDL), and triglycerides (TG)) were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data. Results: After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261), higher HDL was significantly associated with an increased risk of early (OR = 2.45, 95%CI: 1.54–3.90; P = 0.0002) and any AMD (OR = 2.29, 95%CI: 1.46–3.59; P = 0.0003). Association with late AMD was far from statistical significance (OR = 1.58, 95%CI: 0.48–5.17; p = 0.45). No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use. Conclusions: This study suggests that elderly patients with high HDL concentration may be at increased risk for AMD and, further, that HDL dysfunction might be implicated in AMD pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Cataract, the leading cause of blindness worldwide, is a multifactorial disease involving oxidative stress mechanisms. The aim of our study was to investigate the relationship between air pollution exposure and the incidence of cataract surgery.The 3C‐Alienor study is a population‐based cohort of residents of Bordeaux, France, aged 65 years or more, recruited in 1999–2000 and followed every 2–3 years until 2017. Cataract surgery was self‐reported and checked at slit‐lamp by trained professionals. Average air pollution exposure (particulate matter ≤2.5 μm (PM2.5), black carbon (BC), nitrogen dioxide (NO2)) in the 10 years preceding baseline was estimated at the participants' geocoded residential address, using temporally adjusted land use regression. Associations of 10‐year average air pollution exposure with incidence of cataract were estimated using Cox proportional hazard models adjusted for confounders.The study included 829 subjects without cataract surgery prior to inclusion; the mean age at inclusion was 72.6 years (standard deviation (SD): 4.2) and 61% were women. The median (Interquartile‐range (IQR)) follow‐up duration was 14.1 (6.4) years during which 507 participants underwent cataract surgery. Exposure to a concentration ≥40 μg/m3 of NO2 (the current regulatory limit value in Europe) was associated with incident cataract surgery (HR = 1.46, CI (1.16, 1.84), p = 0.001). No statistically significant association was found with PM2.5 and BC.Long‐term exposure to a NO2 concentration ≥ 40 μg/m3 was associated with an increased incidence of cataract surgery. Complying with current European air pollution standards could reduce cataract surgery costs and improve population quality of life. [ABSTRACT FROM AUTHOR]

Age-related maculopathy susceptibility 2 (ARMS2) is considered the most enigmatic of the genes for age-related macular degeneration (AMD). We investigated the phenotypic course and spectrum of AMD for the risk haplotype at the ARMS2 and high-temperature requirement A serine peptidase 1 (HTRA1) locus in a large European consortium. Pooled analysis of 4 case-control and 6 cohort studies. Individuals (N = 17 204) aged 55 years or older participating in the European Eye Epidemiology consortium. Age-related macular degeneration features and macular thickness were determined on multimodal images; data on genetics and phenotype were harmonized. Risks of AMD features for rs3750486 genotypes at the ARMS2 / HTRA1 locus were determined by logistic regression and were compared with a genetic risk score (GRS) of 19 variants at the complement pathway. Lifetime risks were estimated with Kaplan–Meier analyses in population-based cohorts. Age-related macular degeneration features and stage. Of 2068 individuals with late AMD, 64.7% carried the ARMS2/HTRA1 risk allele. For homozygous carriers, the odds ratio (OR) of geographic atrophy was 8.6 (95% confidence interval [CI], 6.5–11.4), of choroidal neovascularization (CNV) was 11.2 (95% CI, 9.4–13.3), and of mixed late AMD was 12.2 (95% CI, 7.3–20.6). Cumulative lifetime risk of late AMD ranged from 4.4% for carriers of the nonrisk genotype to 9.4% and 26.8% for heterozygous and homozygous carriers. The latter received the diagnosis of late AMD 9.6 years (95% CI, 8.0–11.2) earlier than carriers of the nonrisk genotype. The risk haplotype was not associated with hard or soft drusen < 125 μm (OR, 1.2; 95% CI, 0.9–1.7), but risks increased significantly for soft drusen ≥ 125 μm (OR, 2.1; 95% CI, 1.5–3.0), up to an OR of 7.2 (95% CI, 3.8–13.8) for reticular pseudodrusen. Compared with persons with a high GRS for complement, homozygous carriers of ARMS2 / HTRA1 showed a higher risk of CNV (OR, 4.1; 95% CI, 3.2–5.4); risks of other characteristics were not different. Carriers of the risk haplotype at ARMS2/HTRA1 have a particularly high risk of late AMD at a relatively early age. Data suggest that risk variants at ARMS2/HTRA1 act as a strong catalyst of progression once early signs are present. The phenotypic spectrum resembles that of complement genes, only with higher risks of CNV. [ABSTRACT FROM AUTHOR]

Purpose To investigate associations of adherence to the Mediterranean diet (MeDi) with incidence of advanced age-related macular degeneration (AMD; the symptomatic form of AMD) in 2 European population-based prospective cohorts. Design Prospective cohort study of the Rotterdam Study I (RS-I) and the Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (Alienor) Study populations. Participants Four thousand four hundred forty-six participants 55 years of age or older from the RS-I (The Netherlands) and 550 French adults 73 years of age or older from the Alienor Study with complete ophthalmologic and dietary data were included in the present study. Methods Examinations were performed approximately every 5 years over a 21-year period (1990–2011) in RS-I and every 2 years over a 4-year period (2006–2012) in the Alienor Study. Adherence to the MeDi was evaluated using a 9-component score based on intake of vegetables, fruits, legumes, cereals, fish, meat, dairy products, alcohol, and the monounsaturated-to-saturated fatty acids ratio. Associations of incidence of AMD with MeDi were estimated using multivariate Cox proportional hazard models. Main Outcomes Measures Incidence of advanced AMD based on retinal fundus photographs. Results Among the 4996 included participants, 155 demonstrated advanced incident AMD (117 from the RS-I and 38 from the Alienor Study). The mean follow-up time was 9.9 years (range, 0.6–21.7 years) in the RS-I and 4.1 years (range, 2.5–5.0 years) in the Alienor Study. Pooling data for both the RS-I and Alienor Study, participants with a high (range, 6–9) MeDi score showed a significantly reduced risk for incident advanced AMD compared with participants with a low (range, 0–3) MeDi score in the fully adjusted Cox model (hazard ratio, 0.59; 95% confidence interval, 0.37–0.95; P = 0.04 for trend). Conclusions Pooling data from the RS-I and Alienor Study, higher adherence to the MeDi was associated with a 41% reduced risk of incident advanced AMD. These findings support the role of a diet rich in healthful nutrient-rich foods such as fruits, vegetables, legumes, and fish in the prevention of AMD. [ABSTRACT FROM AUTHOR]

As part of a healthy diet, higher carotenoid intakes have been associated with a reduced risk of depression, mainly in adults, while prospective studies on plasma carotenoids in older adults are lacking. The aim of this study was to assess the prospective association between plasma carotenoids and the risk of Depressive Symptomatology (DS) in older adults. The study sample was based on the Three-City cohort of adults aged 65y+ free from DS at enrollment in 1999. Plasma carotenoids were measured at baseline. DS was assessed every 2–3 years over 17 years and defined by a Center for Epidemiologic Studies-Depression Scale score ≥ 16 and/or by antidepressant use. The association between plasma carotenoids or carotenoid/lipids (cholesterol and triglycerides) ratio and the risk for DS was assessed through multiple random-effect logistic regression. The study sample was composed of 1010 participants (mean age 74 y (±4.9), 58 % of women) followed-up during a median time of 13.4 years. Plasma zeaxanthin and ratios of zeaxanthin/lipids, lutein+zeaxanthin/lipids and β-carotene/lipids were independently associated with a significant reduced risk of DS over time (Odds ratio (OR) = 0.81, 95 % Confidence Interval (CI) [0.67;0.99], OR = 0.79 [0.67;0.98], OR = 0.79 [0.64;0.94] and OR = 0.80 [0.66;0.97] for +1 standard deviation of each exposure respectively). Plasma carotenoids were only available at study baseline. Focusing on circulating carotenoids and considering lipids levels, the present results suggested an association between higher levels of plasma zeaxanthin, combined lutein+zeaxanthin and β-carotene and a decreased risk of DS over time in older adults. • Nutrition is a promising approach in relation to depression in older adults. • Studies on circulating levels of carotenoid are lacking. • This study was based on prospective design, large sample size and long follow-up. • Higher plasma zeaxanthin or β-carotene reduced the risk of depressive symptomatology. • These results encouraged to eat a large variety of colorful fruits and vegetables. [ABSTRACT FROM AUTHOR]

To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium. The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants. We examined associations of 4 categories of systemic medications—antihypertensive medications (β-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications—with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only. Glaucoma prevalence and IOP. In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic β-blockers was associated with a lower IOP (β coefficient, −0.33 mmHg; 95% CI, −0.57 to −0.08 mmHg). Monotherapy of both selective systemic β-blockers (β coefficient, −0.45 mmHg; 95% CI −0.74 to −0.16 mmHg) and nonselective systemic β-blockers (β coefficient, −0.54 mmHg; 95% CI, −0.94 to −0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (β coefficient, −0.30 mmHg; 95% CI, −0.47 to −0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP. We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic β-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a common multifactorial disease in the elderly with a prominent genetic basis. Many risk variants have been identified, but the interpretation remains challenging. We investigated the genetic distribution of AMD-associated risk variants in a large European consortium, calculated attributable and pathway-specific genetic risks, and assessed the influence of lifestyle on genetic outcomes. Pooled analysis of cross-sectional data from the European Eye Epidemiology Consortium. Seventeen thousand one hundred seventy-four individuals 45 years of age or older participating in 6 population-based cohort studies, 2 clinic-based studies, and 1 case-control study. Age-related macular degeneration was diagnosed and graded based on fundus photographs. Data on genetics, lifestyle, and diet were harmonized. Minor allele frequencies and population-attributable fraction (PAF) were calculated. A total genetic risk score (GRS) and pathway-specific risk scores (complement, lipid, extra-cellular matrix, other) were constructed based on the dosage of SNPs and conditional β values; a lifestyle score was constructed based on smoking and diet. Intermediate and late AMD. The risk variants with the largest difference between late AMD patients and control participants and the highest PAFs were located in ARMS2 (rs3750846) and CHF (rs570618 and rs10922109). Combining all genetic variants, the total genetic risk score ranged from –3.50 to 4.63 and increased with AMD severity. Of the late AMD patients, 1581 of 1777 (89%) showed a positive total GRS. The complement pathway and ARMS2 were by far the most prominent genetic pathways contributing to late AMD (positive GRS, 90% of patients with late disease), but risk in 3 pathways was most frequent (35% of patients with late disease). Lifestyle was a strong determinant of the outcome in each genetic risk category; unfavorable lifestyle increased the risk of late AMD at least 2-fold. Genetic risk variants contribute to late AMD in most patients. However, lifestyle factors have a strong influence on the outcome of genetic risk and should be a strong focus in patient management. Genetic risks in ARMS2 and the complement pathway are present in most late AMD patients but are mostly combined with risks in other pathways. [ABSTRACT FROM AUTHOR]

Adjusted differences black squares and 95% confidence intervals (CIs) (horizontal lines) of observed and predicted retinal -3 PUFAs contents for age-related macular degeneration in donor eyes and humans patients. Interestingly, cholesteryl esters species with -3 PUFAs contributed positively to the estimation of retinal -3 PUFAs content whereas those with -6 PUFAs lowered the prediction index, which is consistent with the well-established competitive metabolism of -3 and -6 PUFAs. Current treatments for age-related macular degeneration (AMD)-the leading cause of blindness in industrialized countries-are restricted to a single form of the disease and cannot always avoid severe visual loss.1 Among emerging preventive strategies, -3 polyunsaturated fatty acids (PUFAs) are enjoying interest as they promote normal retinal structure and function, reduce incidence, and slow progression of AMD, consistently with their abundance in retinal neurons. [Extracted from the article]

Purpose Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Design Pooled analysis of cross-sectional data. Participants Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. Methods AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. Main Outcome Measures AMD features and stage; lipid measurements. Results HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14–1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91–0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10–1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10–7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10–6 and P = 1.6 × 10–4). Conclusions Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered. [ABSTRACT FROM AUTHOR]

Purpose To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. Design Cross-sectional meta-analysis. Participants A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9±12.3–82.1±4.2 years) of the European Eye Epidemiology (E3) consortium. Methods We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. Main Outcome Measures Determinants of pRNFLT. Results Mean pRNFLT ranged from 86.8±21.4 μm in the Rotterdam Study I to 104.7±12.5 μm in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (β = –0.38 μm/year; 95% confidence interval [CI], –0.57 to –0.18), higher intraocular pressure (IOP) (β = –0.36 μm/mmHg; 95% CI, –0.56 to –0.15), visual impairment (β = –5.50 μm; 95% CI, –9.37 to –1.64), and history of systemic hypertension (β = –0.54 μm; 95% CI, –1.01 to –0.07) and stroke (β = –1.94 μm; 95% CI, –3.17 to –0.72). A suggestive, albeit nonsignificant, association was observed for dementia (β = –3.11 μm; 95% CI, –6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (β = 1.39 μm/diopter; 95% CI, 1.19–1.59) and smoking (β = 1.53 μm; 95% CI, 1.00–2.06 for current smokers compared with never-smokers). Conclusions In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities. [ABSTRACT FROM AUTHOR]

Chronic exposure to air pollution may have adverse effects on neurodegenerative diseases. Glaucoma, the second leading cause of blindness worldwide, is a neurodegenerative disease of the optic nerve, characterized by progressive thinning of the retinal nerve fiber layer (RNFL). We investigated the relationship of air pollution exposure with longitudinal changes of RNFL thickness in the Alienor study, a population-based cohort of residents of Bordeaux, France, aged 75 years or more. Peripapillary RNFL thickness was measured using optical coherence tomography imaging every 2 years from 2009 to 2020. Measurements were acquired and reviewed by specially trained technicians to control quality. Air pollution exposure (particulate matter ≤2.5 μm (PM 2.5), black carbon (BC), nitrogen dioxide (NO 2)) was estimated at the participants' geocoded residential address using land-use regression models. For each pollutant, the 10-year average of past exposure at first RNFL thickness measurement was estimated. Associations of air pollution exposure with RNFL thickness longitudinal changes were assessed using linear mixed models adjusted for potential confounders, allowing for intra-eye and intra-individual correlation (repeated measurements). The study included 683 participants with at least one RNFL thickness measurement (62% female, mean age 82 years). The average RNFL was 90 μm (SD:14.4) at baseline. Exposure to higher levels of PM 2.5 and BC in the previous 10 years was significantly associated with a faster RNFL thinning during the 11-year follow-up (−0.28 μm/year (95% confidence interval (CI) [-0.44;-0.13]) and −0.26 μm/year (95% CI [-0.40;-0.12]) per interquartile range increment; p < 0.001 for both). The size of the effect was similar to one year of age in the fitted model (−0.36 μm/year). No statistically significant associations were found with NO 2 in the main models. This study evidenced a strong association of chronic exposure to fine particulate matter with retinal neurodegeneration, at air pollution levels below the current recommended thresholds in Europe. • Fine particulate matter exposure is associated with a faster RNFL thinning over time. • The effect of air pollution on RNFL loss was similar to the effect of age. • The effect of pollutants was observed below the current European regulatory limit. • These suggests a possible association between air pollution exposure and glaucoma. [ABSTRACT FROM AUTHOR]

La dépression est un problème majeur de santé publique, particulièrement chez les personnes âgées. La nutrition est un mode de vie modifiable qui pourrait potentiellement prévenir le risque de dépression. Dans le cadre d'une alimentation saine, un apport plus élevé en caroténoïdes a déjà été associé à une réduction du risque de dépression, mais les études prospectives sur les niveaux circulants de caroténoïdes chez les personnes âgées font défaut. L'objectif de cette étude était d'évaluer l'association prospective entre les caroténoïdes plasmatiques et l'incidence de la symptomatologie dépressive (SD) chez des adultes âgés. L'échantillon d'étude était basé sur la cohorte prospective des Trois cités (3C), composé d'adultes âgés de 65 ans et plus habitant Bordeaux ou Montpellier, exempts de symptomatologie dépressive (SD) à l'inclusion en 1999. Les caroténoïdes plasmatiques ont été mesurés à l'inclusion par méthode analytique de chromatographie liquide à haute performance et les ratios caroténoïdes plasmatiques/(triglycérides + cholestérol total) ont été calculés. La SD a été évaluée tous les 2 à 3 ans pendant le suivi d'une durée maximale de 17 ans et définie comme un score ≥ 16 sur l'échelle Center for Epidemiologic Studies-Depression et/ou par la prise d'un traitement antidépresseur. Les associations entre caroténoïdes ou ratios caroténoïdes/lipides et l'incidence de SD ont été évaluées par des modèles de régression logistique à effets aléatoires ajustés sur les potentiels facteurs de confusion, dont l'âge, le statut tabagique, l'activité physique, l'indice de masse corporelle et les comorbidités. Les données de 1010 participants (860 à Bordeaux et 150 à Montpellier, 585 femmes, âge moyen 74 ans [±4,9]) avec un suivi médian de 13,8 années ont été analysés. La concentration plasmatique moyenne des caroténoïdes totaux était de 1085 μg/L (±545) et une SD a été identifiée chez 436 participants au cours du suivi. La zéaxanthine plasmatique et les ratios de zéaxanthine/lipides, de β -carotène/lipides et de lutéine + zéaxanthine/lipides étaient indépendamment associés à une réduction du risque de SD au cours du temps après prise en compte des potentiels facteurs de confusion (rapport de côte (RC) = 0,81, intervalle de confiance à 95 % [0,67 ; 0,99], RC = 0,79 [0,67 ; 0,94], RC = 0,79 [0,64 ; 0,98] et RC = 0,80 [0,66 ; 0,97] respectivement pour une augmentation d'un écart-type de zéaxanthine, du ratio de zéaxanthine/lipides, de β -carotène/lipides et de lutéine + zéaxanthine/lipides). En se concentrant sur les niveaux circulants, les résultats suggèrent une association inverse entre la zéaxanthine plasmatique, le β -carotène et la combinaison lutéine + zéaxanthine et le risque de SD au cours du temps chez les personnes âgées en utilisant une méthode pertinente pour des données répétées sur un long suivi. Une meilleure compréhension des mécanismes sous-jacents mérite des recherches supplémentaires. [ABSTRACT FROM AUTHOR]

The authors discuss a report about the risk factors for neonatal hypoglycaemia in 767 women with gestational diabetes mellitus (GDM). Topics mentioned include intrauterine epigenetic modifications driven by early hyperglycaemia, an increase in advanced glycation end-products from no diabetes to early and regular GDM, and attributes of mothers with gestational diabetes according to the presence of neonatal hypoglycaemia in their newborn.

Purpose To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. Design Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E 3 ) Consortium. Participants The E 3 Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. Methods Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤−0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. Main Outcome Measures Variation in age-specific myopia prevalence for differing years of birth and educational level. Results There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6–18.1) to 23.5% (95% CI, 23.2–23.7) in those born between 1910 and 1939 compared with 1940 and 1979 ( P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0–25.8), 29.1% (CI, 28.8–29.5), and 36.6% (CI, 36.1–37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio–2.43 (CI, 1.26–4.17) and 2.62 (CI, 1.31–5.00), respectively—whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21–6.57). Conclusions Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia. [ABSTRACT FROM AUTHOR]