Associations of biomechanical properties of the cornea with environmental and metabolic factors in an elderly population : the ALIENOR study

PURPOSE: The purpose of this study was to assess the associations of biomechanical properties of the cornea with metabolic and environmental factors in an elderly population. METHODS: The ALIENOR (Antioxydants, Lipides Essentiels, Nutrition, and Maladies OculaiRes) study is a population-based study. In 2009-2010, 624 subjects, aged 74 years or more, underwent an eye examination, including intraocular pressure (IOP), central corneal thickness (CCT), and biomechanical properties of the cornea measurements using the Ocular Response Analyzer. Socio-demographic, lifestyle, and medical history data were collected using standardized questionnaires. Mean lifetime ambient ultraviolet (UV) exposure was estimated using residential history and statistics of UV radiation at each location using the Eurosun UV database. RESULTS: Mean age was 82.2 ± 4.3 years. Mean corneal hysteresis (CH), corneal resistance factor (CRF), and CCT were 9.4 ± 1.9, 9.8 ± 1.9 mm Hg, and 551.6 ± 36.8 μm, respectively. In the multivariate analysis, CH and CRF values were significantly lower in subjects older than 80 years (-0.56; 95% confidence interval [CI]: -0.89;-0.24); P < 0.001 and -0.48; 95% CI: -0.75;-0.20; P < 0.001, respectively), in subjects having higher ambient UV exposure (-0.50; 95% CI: -0.88;-0.12; P < 0.01; and -0.46; 95% CI: -0.78;-0.13); P < 0.05, respectively), and in subjects with high plasma LDL cholesterol (CH: -0.46; 95% CI: -0.86;-0.03; P < 0.05; and CRF: -0.37; 95% CI: -0.72;-0.008; P < 0.05). Central corneal thickness was significantly higher in former smokers than in never smokers (+11.01; 95% CI: 0.48;21.55; P < 0.05) and was not significantly associated with age, ambient UV exposure, diabetes, or LDL cholesterol. CONCLUSIONS: Biomechanical properties of the cornea are modified by metabolic and lifetime environmental factors, especially UV exposure. The manner these factors may influence onset and progression of ocular diseases or IOP measurements need further investigation

Mediterranean Diet Adherence and Risk of Depressive Symptomatology in a French Population-Based Cohort of Older Adults

Several foods from the Mediterranean Diet (MeDi) have already been characterized as beneficial for depression risk, while studies focusing on adherence to the overall MeDi are lacking among older adults at higher risk of depression. The aim of this study was to assess the association between MeDi adherence and the risk of depressive symptomatology (DS) in an older French cohort followed for 15 years. Participants from the Three-City Bordeaux cohort answered a food frequency questionnaire used to assess their MeDi adherence. The Center for Epidemiologic Studies Depression (CES-D) scale score of 16 or greater and/or use of antidepressant treatment ascertained at each visit defined incident DS. Random-effect logistic regression models were adjusted for potential confounders. Among 1018 participants, aged 75.6 years (SD 4.8 years) on average at baseline, 400 incident cases of DS were identified during the follow-up. Only when restricting the definition of DS to a CES-D score ≥ 16 was a borderline-significant trend towards a benefit of greater adherence to the MeDi with reduced odds of DS found (p-value = 0.053). In this large sample of older French adults, a potential benefit of greater adherence to the MeDi regarding the risk of DS would depend on the definition of DS

Invest Ophthalmol Vis Sci

Purpose: To analyze the association between skin autofluorescence (sAF), estimating tissue accumulation of advanced glycation end-products (AGEs), and open angle glaucoma (OAG) in an elderly population. Methods: The Antioxydants, Lipides Essentiels, Nutrition and maladies OculaiRes (ALIENOR) study is an on-going epidemiologic population-based study on age-related eye diseases. In 2009 to 2010, 624 subjects, aged 74 years or older, were recruited. All subjects underwent a complete eye examination, including optic disc color photography and spectral-domain optical coherence tomography (SD-OCT) examination. Sociodemographic and medical history data were collected using standardized questionnaires. Glaucoma diagnosis was made using optic nerve head retinophotography and International Society for Epidemiologic and Geographical Ophthalmology criteria. sAF was measured with a noninvasive autofluorescence reader in 467 subjects. Results: Of subjects, 455 had complete data, 424 were classified as controls, and 31 classified as OAG. Mean age was 82.3 +/- 4.3 years, mean and median sAF were 2.8 +/- 0.7 and 2.7 arbitrary units (AU), respectively. In a multivariate analysis, higher sAF values (>/=2.7 AU) were associated with OAG (odds ratio [OR] = 2.28, 95% Confidence Interval [CI]: 1.03; 5.04). Other variables significantly associated with OAG were age (OR = 1.10, 95%CI: 1.00; 1.21), glaucoma family history (OR = 2.83, 95%CI: 1.14; 7.01) and smoking (1-20 pack-years [OR = 3.31, 95%CI: 1.18; 9.26]; >/=20 pack-years [OR = 3.85, 95%CI: 1.42; 10.46]). Conclusions: Higher level of sAF, which may act as a long-term biomarker of metabolic memory, and smoking are independently associated with an increased risk of glaucoma. Long-term accumulation of AGEs, a marker of oxidative stress, could play a role in the pathogenesis of glaucomatous chronic optic neuropathy

Plasma Lutein, a Nutritional Biomarker for Development of Advanced Age-Related Macular Degeneration: The Alienor Study

Lutein and zeaxanthin may lower the risk of age-related macular degeneration (AMD). We evaluated the associations of plasma lutein and zeaxanthin with the incidence of advanced AMD in the Alienor study (Antioxydants Lipides Essentiels Nutrition et Maladies Oculaires). Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006-2008). The present study included 609 participants with complete ophthalmologic and plasma carotenoids data. Examinations were performed every two years over an eight-year period (2006 to 2017). Plasma lutein and zeaxanthin were determined at baseline from fasting blood samples using high-performance liquid chromatography. Cox proportional hazard models were used to assess associations between plasma lutein, zeaxanthin, and their (total cholesterol (TC) + triglycerides (TG)) ratios with AMD. Among the 609 included participants, 54 developed advanced incident AMD during a median follow-up time of 7.6 years (range 0.7 to 10.4). Participants with higher plasma lutein had a reduced risk for incident advanced AMD in the fully adjusted model (HR = 0.63 per 1-SD increase (95% CI, 0.41-0.97), p = 0.03). A similar association was observed using the lutein/(TC + TG) ratio (HR = 0.59 (95% CI, 0.39-0.90), p = 0.01). No associations were evidenced for other carotenoids. Higher plasma lutein was associated with a 37% reduced risk of incident advanced AMD

Ophthalmology

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

Ophthalmology

PURPOSE: Age-related macular degeneration(AMD) is a common multifactorial disease in elderly with a prominent genetic basis. Many risk variants have been identified, but the interpretation is still 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. DESIGN: Pooled analysis of cross-sectional data from the E3 consortium. PARTICIPANTS: 17.174 individuals aged 45+ participating in 6 population-based cohort studies, 2 clinic based studies, 1 case-control study. METHODS: AMD was diagnosed and graded based on fundus photographs. Data on genetics, lifestyle, and diet were harmonized and completed where necessary. Minor allele frequencies and population attributable fraction (PAF) were calculated per single nucleotide polymorphism (SNP). 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 beta's; a lifestyle score was constructed based on smoking and dietary intake. RESULTS: The risk variants with the largest difference between late AMD cases and controls, and the highest PAFs were located in ARMS2 (rs3750846) and CHF (rs570618 and rs10922109). Both risk increasing and protective variants had the highest PAFs. Combining all genetic variants, the total genetic risk score ranged from -3.50 to 4.63, was normally distributed and increased with AMD severity. Of the late AMD cases, 1581/1777 (89%) had 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 late cases), but risk in three pathways was most frequent (35% of late cases). Lifestyle was a strong determinant of the outcome in each genetic risk category; unfavorable lifestyle increased the risk of late AMD at least twofold. CONCLUSIONS: Genetic risk variants contribute to late AMD in the majority of cases. 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 the majority of late AMD, but are mostly combined with risks in other pathways

Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia

Ophthalmology

OBJECTIVE: In the current study we aimed to identify metabolites associated with age-related macular degeneration (AMD) by performing the largest metabolome association analysis in AMD to date. In addition, we aimed to determine the effect of AMD-associated genetic variants on metabolite levels, and aimed to investigate associations between the identified metabolites and activity of the complement system, one of the main AMD-associated disease pathways. DESIGN: Case-control assocation analysis of metabolomics data. SUBJECTS: 2,267 AMD cases and 4,266 controls from five European cohorts. METHODS: Metabolomics was performed using a high-throughput H-NMR metabolomics platform, which allows the quantification of 146 metabolite measurements and 79 derivative values. Metabolome-AMD associations were studied using univariate logistic regression analyses. The effect of 52 AMD-associated genetic variants on the identified metabolites was investigated using linear regression. In addition, associations between the identified metabolites and activity of the complement pathway (defined by the C3d/C3 ratio) were investigated using linear regression. MAIN OUTCOME MEASURES: Metabolites associated with AMD RESULTS: We identified 60 metabolites that were significantly associated with AMD, including increased levels of large and extra-large HDL subclasses and decreased levels of VLDL, amino acids and citrate. Out of 52 AMD-associated genetic variants, seven variants were significantly associated with 34 of the identified metabolites. The strongest associations were identified for genetic variants located in or near genes involved in lipid metabolism (ABCA1, CETP, APOE, LIPC) with metabolites belonging to the large and extra-large HDL subclasses. In addition, 57 out of 60 metabolites were significantly associated with complement activation levels, and these associations were independent of AMD status. Increased large and extra-large HDL levels and decreased VLDL and amino acid levels were associated with increased complement activation. CONCLUSIONS: Lipoprotein levels were associated with AMD-associated genetic variants, while decreased essential amino acids may point to nutritional deficiencies in AMD. We observed strong associations between the vast majority of the AMD-associated metabolites and systemic complement activation levels, independent of AMD status. This may indicate biological interactions between the main AMD disease pathways, and suggests that multiple pathways may need to be targeted simultaneously for successful treatment of AMD

PLoS One

Age-related macular degeneration (AMD) is a common, progressive multifactorial vision-threatening disease and many genetic and environmental risk factors have been identified. The risk of AMD is influenced by lifestyle and diet, which may be reflected by an altered metabolic profile. Therefore, measurements of metabolites could identify biomarkers for AMD, and could aid in identifying high-risk individuals. Hypothesis-free technologies such as metabolomics have a great potential to uncover biomarkers or pathways that contribute to disease pathophysiology. To date, only a limited number of metabolomic studies have been performed in AMD. Here, we aim to contribute to the discovery of novel biomarkers and metabolic pathways for AMD using a targeted metabolomics approach of 188 metabolites. This study focuses on non-advanced AMD, since there is a need for biomarkers for the early stages of disease before severe visual loss has occurred. Targeted metabolomics was performed in 72 patients with early or intermediate AMD and 72 control individuals, and metabolites predictive for AMD were identified by a sparse partial least squares discriminant analysis. In our cohort, we identified four metabolite variables that were most predictive for early and intermediate stages of AMD. Increased glutamine and phosphatidylcholine diacyl C28:1 levels were detected in non-advanced AMD cases compared to controls, while the rate of glutaminolysis and the glutamine to glutamate ratio were reduced in non-advanced AMD. The association of glutamine with non-advanced AMD corroborates a recent report demonstrating an elevated glutamine level in early AMD using a different metabolomics technique. In conclusion, this study indicates that metabolomics is a suitable method for the discovery of biomarker candidates for AMD. In the future, larger metabolomics studies could add to the discovery of novel biomarkers in yet unknown AMD pathways and expand our insights in AMD pathophysiology