Association of long-term exposure to ambient air pollution with retinal neurodegeneration: the prospective Alienor study.

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 (PM2.5), black carbon (BC), nitrogen dioxide (NO2)) 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 PM2.5 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 NO2 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.

Associations of circulating vitamins with 10-year retinal neurodegeneration: the Alienor Study.

OBJECTIVE: To investigate the associations between circulating vitamins A, D, E, B6, B9, B12 and longitudinal changes in retinal nerve fiber layer (RNFL) thickness. METHODS: The Alienor study, a prospective population-based cohort (Bordeaux, France), includes 963 individuals aged 73 years or older at baseline. The present study included 646 participants with complete RNFL measurement and vitamins. Study period is from 2009 to 2020. Peripapillary RNFL thickness was measured using spectral domain optical coherence tomography (SD-OCT). Plasma vitamins A, D and E and, serum vitamins B6, B9 and B12 were measured from blood sample. We performed linear mixed models, adjusted for age, gender, axial length, family history of glaucoma, and alcohol consumption to evaluated associations between vitamins and RNFL thickness changes over time. RESULTS: Individuals having higher concentrations of vitamin E, D and B9 had a slower RNFL thinning during the 10-years of follow-up. Indeed, a 1-standard deviation (SD) increase of vitamin E (10.8 µmol/L), D (17.6 nmol/L) and B9 (11 µmol/L) were associated with slower RNFL thinning by 0.14 µm/year (95% confidence interval (CI), 0.03-0.25, p = 0.01), 0.14 µm/year (95% CI, 0.02-0.27, p = 0.02) and 0.11 µm/year (95% CI: 0.007-0.21, p = 0.04), respectively. No significant associations were observed for vitamins A, B6 and B12 with RNFL thinning. CONCLUSIONS: Higher levels of vitamins E, D and B9 were associated with a slower RNFL thickness on SD-OCT over time, suggesting that those vitamins may contribute to the neuroprotection of the retina.

Association of Age-Related Macular Degeneration with a Blood Biomarker of Lipopolysaccharide, a Gut Bacterial Proinflammatory Toxin.

Purpose: Chronic inflammation, immune dysregulation, and oxidative stress are major drivers of age-related macular degeneration (AMD) pathogenesis. Lipopolysaccharide (LPS) is a potent proinflammatory toxin originating from gut bacteria. We assessed the association of a blood biomarker of LPS exposure with incident AMD. Methods: The Alienor Study is a prospective population-based study, including 963 residents of Bordeaux (France), aged 73 years or more at baseline. Esterified 3-hydroxy fatty acids (3-OH FAs) were measured from blood samples as a proxy of LPS burden. AMD was graded from color retinal photographs and spectral domain optical coherence tomography, performed every two years from 2006 to 2017. Cox proportional hazards models were used to estimate associations of between esterified 3-OH FAs, using 722 eyes at risk for incident early AMD and 981 eyes at risk for incident advanced AMD. Results: Higher esterified 3-OH FAs were associated with incident early AMD after adjusting for age and gender (hazard ratio [HR] = 1.21 for 1 standard deviation [SD] increase; 95% confidence interval [CI], 1.01-1.45; P = 0.04) but not with incident advanced AMD (HR = 1.03 for 1 SD increase; 95% CI, 0.73-1.45; P = 0.86). These associations remained stable after multivariate adjustment and imputation for missing covariates (early AMD HR = 1.22 for 1 SD increase; 95% CI, 1.01-1.46; P = 0.04; advanced AMD HR = 0.98 for 1 SD increase; 95% CI, 0.69-1.38; P = 0.91). Conclusions: This study evidenced an association between higher esterified 3-OH FAs and incident early AMD, suggesting that exposure to LPS may be involved in the early pathophysiological processes of AMD.

Association of Lipopolysaccharide-Type Endotoxins with Retinal Neurodegeneration: The Alienor Study.

Purpose: Lipopolysaccharide (LPS)-type endotoxins are naturally found in the gut microbiota and there is emerging evidence linking gut microbiota and neuroinflammation leading to retinal neurodegeneration. Thinning of the retinal nerve fiber layer (RNFL) is a biomarker of retinal neurodegeneration, and a hallmark of glaucoma, the second leading cause of blindness worldwide. We assessed the association of a blood biomarker of LPS with peripapillary RNFL thickness (RNFLT) and its longitudinal evolution up to 11 years. Design: The Alienor study is a single center prospective population-based cohort study. Subjects: The studied sample of this study includes 1062 eyes of 548 participants receiving ≥1 gradable RNFL measurement. Methods: Plasma esterified 3-hydroxy fatty acids (3-OH FAs) were measured as a proxy of LPS burden. Retinal nerve fiber layer thickness was acquired using spectral-domain OCT imaging every 2 years from 2009 to 2020 (up to 5 visits). Main Outcome Measures: Associations of plasma esterified 3-OH FAs with RNFLT were assessed using linear mixed models. Results: Mean age of the included 548 participants was 82.4 ± 4.3 years and 62.6% were women. Higher plasma esterified 3-OH FAs was significantly associated with thinner RNFLT at baseline (coefficient beta = -1.42 microns for 1 standard deviation-increase in 3-OH FAs, 95% confidence interval [-2.56; -0.28], P = 0.02). This association remained stable after multivariate adjustment for potential confounders. No statistically significant association was found between 3-OH FAs and longitudinal RNFLT change. Conclusions: Higher plasma esterified 3-OH FAs were associated with thinner RNFLT at baseline, indicating an involvement of LPS in the early processes of optic nerve neurodegeneration and highlighting the potential importance of the human microbiota in preserving retinal health. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.