Plasma Vitamin D and Intermediate Age-Related Macular Degeneration: Insights from the Longitudinal ALIENOR Study
Abstract
Background Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, with limited options to prevent disease progression. Vitamin D may influence AMD pathogenesis through anti-inflammatory, antioxidative, and anti-angiogenic effects. This study aims to investigate the association between deseasonalized plasma 25-hydroxyvitamin D levels and the risk of incident AMD, as well as longitudinal changes in macular layer thickness in an elderly population. Design Population-based cohort study. Participants 700 eyes from 429 participants aged ≥ 65 years from the Alienor Study, followed over up to 18 years. Methods Baseline deseasonalized plasma 25-hydroxyvitamin D levels were measured and categorized as sufficient (≥ 50 nmol/l), insufficient (25 - 49 nmol/l), or deficient (< 25 nmol/l). Cox proportional hazards models adjusted for demographic, lifestyle, and clinical covariates were used to estimate the risk of incident AMD. Longitudinal linear mixed-effects models assessed changes in outer retinal layer thicknesses derived from OCT imaging. Main Outcome Measures: Incident intermediate and advanced AMD based on fundus color photographs and OCT. Results Mean baseline deseasonalized plasma 25-hydroxyvitamin D level was 37.9 ± 14.9 nmol/l. Vitamin D deficiency (< 25 nmol/l) was significantly associated with increased risk of incident intermediate AMD compared to sufficient levels (≥ 50 nmol/l, HR = 2.34; 95% CI: 1.19 - 4.61; p = 0.01), while insufficiency (25 - 49 nmol/l) showed a borderline increased risk (HR = 1.74; 95% CI: 0.98 - 3.08; p = 0.06). No significant associations were observed with advanced AMD. Vitamin D-deficient participants also experienced a significant increase in retinal pigment epithelium–Bruch’s membrane (RPE–BM) complex thickness over time (β = 0.07 μm/year; 95% CI: 0.01 - 0.13; p = 0.02), while other outer retinal layers showed no significant change. Conclusions Low deseasonalized plasma 25-hydroxyvitamin D levels were associated with a higher risk of developing intermediate AMD and progressive thickening of the RPE–BM complex, a key retinal structure implicated in AMD pathogenesis. These findings support an association hypothesis and highlight vitamin D status as a candidate modifiable factor worthy of further investigation.
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BibTeX
@article{larsen2026plasma,
title = {{Plasma Vitamin D and Intermediate Age-Related Macular Degeneration: Insights from the Longitudinal ALIENOR Study}},
author = {Petra P. Larsen and Marie-Noëlle Delyfer and Jean-François Korobelnik and Cécile Delcourt and Bénédicte M. J. Merle},
journal = {Ophthalmology Science},
year = {2026},
month = oct,
doi = {10.1016/j.xops.2026.101364},
url = {https://hal.science/hal-05784432v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Plasma Vitamin D and Intermediate Age-Related Macular Degeneration: Insights from the Longitudinal ALIENOR Study
AU - Petra P. Larsen
AU - Marie-Noëlle Delyfer
AU - Jean-François Korobelnik
AU - Cécile Delcourt
AU - Bénédicte M. J. Merle
PY - 2026
DA - 2026/10/07
JO - Ophthalmology Science
DO - 10.1016/j.xops.2026.101364
UR - https://hal.science/hal-05784432v1
AB - Background Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, with limited options to prevent disease progression. Vitamin D may influence AMD pathogenesis through anti-inflammatory, antioxidative, and anti-angiogenic effects. This study aims to investigate the association between deseasonalized plasma 25-hydroxyvitamin D levels and the risk of incident AMD, as well as longitudinal changes in macular layer thickness in an elderly population. Design Population-based cohort study. Participants 700 eyes from 429 participants aged ≥ 65 years from the Alienor Study, followed over up to 18 years. Methods Baseline deseasonalized plasma 25-hydroxyvitamin D levels were measured and categorized as sufficient (≥ 50 nmol/l), insufficient (25 - 49 nmol/l), or deficient (< 25 nmol/l). Cox proportional hazards models adjusted for demographic, lifestyle, and clinical covariates were used to estimate the risk of incident AMD. Longitudinal linear mixed-effects models assessed changes in outer retinal layer thicknesses derived from OCT imaging. Main Outcome Measures: Incident intermediate and advanced AMD based on fundus color photographs and OCT. Results Mean baseline deseasonalized plasma 25-hydroxyvitamin D level was 37.9 ± 14.9 nmol/l. Vitamin D deficiency (< 25 nmol/l) was significantly associated with increased risk of incident intermediate AMD compared to sufficient levels (≥ 50 nmol/l, HR = 2.34; 95% CI: 1.19 - 4.61; p = 0.01), while insufficiency (25 - 49 nmol/l) showed a borderline increased risk (HR = 1.74; 95% CI: 0.98 - 3.08; p = 0.06). No significant associations were observed with advanced AMD. Vitamin D-deficient participants also experienced a significant increase in retinal pigment epithelium–Bruch’s membrane (RPE–BM) complex thickness over time (β = 0.07 μm/year; 95% CI: 0.01 - 0.13; p = 0.02), while other outer retinal layers showed no significant change. Conclusions Low deseasonalized plasma 25-hydroxyvitamin D levels were associated with a higher risk of developing intermediate AMD and progressive thickening of the RPE–BM complex, a key retinal structure implicated in AMD pathogenesis. These findings support an association hypothesis and highlight vitamin D status as a candidate modifiable factor worthy of further investigation.
SN - 2666-9145
ER -