Plasma Vitamin D and Intermediate Age-Related Macular Degeneration: Insights from the Longitudinal ALIENOR Study

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 antiangiogenic effects. This study aims to investigate the association between deseasonalized plasma 25-hydroxyvitamin D [25(OH)D] levels and the risk of incident AMD, as well as longitudinal changes in macular layer thickness in an elderly population.

Population-based cohort study.

Seven hundred eyes from 429 participants aged ≥65 years from the ALIENOR Study, followed up over 18 years.

Baseline deseasonalized plasma 25(OH)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.

Incident intermediate and advanced AMD based on fundus color photographs and OCT.

The mean baseline deseasonalized plasma 25(OH)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, hazard ratio [HR] = 2.34; 95% confidence interval [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 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.

Low deseasonalized plasma 25(OH)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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