Findings from a recent study published in Frontiers in Medicine evaluated the causal relationships between Vitamin D levels and various ocular disorders.
Give me some background.
Vitamin D plays an important role in biological pathways, such as immune regulation, cell growth, and inhibition of apoptosis and anti-angiogenesis.
- In the liver, Vitamin D2 and D3 undergo hydroxylation to convert them to 25-hydroxyvitamin D (25[OH]D).
The serum level of 25(OH)D is considered a reliable marker of Vitamin D status and reflects skin production, dietary intake, and supplementation.
And the research into this thus far?
Previous studies have demonstrated varying associations between Vitamin D levels and ocular disorders, including:
- Myopia
- Diabetic retinopathy (DR)
- Retinal vein occlusion (RVO)
- Age-related macular degeneration (AMD)
- Note: There is some controversy and conflicting results from clinical investigations on whether Vitamin D level relates to AMD progression.
Now talk about the study.
In this cross-sectional study, investigators obtained independent genetic variables from genome-wide association studies (GWAS) and publicly available databases.
- The summary statistics for 25(OH)D levels were analyzed from two large-scale GWAS with sample sizes of 324,105 and 417,580 European patients.
The genetic variants of the ocular disorders listed below were extracted from the latest release of the FinnGen consortium:
- Myopia
- Primary open-angle glaucoma (POAG)
- Anterior iridocyclitis
- Senile cataract
- DR
- RVO
- Wet AMD
- Optic neuritis
And then?
Researchers performed bidirectional and multivariable Mendelian randomization (MR) analyses to estimate the effect of Vitamin D levels and validate the results, respectively.
- Meaning: MR is a statistical approach utilized to analyze causal relationships between exposure factors (i.e., genetic variants) and outcomes in epidemiological studies.
Gotcha. And now these findings.
A high serum level of 25(OH)D was found to be causally associated with an increased risk of wet AMD (odds ratio [OR] 1.35, 95% confidence interval [CI] 1.09-1.67, p = 0.005).
The causal effect of Vitamin D levels on the risk of wet AMD remained significant after adjusting for potential confounders in the multivariable MR analysis (OR 1.86, 95% CI 1.26-2.73, p = 0.002).
Otherwise: No causal effects were observed between other ocular diseases and Vitamin D concentrations in analyses.
Expert opinion?
Studies have shown that ultraviolet and blue light can lead to the damage of retinal pigment epithelium (RPE) cells.
Further, prior research has also demonstrated relationships between sunlight exposure and AMD, such as:
- Sunlight exposure during working life could increase the risk of early and late AMD.
- In Italy, individuals born in summer were reported to have a higher season-specific risk of neovascular AMD than those born in winter.
- An American study found a peak in 25(OH)D concentrations in August and a trough in February.
Meaning: “Since sunlight exposure is the main source of Vitamin D, we infer that additional sunlight exposure may increase the risk of (wet) AMD,” the study authors explained.
Limitations?
These included:
- Only European subjects were analyzed in this study, so these results may not extend to other populations and races
- The results of MR analysis were acquired via the genetic pathway—which may represent a limited view of Vitamin D’s biological pathways
- Limited demographic information from the GWAS data limited the ability to perform subgroup analyses
Take home.
These findings suggest a causal relationship between genetically predicted 25(OH)D (i.e., Vitamin D) levels and an increased risk of WAMD in European patients.
- However: The study authors remarked that this should be interpreted with caution due to potential confounding factors.