Results from a large longitudinal study published in the American Journal of Ophthalmology suggest that low vitamin D levels may represent a modifiable risk factor in the development of ocular surface disease (OSD)—particularly dry eye disease (DED).
Let’s start with the basics of DED.
DED is a common ocular surface condition characterized by:
- Tear film instability
- Ocular surface inflammation
- Symptoms such as irritation, burning and fluctuating vision
Importantly: It can also significantly affect quality of life and remains challenging to manage in many patients—with systemic contributors such as nutrition and immune regulation playing an influential role in ocular surface health.
Give me some background on this…
Vitamin D has anti-inflammatory and immunomodulatory properties that may help regulate immune activity on the ocular surface.
- In fact: Researchers have increasingly explored whether Vitamin D status might influence the development or severity of DED.
Case in point: Experimental and clinical studies suggest that active Vitamin D metabolites may reduce corneal epithelial inflammation and oxidative stress while helping maintain ocular surface homeostasis.
- Still, findings across previous studies have been mixed, leaving uncertainty about how strongly Vitamin D deficiency contributes to the development of DED.
So where does this study fit in?
To better clarify this relationship, researchers conducted a large retrospective cohort study using data from the TriNetX U.S. Collaborative Network.
Investigators analyzed records from more than 11 million adults to evaluate whether individuals diagnosed with Vitamin D deficiency were more likely to develop DED over time.
Who was included in the study?
The analysis included adults aged 18 years or older, divided into two matched cohorts:
- 5.8 million patients diagnosed with vitamin D deficiency
- 5.9 million control patients without a prior Vitamin D deficiency diagnosis
After propensity score matching and excluding individuals with a previous DED diagnosis, researchers tracked the development of DED over multiple follow-up intervals.
So what did they find?
The most notable finding was that Vitamin D deficiency was associated with a significantly higher risk of developing DED.
Patients with Vitamin D deficiency had:
- A 28.6% higher hazard ratio (HR) of developing DED compared with matched controls
- A higher overall incidence of DED (3.3% vs. 2.7%)
And in the follow-up periods?
Cumulative incidence remained consistently higher in the Vitamin D–deficient group across all follow-up intervals:
- 5 years: 3.58% vs. 2.89%
- 10 years: 7.22% vs. 5.52%
- 20 years: 17.87% vs. 14.16%
These results reinforce a statistically significant association between Vitamin D deficiency and increased dry eye risk.
What biological factors might link Vitamin D deficiency to dry eye?
The study authors noted several biological mechanisms that could help explain this association.
- Vitamin D receptors are expressed in ocular tissues, and Vitamin D signaling plays a role in regulating inflammation and immune responses within the eye.
- Laboratory studies have shown that active Vitamin D metabolites can reduce hyperosmotic stress–induced inflammation in corneal epithelial cells and may limit oxidative damage and epithelial cell death.
Researchers have also suggested that micronutrient balance, including Vitamin D status, may influence the ocular surface environment and possibly the ocular microbiome.
Any limitations to consider when interpreting the data?
As with many large database studies, several limitations should be considered.
- The study relied on International Classification of Diseases (ICD)-10 diagnostic codes to identify both Vitamin D deficiency and DED.
- Researchers did not have access to actual serum Vitamin D levels, which limited the ability to examine dose-response relationships.
- Residual confounding factors may still exist despite propensity score matching.
In addition, social determinants of health were not captured in the TriNetX database.
What do the findings suggest about screening or patient care?
Given the large population analyzed and the consistent association observed, the authors suggested that screening for Vitamin D deficiency may be worth considering in patients at risk for DED.
Identifying and correcting low vitamin D levels could potentially serve as an adjunct to conventional dry eye treatments, particularly in patients with known deficiency.
Why does this matter clinically?
As DED remains highly prevalent and difficult to manage in some patients, identifying systemic risk factors that contribute to ocular surface inflammation could help clinicians adopt a more comprehensive approach to treatment.
And because Vitamin D deficiency is common worldwide, recognizing its potential association with DED may provide another avenue for improving ocular surface health.
Any final thoughts?
While these findings do not prove causation, they highlight a possible link between Vitamin D status and ocular surface inflammation, suggesting that screening and correcting deficiency may support broader dry eye management strategies.