Study Links Low Vitamin D Levels to Dry Eye

In a large, longitudinal analysis published in American Journal of Ophthalmology, researchers examined more than 11 million adults and identified a statistically significant association between vitamin D deficiency and increased dry eye disease risk. Deficient patients demonstrated higher cumulative incidence across multiple follow-up intervals, reinforcing biological links between vitamin D signaling and ocular surface inflammation and suggesting a potential role for targeted screening and supportive supplementation strategies. Photo: Scott G. Hauswirth, OD. Click image to enlarge. Dry eye disease (DED) is a widely common condition that manifests in various ways. Those suffering with symptoms have reduced quality of life, and current therapies are not consistently effective and carry side effects. In the search for new treatments, the potential of vitamin D—due to its anti-inflammatory and immune-modulating properties—has been explored, albeit with mixed results. To further clarify the strength or weakness of vitamin D in the pathogenesis of DED, researchers conducted a new large-scale, longitudinal, retrospective cohort study, the results of which were published last month in American Journal of Ophthalmology.  Data were collected from the TriNetX US Collaborative Network, and included adults aged 18 or older. After propensity score matching and excluding patients with a prior DED diagnosis, researchers separated them into two cohorts: patients with a vitamin D deficiency diagnosis (5.8 million) and controls with no prior vitamin D deficiency diagnosis (5.9 million). Their results were as follows:Vitamin D deficiency was associated with a 28.6% higher hazard ratio (HR) of developing dry eye compared with matched controls (HR, 1.286).DED developed in 3.3% of those with vitamin D deficiency compared to 2.7% of the controls.The cumulative incidence of DED was consistently higher in the vitamin D–deficient cohort across all follow-up times (e.g., five years: 3.58% vs. 2.89%; 10 years: 7.22% vs. 5.52%; and 20 years: 17.87% vs. 14.16%). These findings support a link between vitamin D deficiency and increased dry eye risk in the US population, the authors wrote in their study. “There is biological plausibility for a link between vitamin D deficiency and DED, because vitamin D is locally metabolized in ocular tissues and the vitamin D receptor (VDR), the nuclear receptor that mediates calcitriol’s gene-regulating, anti-inflammatory effects, is expressed in the eye,” they continued. “Experimental studies indicate that active vitamin D (calcitriol) can dampen hyperosmotic-stress–induced corneal epithelial inflammation and oxidative stress and reduce epithelial apoptosis via VDR-dependent pathways, supporting a role for vitamin D signaling in maintaining ocular surface inflammatory homeostasis.” Furthermore, they wrote, additional research suggests that micronutrient balance, including vitamin D status, “may influence ocular surface ecology and the ocular microbiome.”Potential limitations noted by the authors include reliance on ICD-10 codes for defining deficiency and dry eye, lack of serum vitamin D level data and potential residual confounding. “Furthermore, ICD-10 based coding does not allow us to further examine which aspect of DED (symptoms, stability or tear production) is most impacted by vitamin D deficiency.” The researchers also point out that social determinants of health are not captured in the TriNetX database.Given the scale of this study showing the association between vitamin D deficiency and risk of DED incidence, coupled with the widespread prevalence of vitamin D deficiency globally, the authors say early screening and intervention strategies may improve ocular surface health and prevent vision-related discomfort associated with dry eye, particularly in those at risk. “In combination with calcium, vitamin D supplementation has been shown to improve other aspects of health, such as increasing bone mineral density in older adults,” wrote the authors. “By analogy, in patients with DED who are at risk for deficiency, identifying and correcting low vitamin D levels may be a reasonable adjunct to standard DED therapies, while recognizing that supplementation should be guided by general medical indications rather than used as a stand-alone treatment for DED.”They concluded by noting that prospective, randomized controlled studies would be needed to confirm causality, define dose-response relationships and determine whether vitamin D supplementation “can meaningfully reduce DED incidence or severity, ultimately informing targeted strategies to preserve ocular comfort, visual function and quality of life.”Click here for the journal source. Shmushkevich SB, et al. Vitamin D deficiency and dry eye disease: A retrospective cohort study. Am J Ophthalmol. February 26, 2026. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.