Vitamin D Deficiency Linked to Increased Risk of Noninfectious Uveitis

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A systematic review and meta-analysis provides insight into the potential for increased risk of noninfectious uveitis among people with vitamin D deficiency.

Vitamin D supplementation could help in the prevention of noninfectious uveitis, according to the findings of a recent study.

A systematic review and meta-analysis of studies examining associations between vitamin D deficiency and risk of noninfectious uveitis, results indicate patients considered vitamin D deficient had a risk of noninfectious uveitis more than twice that of their counterparts without vitamin D deficiency.

“Vitamin D supplementation could represent a possible therapeutic strategy for preventing or managing [noninfectious uveitis] if substantiated,” wrote investigators. “Clinicians should consider screening for and addressing vitamin D deficiency in patients with or at risk for [noninfectious uveitis].”

Few topics have been as extensively discussed or researched as the effects of vitamin D use and vitamin D deficiency. Characterized by its ability to suppress inflammation and influence the immune response, previous data has suggested vitamin D deficiency could be associated with increased risk of different ocular diseases.

With an interest in further exploring associations a team led by William Rojas-Carabali, MD, of Nanyang Technological University, a team of investigators launched and designed the current research endeavor as a systematic review and meta-analysis of data from studies within the Embase, PubMed, and Lilacs databases. Initially performed on January 25, 2022 and updated on May 8, 2023, the search returned more than 900 articles for screening.

For inclusion, articles needed to report patients with noninfectious uveitis and measurement of vitamin D levels. In total, investigators identified 933 for screening. From the 933 articles identified for screening, 11 were included in the systematic review and 5 were meta-analyzed. Among the 11 identified for inclusion, 6 were case-control studies, 2 were cohort studies, and 3 were cross-sectional studies.

The 5 studies included for meta-analysis 6082 individuals with noninfectious uveitis. Overall, investigators obtained data related to 354 cases and 5728 control patients.

Upon analysis, results indicated patients with noninfectious uveitis had significant lower 25(OH)D levels in serum compared with controls (SMD, -0.39; 95% Confidence Interval [CI], -0.71 to -0.08; P =.0007). However, investigators called attention to substantial heterogeneity among the studies (I2=79%). In sensitivity analyses, results pointed analyses showed changes in results when omitting each study (range, -0.53 to -0.28).

When only examining studies that measured vitamin D levels at any time before the onset of uveitis, results indicated those who developed uveitis had significant reduced levels of vitamin D relative to the control group (SMD, -0.37; 95% CI, -0.56 to -0.17). Investigators noted similar findings were observed when limiting their analysis to studies that only measured vitamin D levels 1 year before uveitis (SMD, -0.67; 95% CI,

-0.93 to-0.41; I2=0%). In a meta-analysis of studies reporting odds ratios [ORs], results demonstrated patients with noninfectious uveitis had a greater likelihood low vitamin D levels 1 year before disease onset (OR, 2.04; 95% CI, 1.55 to 2.68; P=.00001).

Investigators noted multiple limitations within their study for clinicians to consider. These included, but were not limited to, reliance on observational data, a relatively small sample size, and inherent heterogeneity in data.

“Our results show that patients with hypovitaminosis D are 2.04 times more likely to develop [noninfectious uveitis] than subjects with vitamin D sufficiency,” investigators added. “However, these conclusions are based on limited data from a few studies, suggesting that further research in this field is necessary. In future investigations, authors should standardize the measurement technique and cut-off values of serum vitamin D to reduce heterogeneity in meta-analysis.”


Rojas-Carabali W, Pineda-Sierra JS, Cifuentes-González C, et al. Vitamin D deficiency and non-infectious uveitis: A systematic review and Meta-analysis. Autoimmun Rev. Published online December 3, 2023. doi:10.1016/j.autrev.2023.103497

Pillar S, Amer R. The association between vitamin D and uveitis: A comprehensive review. Surv Ophthalmol. 2022;67(2):321-330. doi:10.1016/j.survophthal.2021.07.006