Associations between vitamin D status and sight threatening and non-sight threatening diabetic retinopathy: a systematic review and meta-analysis

Background: Vitamin D levels have been shown to be associated with diabetic retinopathy, however to date, no review has examined the relationship between vitamin D and sight threatening diabetic retinopathy (STDR) and non-sight threatening diabetic retinopathy (NSTDR). The aim of this review, therefore, was to pool associations between vitamin D deficiency (25(OH)D < 20 ng/mL) and STDR/NSTDR. A further aim was to examine associations between circulating 25(OH)D levels and STDR/NSTDR.

Methods: A systematic review of major databases was undertaken for studies published from inception to 22/04/2022, using a pre-published protocol. Studies reporting prevalence of STDR or NSTDR versus a control group with diabetes and no DR or DME and either (a) vitamin D deficiency prevalence, or (b) circulating 25(OH)D levels, were included. A random effects meta-analysis was undertaken.

Results: Following screening, 12 studies (n = 9057) were included in the meta-analysis. STDR was significantly associated with vitamin D deficiency (OR = 1.80 95%CI 1.40-2.30; p = <0.001), whereas NSTDR was not (OR = 1.07 95%CI 0.90-1.27; p = 0.48). Both conclusions were graded as low credibility of evidence. Furthermore, circulating 25(OH)D levels were significantly associated with both NSTDR (SMD = -0.27 95%CI -0.50; -0.04; p = 0.02) and STDR (SMD = -0.49 95%CI -0.90; -0.07; p = 0.02), although these were graded as low credibility of evidence.

Conclusion: Vitamin D deficiency is significantly associated with STDR (including DME), but not with NSTDR. Given the well-reported associations between vitamin D deficiency and other unfavourable outcomes, it is important that vitamin D deficiency is managed appropriately and in a timely manner to reduce the risk of blindness in people with diabetes.