Associations between diabetic retinopathy and modifiable risk factors: An umbrella review of meta-analyses

Aims: Several modifiable risk factors have been meta-analysed for diabetic retinopathy (DR), such as physical activity and vitamin D status. To date, these factors have not been systematically aggregated and the credibility of evidence assessed. Therefore, the aim of this umbrella review was to aggregate all modifiable risks of DR and assess the credibility of the evidence. Methods: An umbrella review of meta-analyses was undertaken. For each meta-analytic association, random-effects effect size, 95% confidence intervals (CIs), heterogeneity, small-study effects, excess significance bias and 95% prediction intervals were calculated. The credibility of significant evidence (p < 0.05) was graded from I to IV, using pre-defined criteria. Results: After initial searches, 13 studies were included covering 34 independent outcomes (total participants = 824,372). Positive associations were found between insulin usage and diabetic macular oedema (RR = 4.5; 95% CI 3.1–6.6), and DR risk (RR = 2.3; 95% CI 1.4–3.9) in people with type 2 diabetes. Vitamin D deficiency was associated with DR risk (OR = 2.8; 95% CI 1.1–7.1), as was obesity (RR = 1.34; 95% CI 1.06–1.68) and sedentary behaviour (RR = 1.22; 95%CI 1.03–1.44). Intensive blood pressure targets (RR = 0.8 95%CI 0.8–1.0), and moderate physical activity (RR = 0.69; 95%CI 0.53–0.91) yielded significant protective associations with DR. Conclusions: People with type 2 diabetes on insulin have a high risk of macular oedema and DR. Vitamin D deficiency yielded almost three times greater odds of DR, while intensive blood pressure control reduces DR risk by 20% and moderate physical activity by 31%. Healthcare professionals should use this evidence to identify those people most at risk to ensure that proper treatment and healthy lifestyles are recommended.