Associations between diabetic retinopathy, mortality, disease, and mental health: an umbrella review of observational meta-analyses

Background Diabetic retinopathy is a complication of diabetes affecting the eyes and can lead to blindless if left untreated. Several significant risk factors have been reported for DR, of which several can be classified as some form of disease. Furthermore, several systematic reviews have reported associations between several types of mortality and DR. Numerous meta-analyses have pooled the data on these factors, however, a systematic evaluation of these meta-analytic relationships is lacking. In this study, therefore, we performed an umbrella review of systematic reviews of meta-analyses for mortality, diseases and DR, grading the credibility of evidence. Methods A comprehensive database search for observational meta-analyses was conducted from inception until 29/04/2022 against pre-published inclusion criteria. For each meta-analytic outcome, a random-effects meta-analysis was re-conducted, stratifying by study design (and type of DR where possible) of included studies. Several statistical variables, including publication bias, heterogeneity, excess significance bias, and prediction intervals were used to grade the credibility of significant evidence from I to IV, using the recommendations from the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Results Of the 1,834 initial results, 11 systematic reviews with meta-analyses were included covering 16 independent outcomes (total participants = 299,655; median participants per outcome: 7,266; median individual studies per outcome = 5). Overall, 10/16 outcomes (62.5%) yielded significant results, most of which were graded as ‘highly suggestive’ (Grade II) evidence. DR was associated with all-cause and cardio-vascular mortality, obstructive sleep apnoea, depression eating disorders, and several forms of cognitive impairment. Conclusions Results show highly suggestive evidence for associations between health outcomes and/or conditions and DR. Public health professionals and practitioners should note these findings when developing and/or reviewing public health polices.