Insulin Use and Risk of Diabetic Macular Edema in Diabetes Mellitus: A Systemic Review and Meta-Analysis of Observational Studies

BACKGROUND Diabetes mellitus is a common and serious disorder. A search of the literature reveals no comprehensive quantitative assessment of the association between insulin use and incidence of diabetic macular edema. Therefore, we performed a meta-analysis of observational studies to evaluate the effect of insulin use on the risk of developing macular edema. MATERIAL/METHODS Comparative studies published until May 2014 were searched through a comprehensive search of the Medline, Embase, and the Cochrane Library electronic databases. A systematic review and quantitative analysis of comparative studies reporting the effect of insulin use on the incidence of macular edema was performed. All analyses were performed using the Review Manager (RevMan) v.5 (Nordic Cochrane Centre, Copenhagen, Denmark). RESULTS A total of 202 905 individuals were included in the present meta-analysis. In a random-effects meta-analysis, the use of insulin was found to be associated with increased risk of macular edema (RR, 3.416; 95% CI, 2.417-4.829; I2, 86.6%). Analysis that just included high-quality studies showed that insulin use increased the risk of macular edema (RR, 2.728; 95% CI, 1.881-3.955; I2=77.7%). In cohort studies (RR, 4.509; 95% CI, 3.100-6.559; I2, 77.7%) but not in case-control studies (RR, 1.455; 95% CI, 0.520 to 4.066; I2, 95.9%), increased incidence of macular edema was observed. CONCLUSIONS The results of this meta-analysis of observational studies demonstrate that insulin use is a risk factor for diabetic macular edema. However, available data are still sparse, and in-depth analyses of the assessed associations in the context of additional longitudinal studies are highly desirable to enable more precise estimates and a better understanding of the role of insulin use in incidence of diabetic macular edema.