To systematically review the effectiveness of systemic interventions for diabetic retinopathy (DR) in type 1 diabetes.

Systematic review and meta-analysis.

MEDLINE, EMBASE and Cochrane Library were searched for studies published from January 1990 to December 2014. Randomized controlled trials and controlled cohort studies reporting incidence or progression of DR following systemic intervention were included. Two reviewers selected studies, extracted data, and assessed risk of bias. For each intervention, pooled outcomes were reported as relative risk (RR) estimates with 95% confidence intervals (CI).

Twenty-four studies involving 9302 patients met inclusion criteria. Incident DR was reduced by intensive vs conventional insulin therapy (RR 0.43; 95% CI 0.23–0.83), insulin pumps vs multiple daily injections (RR 0.45; 95% CI 0.24–0.83), and angiotensin receptor blockade vs placebo (RR 0.65; 95% CI 0.49–0.85). The benefit of insulin pumps over multiple daily infections was independent of HbA1c. DR progression was reduced by intensive vs conventional insulin therapy (RR 0.63; 95% CI 0.43–0.92), angiotensin-converting enzyme inhibition vs placebo (RR 0.60; 95% CI 0.41–0.86), and islet cell transplantation vs medical therapy (RR 0.25; 95% CI 0.08–0.71).

Intensive insulin therapy, and specifically insulin pump therapy vs multiple daily injections, prevents DR in both adults and adolescents with type 1 diabetes. Antihypertensive agents provide protection in normotensive, normoalbuminuric adults. In patients with type 1 diabetes of longer duration, islet cell transplantation may be more effective than medical therapy. There is insufficient evidence for antilipid therapy or other systemic interventions.