Effect of calcium dobesilate on occurrence of diabetic macular oedema (CALDIRET study): randomised, double-blind, placebo-controlled, multicentre trial.

BACKGROUND Medical treatment for diabetic retinopathy could have an important role in prevention of complications such as visual loss. We aimed to assess the effect of calcium dobesilate on occurrence of diabetic macular oedema. METHODS We undertook a randomised, double-blind, placebo-controlled, multicentre study in 40 centres in 11 countries. We enrolled outpatients with adult-onset type 2 diabetes and mild-to-moderate non-proliferative diabetic retinopathy, and randomly allocated them via sealed envelopes either calcium dobesilate (1500 mg per day) or placebo. The primary endpoint was development of clinically significant macular oedema (CSME) within a follow-up period of 5 years. Patients who dropped out of the study early were censored. Analysis was by intention to treat. FINDINGS We enrolled 635 patients. 324 were randomly allocated calcium dobesilate and 311 were assigned placebo. In the calcium dobesilate group, 86 patients developed CSME compared with 69 in the placebo group. Accounting for censored cases, estimated cumulative 5-year CSME probability was 35% and 28%, respectively (hazard ratio 1.32, 95% CI 0.96-1.81; p=0.0844). Adverse events did not differ between treatment groups (78 [24%] on calcium dobesilate and 90 [29%] with placebo). No relevant drug-related complications were noted. Nine patients (3%) died in the calcium dobesilate group and eight (3%) deaths were recorded on placebo. INTERPRETATION Calcium dobesilate did not reduce the risk of development of CSME.