Calcium dobesilate did not reduce risk for progression to clinically significant macular edema

Patients with type 2 diabetes and mild-to-moderate nonproliferative diabetic retinopathy assigned to calcium dobesilate were 32% more likely to develop clinically significant macular edema than patients assigned placebo, according to findings from the CALDIRET study.

Researchers compared the effect of calcium dobesilate with placebo on prolonging progression to clinically significant macular edema that required laser treatment in at least one eye. Researchers randomly assigned 635 adults to 1,500 mg calcium dobesilate per day or placebo.

“Our findings showed that calcium dobesilate could neither prevent occurrence of clinically significant macular edema nor reduce probability of developing clinically significant macular edema,” the researchers wrote.

After five years of follow-up, 86 of 324 patients assigned to calcium dobesilate developed clinically significant macular edema compared with 69 of 311 patients assigned to placebo.

The estimated five-year probability of developing clinically significant macular edema was 35% for the calcium dobesilate group and 28% for the placebo group (HR=1.32).

HbA1c was the “only baseline covariate providing significant predictive capacity for clinically significant macular edema development (OR=1.19),” the researchers wrote.

Cardiovascular and vision disorders were the most commonly reported adverse events, and rates were similar between groups (calcium dobesilate, 24%; placebo, 29%). During follow-up, nine patients (3%) in the calcium dobesilate group died compared with eight (3%) in the placebo group.

Post-hoc analyses revealed that “women with risk factors for vascular disease might benefit from treatment with calcium dobesilate, although this interpretation remains speculative,” the researchers wrote.

Calcium dobesilate use was encouraged in the late 1980s after studies demonstrated beneficial effects of the drug in patients with peripheral and cerebral diseases, diabetes, diabetic retinopathy and glaucoma.

In an accompanying editorial in The Lancet, Anna B. Einarsdóttir and Einar Stefánsson, MD, PhD, professor of ophthalmology, both at The University of Iceland in Reykjavik, emphasized that blindness due to diabetes can be prevented or reduced without reducing retinopathy.

“Systematic screening for diabetic retinopathy and preventive laser treatment for those who develop macular edema or proliferative retinopathy reduces the rate of blindness to about 0.5% in the diabetic population regardless of the prevalence of retinopathy,” they wrote.

Einarsdottir A. Lancet. 2009;373:1316-1318.

Haritoglou C. Lancet. 2009;373:1364-1371.