Effect of sulodexide in patients with non-proliferative diabetic retinopathy: diabetic retinopathy sulodexide study (DRESS)

Abstract

PurposeTo evaluate the effectiveness of sulodexide for the treatment of hard exudates (HE) in non-proliferative diabetic retinopathy (NPDR).MethodsThis was a randomized, placebo-controlled, multicenter trial involving 130 patients (65 for each group) who had mild-to-moderate NPDR with macular HE. Participants were given a daily dose of either 50 mg sulodexide or a matching dose of placebo orally for 12 months. Main outcome measure was an improvement in HE defined as a decrease in severity by at least two grades on a 10-grade severity scale. This was evaluated by fundus photography over 12-month period.ResultsThe sulodexide group showed significantly greater improvement in HE severity than that shown by the placebo group (39.0 % vs. 19.3 %; chi square, P = 0.005). Logistic regression analysis yielded an odds ratio of 2.790 (95 % confidence interval, 1.155-6.743; P = 0.023) for the effect of treatment once adjustments were made for demographic, prognostic and disease confounders. Intention to treat and per-protocol analysis yielded similar results. Sulodexide’s safety was comparable to that of the placebo.ConclusionsOral sulodexide therapy over 12 months improved macular HE in patients with mild-to-moderate NPDR, without leading to detectable adverse events. The study protocol was registered on clinicaltrial.gov under identifier NCT01295775.

Effect of grape seed proanthocyanidin extract on hard exudates in patients with non-proliferative diabetic retinopathy

“…Song et al (DRESS study group) conducted a clinical trial with a similar design to our study and suggested that oral sulodexide, which is a highly purified glycosaminoglycan (GAG), showed a significant decrease in HEs in patients with mild to moderate NPDR, with central foveal thickness ≤300 μm. [19] Based on previous animal study, [24] they presumed that oral sulodexide may repair endothelial damage due to diabetes and normalize the vascular permeability and GAG metabolism, resulting in resorption of HEs. They reported that oral sulodexide did not show significant differences in central retinal thickness compared to the placebo group.…”

“…[18] This grading system for HE severity has been used in a previously published clinical trial from our group. [19] We used this grading system without modification. Briefly, this grading system was based on the area of retina involved by HE and the amount of HE observed; the ETDRS standard photographs 3 and 4 were used for comparison.…”

A Clinical Experience on Sulodexide in the Treatment of Patients with Diabetic Nephropathy

“…Furthermore, sulodexide has other pharmacological effects potentially useful in the diabetic patients, subject to a high probability of developing acute cardiovascular diseases: anti-thrombotic activity, decrease of oxidative stress, hypolipidemic effect, prevention of glucose toxicity, suppression of cellular inflammation and anti-atheromatous effects [6]. Several clinical studies demonstrated sulodexide efficacy in patients, diabetic and not diabetic, affected by vascular diseases associated with a thrombotic risk: peripheral occlusive arterial diseases [29,30], prevention of recurrent deep venous thrombosis [31,32], diabetic retinopathy [33], diabetic foot [34,35], cerebrovascular [36,37] and cardiovascular diseases [38,39] and management of chronic venous disease, including the more severe and complicated cases such as venous ulcers [40][41][42].…”

New Therapeutic Approaches in Diabetic Retinopathy

“…A phase II randomized controlled trial evaluated the effects of oral therapy with a glycosaminoglycan (GAG), sulodexide (Vessel Due F, Aju Pharm, Seoul, South Korea, under license from Alfa Wassermann, Bologna, Italy), on hard exudates in patients with NPDR, and reported a significant reduction in these exudates compared with placebo [95]. The premise for this clinical trial was that in diabetic retinopathy, similar to diabetic nephropathy, GAGs are replaced by collagen in the retinal capillary basement membrane, leading to changes in the permeability of these capillaries [95,96].…”

“…The premise for this clinical trial was that in diabetic retinopathy, similar to diabetic nephropathy, GAGs are replaced by collagen in the retinal capillary basement membrane, leading to changes in the permeability of these capillaries [95,96]. Currently, the role of dietary supplements such as alpha-lipoic acid and multicomponent nutritional capsules in the management of NPDR are also being evaluated in a number of clinical trials [97,98].…”