chondroitin-sulfates and Diabetic-Retinopathy

In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.

Topics: Adult; Aged; Analysis of Variance; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Double-Blind Method; Drug Combinations; Endothelium, Vascular; Exudates and Transudates; Female; Follow-Up Studies; Heparitin Sulfate; Humans; Kidney Function Tests; Male; Middle Aged; Proteinuria; Reference Values; Statistics, Nonparametric; von Willebrand Factor

In diabetes mellitus, both retinopathy and nephropathy represent specific microvascular disease with increased capillary permeability resulting in hard exudates, foveal oedema, and albuminuria. The decrease of heparan-sulphate content of the glomerular-basement membrane is quantitatively related to the rate of proteinuria in nephropathy associated with insulin-dependent diabetes mellitus (IDDM). Several short-term studies in patients with IDDM and non-IDDM have shown that a reduction of microalbuminuria and macroalbuminuria can be achieved with the supplementation of glycosaminoglycans. After completion of a study on the effect of danaparoid sodium on albumin excretion in patients with IDDM and macroalbuminuria, we hypothesised that treatment with danaparoid sodium also influenced retinal leakage in the patients in that trial.. In this retrospective study nine patients with nephropathy received 750 anti-Xa units danaparoid sodium once a day for 6 weeks in a placebo-controlled double-blind cross-over study. Fundus photographs, done at baseline and at the end of the study, were semiquantitatively scored for the severity of hard exudates.. At baseline 14 eyes had grade 1 to 5 severity of hard exudates and four eyes were without hard exudates (grade 0). There was no progression in the latter four eyes. In ten eyes an improvement was observed: four patients showed a favourable response to treatment in both eyes and two patients showed improvement in one eye. We found improvement of hard exudates after 6 weeks of treatment with danaparoid sodium.. Our uncontrolled observation indicates that the supplementation of danaparoid sodium influences both the permeability of retinal vessels as well as of glomerular vessels. Danaparoid-sodium therapy as a systemic adjuvant is worth considering for treatment strategies for foveal oedema and hard exudates in diabetic maculopathy.

Topics: Adult; Chondroitin Sulfates; Cross-Over Studies; Dermatan Sulfate; Diabetic Retinopathy; Double-Blind Method; Drug Combinations; Exudates and Transudates; Female; Heparitin Sulfate; Humans; Male; Retrospective Studies

To evaluate prospectively the efficacy and safety of posterior juxtascleral infusion of a new formulation of triamcinolone acetonide for refractory diffuse diabetic macular edema.. This was an interventional case series. Twenty-two consecutive eyes of 18 patients with refractory diffuse diabetic macular edema were included in the study. Each patient underwent a complete ophthalmic examination, including optical coherence tomography (OCT) and digital fluorescein angiography (FA). All patients received a suspension of 40 mg triamcinolone acetonide, 20 mg sodium chondroitin sulfate, and 15 mg sodium hyaluronate (1.5 mL), delivered posteriorly through a conjunctival and Tenon's incision. All patients completed the 1-year follow-up.. On average, studied eyes received 1.5 treatments. Mean preoperative foveal thickness (+/-SD) and visual acuity (+/-SD) were 474.2 +/- 136.6 microm and 0.6 +/- 0.37 logarithm of the minimum angle of resolution (logMAR), respectively. The central foveal thickness was significantly reduced from baseline at every follow-up visit (P < 0.001). Mean (+/-SD) reductions in macular thickness were 136 +/- 108 microm at 1 week and 128 +/- 122 microm after 1 year of follow-up. Mean (+/-SD) improvement in visual acuity at 12 months was 0.15 +/- 0.21 logMAR (P = 0.008). Visual acuity improvement of one or more lines and three or more lines were observed in 14 (63.6%) and 6 (27.3%) eyes, respectively. Seven eyes (31.8%) required topical treatment due to a significant intraocular pressure increase.. Posterior juxtascleral infusion of a new formulation of triamcinolone acetonide is an effective treatment for diffuse diabetic macular edema unresponsive to conventional grid laser photocoagulation. A randomized, larger study is warranted.

Topics: Aged; Chondroitin Sulfates; Diabetic Retinopathy; Drug Therapy, Combination; Female; Fluorescein Angiography; Follow-Up Studies; Glucocorticoids; Humans; Hyaluronic Acid; Infusions, Parenteral; Macular Edema; Male; Middle Aged; Prospective Studies; Sclera; Tomography, Optical Coherence; Treatment Outcome; Triamcinolone Acetonide; Visual Acuity

Topics: Chondroitin Sulfates; Dermatan Sulfate; Diabetic Retinopathy; Drug Combinations; Endothelial Growth Factors; Heparinoids; Heparitin Sulfate; Humans; Lymphokines; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors