Effect of calcium dobesilate on progression of early diabetic retinopathy: a randomised double-blind study.
Ribeiro Maria L,Seres Andras I,Carneiro Angela M,Stur Michael,Zourdani Alain,Caillon Patricia,Cunha-Vaz José G,
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
BACKGROUND:The study was carried out to confirm the effect of calcium dobesilate (CaD) compared to placebo (PLA) on the blood-retinal barrier (BRB) permeability in early diabetic retinopathy (DR). METHODS:Adults with type II diabetes and early diabetic retinopathy (below level 47 of ETDRS grading and PVPR between 20 and 50x10(-6)/ min, plasma-free fluorescein) were included in this double-blind placebo-controlled study. Treatment was 2 g daily for 24 months. The primary parameter, posterior vitreous penetration ratio (PVPR), was measured every 6 months by fluorophotometry. Secondary parameters were fundus photography, fluorescein angiography and safety assessments. Metabolic control was performed every 3 months. RESULTS:A total of 194 patients started the treatment (98 CaD, 96 PLA) and 137 completed the 24-month study (69 CaD, 68 PLA). Both treatment groups were comparable at baseline, with ETDRS level 10 in about 59% of patients. Mean PVPR change from baseline after 24 months was significantly (P=0.002) lower in the CaD group [-3.87 (SD 12.03)] than in the PLA group [+2.03 (SD 12.86)], corresponding to a 13.2% decrease in the CaD group and a 7.3% increase in the PLA group. PVPR evolution was also analysed by HbA1c classes (<7%, between 7 and 9%, > or =9%) and results confirmed the superiority of CaD independently of the diabetes control level. A highly significant difference [CaD: -3.38 (SD 13.44) versus PLA: +3.50 (SD 13.70)] was also obtained in a subgroup of patients without anti-hypertensive and/or lipid-lowering agents (P=0.002 at 24 months). A further analysis of the secondary parameters showed significant changes in favour of CaD in the evolution from baseline to the last visit of haemorrhages (P=0.029), DR level (P=0.0006) and microaneurysms (P=0.013). Regarding safety, only 2.5% (n=5 patients/ events) of all adverse events reported were assessed as possibly or probably related to the test drug, while all serious adverse events were reported as unlikely. There was no statistical difference between groups. CONCLUSION:Calcium dobesilate 2 g daily for 2 years shows a significantly better activity than placebo on prevention of BRB disruption, independently of diabetes control. Tolerance was very good.
10.1007/s00417-006-0318-2
Calcium dobesilate: pharmacological profile related to its use in diabetic retinopathy.
Berthet P,Farine J C,Barras J P
International journal of clinical practice
Calcium dobesilate (Doxium) is used in the treatment of diabetic retinopathy. Clinical studies show a slowdown of the progression of the disease after long-term oral treatment. The main action of the drug is related to a reduction of microvascular permeability as measured by different parameters and methods (vitreous fluorophotometry, retinal haemorrhages, skin capillary resistance, blood albumin leakage, blood viscosity) leading to improved visual acuity. The pharmacological activity may be explained in part by the antioxidant properties of calcium dobesilate and its action on endothelium through the synthesis of nitric oxide, increasing the endothelium-dependent relaxation. The antioxidant effect was demonstrated in different in vitro and in vivo models by decreasing the peritoneal permeability in rats induced by pro-oxidant substances. Moreover, vascular leakage was also decreased by calcium dobesilate in a reperfusion model in streptozotocin induced diabetic rats after ischaemia of the central artery of the retina. Doxium may also preserve vascular endothelial function by acting directly as antioxidant to protect lipids from peroxidation.
The effectiveness and safety of Chinese patent medicines plus calcium dobesilate for the treatment of diabetic retinopathy: A network meta-analysis.
Heliyon
Chinese patent medicines (CPMs) are commonly prescribed by clinicians in China as adjuvant therapy for diabetic retinopathy (DR). The study of network meta-analysis (NMA) aims to compare the effectiveness and safety of three CPMs plus calcium dobesilate (CD) for DR, and to explore optimal CPM for treatment of DR. . Bayesian network meta-analyses were designed to evaluate the safety and effectiveness of different CPMs for the treatment of DR. Systematic Review Registration CRD42022323996. A total of 23 eligible RCTs involving 1824 patients were enrolled. Compared with CD alone, Cmpound Danshen Dripping Pills (DS) + CD or Qiming Granule (QM) + CD considerably enhanced best corrected visual acuity (BCVA); DS + CD or Compound Xueshuantong Capsule (XST) + CD significantly reduced macular thickness; CPMs + CD significantly reduced the level of VEGF. In addition, DS + CD or XST + CD over QM + CD in reducing macular thickness. As for the adverse events, the differences across different CPMs were not statistically significant, and no statistically significant difference between the CPMs and CD. DS plus CD or QM plus CD may be better effective in improving BCVA; DS plus CD or XST plus CD may be better effective in reducing macular thickness; The combination therapy all may be better effective in reducing the level of VEGF. As for safety profile that CPMs plus CD did not increase the incidence of adverse events. The results of this study might support DS as a relatively prior adjuvant therapy option for patients with DR.
10.1016/j.heliyon.2024.e24533
Effect of calcium dobesilate on the blood-retinal barrier in early diabetic retinopathy.
Leite E B,Mota M C,de Abreu J R,Cunha-Vaz J G
International ophthalmology
The effect of calcium dobesilate on the alteration of the blood-retinal barrier was studied in 41 adult-onset, non-insulin dependent diabetic patients with minimal or no retinopathy, randomly assigned to receive either oral calcium dobesilate (1000 mg twice daily) or a placebo for 12 months. The posterior vitreous value and the penetration ratio, determined by vitreous fluorophotometry, reflected stabilisation of blood-retinal barrier permeability in the calcium dobesilate patients and deterioration of blood retinal barrier in those given placebo. During the relatively short period of the study, one year, no significant change in microaneurysm and capillary closure gradings was observed. No side effects were associated with calcium dobesilate.
10.1007/bf00154206
Treatment of blood hyperviscosity with calcium dobesilate in patients with diabetic retinopathy.
Benarroch I S,Brodsky M,Rubinstein A,Viggiano C,Salama E A
Ophthalmic research
This double-blind randomized trial was carried out on 37 patients with diabetic retinopathy and blood hyperviscosity. 19 patients received calcium dobesilate in capsules of 500 mg 3 times daily for 3 months and 18 patients took 3 placebo capsules daily during the same period. Calcium dobesilate was found to reduce whole-blood viscosity in a statistically significant manner which was accompanied by a diminution of the albumin/globulin ratio and a significant reduction of fibrinogen and cholesterol levels. A statistically significant diminution of capillary fragility was also observed in the calcium dobesilate-treated group. These results indicate that calcium dobesilate, by restoring the integrity of the microvessels, and by lowering blood viscosity, could act favorably on the evolution of diabetic retinopathy.
10.1159/000265364
Efficacy of calcium dobesilate in treating Chinese patients with mild-to-moderate non-proliferative diabetic retinopathy (CALM-DR): protocol for a single-blind, multicentre, 24-armed cluster-randomised, controlled trial.
Hu Hao,Liu Jiang,Wang Duolao,Qiu Shanhu,Yuan Yang,Wang Fenghua,Wen Liang,Song Qi,Sun Zi-Lin
BMJ open
INTRODUCTION:Calcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy (DR) due to its potential in protecting against retinal vascular damage. However, there is limited evidence exploring its efficacy in combating DR progression. This study is aimed at evaluating whether CaD could prevent DR progression into an advanced stage among Chinese patients with mild-to-moderate non-proliferative DR (NPDR). METHODS AND ANALYSIS:This study is a single-blind, multicentre, cluster-randomised, controlled superiority trial. A total of 1272 patients with mild-to-moderate NPDR will be enrolled and randomly assigned at a 1:1 ratio into the control group (conventional treatment group) and the intervention group (conventional treatment plus CaD (500 mg three times per day) for 12 months). Patients will be followed at 1, 3, 6 and 12 months after randomisation and receiving treatments, with the severity of DR assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. The primary endpoint is the progression of DR during follow-up, which is defined as an increase of two or more steps in the ETDRS scale. The secondary endpoints include the concomitant changes in visual acuity, presence, number, location and type of retinal lesions, and retinal blood vessel diameter as well as the arteriovenous ratio at different visits. ETHICS AND DISSEMINATION:Each local ethics committee (first Vote: Ethical Review Committees of Zhongda Hospital of Southeast University (2019ZDSYLL132-P01)) has approved the study. The results will be published in high impact peer-reviewed scientific journals aimed at the general reader. TRIAL REGISTRATION NUMBERS:NCT04283162.
10.1136/bmjopen-2020-045256
Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis.
Zhang XinYuan,Liu Wei,Wu ShanShan,Jin JingLong,Li WeiHong,Wang NingLi
Science China. Life sciences
Many randomized clinical controlled trials have confirmed the efficacy and safety of calcium dobesilate in treating diabetic retinopathy (DR). This systematic review critically evaluated the evidence that links calcium dobesilate to DR. In this fixed-effects meta-analysis, a total of 221 pertinent English-language articles published between January 1975 and October 2013 were identified. Systematic searches of PUBMED, Springer Link and the Cochrane Clinical Trials Database were conducted using the keywords "diabetic retinopathy" and "calcium dobesilate". The extracted information included the study design, inclusion and exclusion criteria, setting, sample size, participant mean age, treatment regime, mean change in best corrected visual acuity, laboratory parameters, capillary fragility, intraocular pressure and fundus manifestations based on the findings of fluorescent angiography. The summary statistics indicated that calcium dobesilate was significantly associated with improving retinal microaneurysms (RR: 0.62, 95%CI: 0.42-0.90, P=0.01), retinal hemorrhages (RR: 0.39, 95% CI: 0.17-0.88, P=0.02); exudates (RR: 0.31, 95% CI: 0.12-0.81, P=0.02), reduction of whole blood viscosity (MD: -0.57 CP, 95% CI: -0.75 to -0.38, P<0.001), plasma viscosity (MD: -0.36 CP, 95% CI: -0.63 to -0.09, P=0.01) and blood cholesterol (MD: -0.48 mg mL(-1), 95% CI: -0.64-0.33, P<0.00001). Intraocular pressure was also significantly reduced (MD: -5.59 mmHg, 95% CI: -6.69 to -4.50, P<0.00001). The results indicate that calcium dobesilate effectively treats DR at the systematic and local ocular levels.
10.1007/s11427-014-4792-1
Calcium dobesilate in the treatment of diabetic retinopathy.
Garay Ricardo P,Hannaert Patrick,Chiavaroli Carlo
Treatments in endocrinology
The incidence of diabetic retinopathy is still increasing in developed countries. Tight glycemic control and laser therapy reduce vision loss and blindness, but do not reverse existing ocular damage and only slow the progression of the disease. New pharmacologic agents that are currently under development and are specifically directed against clearly defined biochemical targets (i.e. aldose reductase inhibitors and protein kinase C-beta inhibitors) have failed to demonstrate significant efficacy in the treatment of diabetic retinopathy in clinical trials. In contrast, calcium dobesilate (2,5-dihydroxybenzenesulfonate), which was discovered more than 40 years ago and is registered for the treatment of diabetic retinopathy in more than 20 countries remains, to our knowledge, the only angioprotective agent that reduces the progression of this disease. An overall review of published studies involving calcium dobesilate (CLS 2210) depicts a rather 'non-specific' compound acting moderately, but significantly, on the various and complex disorders that contribute to diabetic retinopathy. Recent studies have shown that calcium dobesilate is a potent antioxidant, particularly against the highly damaging hydroxyl radical. In addition, it improves diabetic endothelial dysfunction, reduces apoptosis, and slows vascular cell proliferation.
10.2165/00024677-200504040-00003