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Effect of calcium dobesilate on progression of early diabetic retinopathy: a randomised double-blind study

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Abstract

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 50×10−6/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%, ≥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.

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Acknowledgements

The authors would like to thank the statistician, Giancesare Gamba, PhD (Biometrix SA, CH-1196 Gland) and the other members of the DX-Retinopathy Study group: Austria – N. Maar, M. Tittl (Vienna); France – G. Coscas, G. Soubrane, L. Perlemuter, Z. Kahal, H. Oubraham (Créteil); Germany – C. Ohrloff (Frankfurt); Hungary – I. Süveges, A. Borbandy (Budapest); Portugal – E. Leite, C. Lobo (Coimbra) and JF. Castro-Correia, F. Falcão-dos-Reis (Porto); Switzerland – P. Leuenberger, A. Dosso, A. Golay, F. Ustun, L. Sekkat, M. Bagnoud (Geneva) and E. Messmer (Zürich).

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Authors and Affiliations

  1. AIBILI, Clinical Trial Centre, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal

    Maria L. Ribeiro & José G. Cunha-Vaz

  2. Department of Ophthalmology, Semmelweis University, 1083, Budapest, Hungary

    Andras I. Seres

  3. Department of Ophthalmology, Hospital de São João, 4200, Porto, Portugal

    Angela M. Carneiro

  4. Department of Ophthalmology, Medical University of Vienna, 1090, Vienna, Austria

    Michael Stur

  5. Department of Ophthalmology, University-Paris XII-Creteil, 94010, Creteil, France

    Alain Zourdani

  6. OM PHARMA, Rue du Bois-du-Lan 22, 1217, Meyrin/Geneva, Switzerland

    Patricia Caillon

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  1. Maria L. Ribeiro
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on behalf of the DX-Retinopathy Study Group

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Correspondence to Maria L. Ribeiro.

Additional information

The study was supported by a grant from OM PHARMA, Meyrin/Geneva, Switzerland. There are no financial interest and no conflict of interest for M.L. Ribeiro, the authors and the members of the study group. P. Caillon is the Clinical Project Manager of the study at OM PHARMA.

The authors have full control of all primary data and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data if requested.

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Ribeiro, M.L., Seres, A.I., Carneiro, A.M. et al. Effect of calcium dobesilate on progression of early diabetic retinopathy: a randomised double-blind study. Graefe's Arch Clin Exp Ophthalmol 244, 1591–1600 (2006). https://doi.org/10.1007/s00417-006-0318-2

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  • DOI: https://doi.org/10.1007/s00417-006-0318-2

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