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The Macula pp 149–170Cite as

Interim analysis of the MIRA-1 — multicenter double masked placebo controlled trial of rheopheresis in dry age-related macular degeneration (AMD) with soft drusen

Part of the Framework of Clinical Studies and Investigations to Prove Safety and Efficacy of Rheopheresis as a Novel Treatment Option for AMD

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Abstract

Rheopheresis is a safe and effective modality of therapeutic apheresis to treat microcirculatory disorders. Elimination of a defined spectrum of high molecular weight proteins from human plasma including pathophysiologically relevant risk factors for AMD such as fibrinogen, LDL-cholesterol, α2-macroglobulin, fibronectin, and von-Willebrand factor results in the reduction of blood and plasma viscosity as well as erythrocyte and thrombocyte aggregation. Pulses of lowering blood and plasma viscosity performed as series of Rheopheresis treatments lead to rapid changes of blood flow, with the potential induction of sustained improvement of microcirculation, and recovery of retinal function. Change of the activity of promotors of the natural course of AMD development and progression might represent the mechanism of sustained improvement of microcirculation, i.e. recovery of retinal function. To evaluate safety and efficacy of Rheopheresis for the treatment of dry AMD with soft drusen in the MIRA-1 trial 150 patients are to be randomized in a 2:1 ratio to receive 8 Rheopheresis or 8 sham apheresis treatments over 10 weeks and followed for one year. Investigational sites include 9 study centers and an additional reading center in the US. Qualified patients have dry AMD with multiple large soft drusen, VAC of 0.16–0.625, and for homogeneity of patient groups defined serum levels of selected high-molecular weight plasma proteins. The interim analysis included 43 subjects. In primary eyes the mean ETDRS-line difference at 12 months post baseline between treated and control group was 1.6 lines (p = 0.0011, repeated measures analysis). The difference was significant throughout the first post-treatment year. Subgroup analysis indicated that eyes with baseline VAC worse than 20/40 derived the greatest treatment benefit at one year with mean difference of 3.0 ETDRS-lines compared to placebo (p = 0.001). No severe treatment related adverse events occurred. In conclusion the interim analysis of the MIRA-1 trial demonstrated statistically significant and clinically relevant effects of Rheopheresis on VAC when compared to placebo controls for the 12-month study interval. The framework of completed and still ongoing controlled clinical trials in combination with post certification studies including the RheoNet-registry represents a comprehensive quality management approach for this novel interdisciplinary therapy for AMD. A hypothesis based upon current knowledge of pathogenic mechanisms of the development and progression of AMD can be conclusively linked with the putative mechanism of action of Rheopheresis for AMD. A recommendation for high-risk AMD-patients was defined. Based on the positive results of the MIRA-1 interim analysis 8 Rheopheresis treatments are currently recommended as the initial treatment series.

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Authors and Affiliations

  1. Apheresis Research Institute, Stadtwaldguertel 77, D50935, Cologne, Germany

    Reinhard Klingel MD, PhD

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  1. Reinhard Klingel MD, PhD
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Correspondence to Reinhard Klingel MD, PhD .

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  1. The Ludwig Boltzmann Institute of Retinology and Biomicroscopic Laser Surgery, Department of Ophthalmology, Rudolf Foundation Clinic, Vienna, Austria

    Susanne Binder

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Klingel, R. (2004). Interim analysis of the MIRA-1 — multicenter double masked placebo controlled trial of rheopheresis in dry age-related macular degeneration (AMD) with soft drusen. In: Binder, S. (eds) The Macula. Springer, Vienna. https://doi.org/10.1007/978-3-7091-7985-7_18

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  • DOI: https://doi.org/10.1007/978-3-7091-7985-7_18

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-7987-1

  • Online ISBN: 978-3-7091-7985-7

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