Rheopheresis for Age‐Related Macular Degeneration: A Novel Indication for Therapeutic Apheresis in Ophthalmology

Abstract

Age‐related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly. Successful therapy is not yet available for the majority of patients, especially not for patients with dry AMD. AMD at cellular and molecular levels is at least in part a microcirculatory disorder of the retina. Rheopheresis is a safe and effective modality of therapeutic apheresis to treat microcirculatory disorders and represents a novel treatment option for patients with dry AMD. Elimination of a defined spectrum of high molecular weight proteins from human plasma including pathophysiologically relevant risk factors for AMD such as fibrinogen, cholesterol, von Willebrand factor, and α2‐macroglobulin 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 a series of Rheopheresis treatments lead to rapid changes of blood flow, subsequently inducing sustained improvement of microcirculation and recovery of retinal function. Two controlled randomized clinical trials demonstrated the safety and efficacy of Rheopheresis for the treatment of AMD patients, especially for those with the dry form. Recently the interim analysis of the sham‐controlled, double blind, randomized multicenter Multicenter Investigation of Rheopheresis for AMD (MIRA‐I) trial confirmed these results. The framework of completed and still ongoing controlled clinical trials in combination with postcertification studies including the RheoNet registry represents a comprehensive quality management approach for this novel interdisciplinary therapy for AMD. The development and continuous update of guidelines for the precise indication of Rheopheresis for AMD follows the requirements of evidence‐based medicine.

Is the Efficacy of LDL Apheresis in Ischemic Optic Neuropathy Linked to a Reduction in Endothelial Activation Markers?

“…Another visual disturbance attributable, like NAION, to an association with various cardiovascular risk factors is age-related macular degeneration (AMD) [19] . Although the pathogenesis of AMD is still unknown, Friedman [20] has hypothesized a hemodynamic model to explain the sequence of pathogenic events.…”

“…Based on that, the efficacy of therapeutic apheresis has been assessed in this optic disease, too, using rheopheresis [19,21] . The rationale for this procedure is the fact that rheopheresis directly targets the elimination of known vascular risk factors and suspected pathophysiologically relevant factors of AMD by lowering plasma viscosity and eliminating fibrinogen, cholesterol, von Willebrand factor, ␣ 2 macroglobulin, IgM, immune complex and probably multimeric vitronectin [22] .…”

“…For these reasons, in our previous experience in the treatment of NAION [3,4] we used only three sessions of LDL apheresis, and the improvement in visual acuity was apparent already after the first session. Instead, in AMD, the treatment protocols involved 10 treatments over a period of 21 weeks [19] or 8 treatments over a period of 10 weeks [21] and improvements in the visual parameters were apparent only after several weeks.…”

Stress repair mechanism activity explains inflammation and apoptosis

“…It generates and disintegrates insoluble fibrin in accord with autonomic balance to simultaneously govern a capillary gate mechanism (see page 9) that regulates tissue perfusion, capillary hemostasis, and organ function and a turbulence mechanism (see page 10) that regulates turbulent viscosity in arterial blood flow [222,[229][230][231]. The capillary gate component explains why von Willebrand Factor, Factor VIII, insoluble fibrin, d-Dimer (Fibrin Split Products), blood viscosity, blood coagulability, blood pressure, cardiac output, heart rate, capillary hemostasis, tissue perfusion, tissue oxygenation, atherosclerosis, and organ function all fluctuate in accord with autonomic balance [15,222,[231][232][233][234][235][236][237][238][239][240][241][242][243][244][245][246]. Its acute hyperactivation causes infarction, pulmonary embolus, thrombophlebitis, and high altitude pulmonary edema (HAPE) [189,190,195,199,[247][248][249][250][251][252][253][254][255][256][257][258][259][260][261][262][263][264][265]…”

A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress

“…It generates and disintegrates insoluble fibrin in accord with autonomic balance to simultaneously govern a capillary gate mechanism (see page 7) that regulates tissue perfusion, capillary hemostasis, and organ function and a turbulence mechanism (see page 8) that regulates turbulent viscosity in arterial blood flow [198,[226][227][228]. The capillary gate component explains why von Willebrand Factor, Factor VIII, insoluble fibrin, d-Dimer (Fibrin Split Products), blood viscosity, blood coagulability, blood pressure, cardiac output, heart rate, capillary hemostasis, tissue perfusion, tissue oxygenation, atherosclerosis, and organ function all fluctuate in accord with autonomic balance [198,199,[228][229][230][231][232][233][234][235][236][237][238][239][240][241][242][243]. Its acute hyperactivation causes infarction, pulmonary embolus, thrombophlebitis, and high altitude pulmonary edema (HAPE) [41,.…”