Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis for extracorporeal hemorheotherapy, eliminating an exactly defined spectrum of high molecular weight proteins from human plasma (e.g.: fibrinogen, alpha-2-macroglobulin, low-density lipoprotein cholesterol, IgM). This results in the improvement of blood flow and microcirculation initiated by lowering blood and plasma viscosity, and erythrocyte aggregation. In this context, microcirculation stands not only for the patency of small blood vessels, but for the complete interactive network between plasma, blood cells, the vessel wall, and cellular and extracellular compartments of the surrounding tissue. Insufficient tissue oxygenation leads to tissue damage, e.g., a microcirculatory disorder develops, creating acute as well as chronic symptoms. Therefore, impaired microcirculation has a rheologic, functional, and structural dimension with respect to involved organs or tissues. Rheopheresis represents a specific therapeutic approach with an acute rheologic as well as chronic functional and structural effects, which was confirmed in pilot and controlled clinical studies for several organ systems. Data from 2 controlled clinical trials are available for the safe and effective treatment in patients with age-related macular degeneration.

Idiopathic sudden hearing loss (ISHL) has been suggested to precipitate as final common pathway of microcirculatory impairment of the inner ear associated with a variety of etiologies and characterized by a local hyperviscosity syndrome in cochlear vessels. Therefore, we investigated the effect of Rheopheresis, a method of therapeutic apheresis reducing plasma viscosity and improving microcirculation on hearing recovery. Patients were randomly assigned to receive two Rheopheresis treatments, or treatment according to current German guidelines consisting either of i.v. corticosteroids (methylprednisolon 250 mg for 3 days and subsequent oral dosing with tapering to zero) or i.v. hemodilution (500 mL 6% hydroxyethyl starch plus 600 mg pentoxifylline per day), each applied for 10 days. The primary outcome parameter was absolute recovery of hearing as measured by pure tone audiometry 10 days after the start of treatment. Secondary outcomes were recovery of hearing at day 42, the improvement of speech audiometry, tinnitus and feeling of pressure and the frequency of adverse events. In total, 240 patients with sudden hearing loss were enrolled from otorhinolaryngological departments at hospitals as well as out-patient clinics in Germany. Analysis was performed for the intention-to-treat as well as per protocol population. Mean absolute recovery of hearing on day 10 within the intention-to-treat population (ITT, n = 193) was 23.95 dB (SD 15.05) in the Rheopheresis group and 24.29 dB (SD 15.48) in the control group. Equal efficacy of Rheopheresis and tested standard treatments was demonstrated (P = 0.00056). Single Rheopheresis led to a higher recovery of hearing after 48 h in patients with high plasma viscosity (>1.8 mPas s; P = 0.029) or high total protein (>74 g/dL; P = 0.02). However, an overall good recovery of ISHL was observed with none of the tested therapies being superior regarding the primary outcome parameter. Improvement of health-related quality of life as documented by the SF36 was higher in the Rheopheresis group, exhibiting a significant difference for the physical summary scale at the final follow-up at day 42 (P = 0.006). In conclusion, Rheopheresis proved to be an effective treatment option within the ENT armamentarium for ISHL. Two Rheopheresis treatments within 3 days lasting for about 2 h each could be used to replace a 10-day infusion regimen, especially in patients who desire fast recovery from acute hearing loss. Also, this may be a second line treatment option for patients refractory to i.v. corticosteroids or hemodilution.

Rheopheresis is a specifically designed application of double filtration plasmapheresis, for extracorporeal treatment of microcirculatory disorders. Safety and efficacy of Rheopheresis for wound healing and skin oxygenation were investigated in patients with critical limb ischemia. Twelve patients of Fontaine stage III-IV were treated with a series of 10 Rheopheresis sessions over 17 weeks. Transcutaneous oxygen pressure (tcpO(2)) and ankle-brachial index (ABI) were repeatedly determined to monitor the effects of the Rheopheresis treatment series on microcirculation and skin blood flow. Laboratory parameters of blood rheology were measured in addition to safety parameters and course of the pain syndrome was documented. In four patients (baseline Fontaine stage III) Rheopheresis was associated with an improvement of Fontaine stage, a pronounced increase in tcpO(2) and complete regression of the rest pain. As an adjunct therapeutic option, Rheopheresis may preserve a functional lower extremity, delay amputation or reduce the extent of amputation.

The purpose of establishing the RheoNet registry was to evaluate the safety and efficacy of rheopheresis, a specific method of therapeutic apheresis used to treat microcirculatory disorders. Apheresis centers providing rheopheresis therapy and physicians caring for the underlying disease were asked to participate in the registry, and the registry data were analyzed for safety and tolerability. Age-related macular degeneration (AMD) was selected as a model disease to evaluate efficacy. The RheoNet registry was successfully established recording 7722 rheopheresis treatments of 1110 patients, including 833 AMD patients. The mean age of patients was 72 years. Adverse events (AE) were reported in 5.67% of treatments, but termination of the treatment session was only required in 0.48%. Transient hypotension was the most frequently reported AE. No age-related increase in AE was observed. Ophthalmological data of 428 eyes (of 279 treated patients) with dry AMD could be analyzed; 85 eyes of 55 untreated AMD patients served as the control. At 6.75 +/- 5.25 months post-baseline, 42% of the treated eyes had improved visual acuity. The proportion of eyes with a decline in visual acuity was 17%, compared to 40% in the untreated controls (P < 0.01). The RheoNet registry has been successfully established and data analysis revealed that rheopheresis is a safe outpatient treatment for microcirculatory disorders. Moreover, RheoNet currently provides the largest evaluation of the efficacy of rheopheresis for dry AMD. Registry analysis contributes to a safe and appropriate use of rheopheresis in clinical practice.

Treatments leading to accelerated recovery in combination with a minimal number of therapeutic interventions, for example, Rheopheresis, seemed to have a considerable effect on QoL. Because there is a dearth of evidence of efficacy for any treatment option in ISHL, QoL can provide additional information when choosing the most appropriate treatment option.