Advertisement

Prospective, randomized, controlled clinical study evaluating the efficacy of Rheopheresis for dry age-related macular degeneration

Dry AMD treatment with Rheopheresis Trial–ART
  • Michael Janusz Koss
  • Peter Kurz
  • Theoharis Tsobanelis
  • Walter Lehmacher
  • Cordula Fassbender
  • Reinhard Klingel
  • Frank H. J. Koch
Retinal Disorders

Abstract

Purpose

To evaluate Rheopheresis for the treatment of patients with high-risk dry age-related macular degeneration and no therapeutic alternative. Rheopheresis is a method of therapeutic apheresis using the methodology of double filtration plasmapheresis to treat microcirculatory disorders.

Methods

The dry AMD treatment with Rheopheresis trial (ART) was a randomised, controlled clinical study. Patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen (the fellow eye had advanced AMD) were randomly assigned in a 1:1 ratio to receive ten Rheopheresis treatments within 17 weeks or to remain untreated. The primary outcome was change in best-corrected ETDRS-visual acuity (mean logMar change) after 7.5 months compared to baseline visual acuity for both groups.

Results

Forty-three eyes of 43 patients (22 treatment and 21 control group) were analysed. The mean baseline BCVA in study eyes was 0.58 in the treatment group and 0.66 in the control group (n.s. p = 0.19). At the primary efficacy endpoint 7.5 months post baseline, there was a statistically significant mean difference of 0.95 ETDRS lines (p = 0.01) between the Rheopheresis and control groups. Nine percent of eyes in the group treated with Rheopheresis gained 2 or more ETDRS lines, as compared with 0% of eyes with no treatment. None of the treated patients had a loss in visual acuity in their study eyes, as compared with 24% of patients without treatment who lost 1 ETDRS line or more; 19% lost 2 ETDRS lines or more. Rheopheresis treatment was safe and well-tolerated.

Conclusion

The results of ART provide further evidence that Rheopheresis is a safe and effective therapeutic option for high-risk patients with dry AMD and no therapeutic alternative. A series of Rheopheresis treatments can improve the natural course of AMD for selected patients.

Keywords

Dry AMD Macular degeneration Rheopheresis Apheresis Microcirculation 

Notes

Acknowledgements

We thank the following experts for their advice and comments: Prof. Brunner, Prof. Engelmann, Prof. Kirchhof, Prof. Koch, Prof. Nasemann, Prof. Schölzel-Klatt, Prof. Walter.

References

  1. 1.
    Klaver CCW, Assink JJM, van Leeuwen R, Wolf RCW, Vingerling JR, Stijnen T, Hofman A, de Jong PTV (2001) Incidence and progression rates of age- related maculopathy: the Rotterdam study. Invest Ophthalmol Vis Sci 42:2237–2241PubMedGoogle Scholar
  2. 2.
    Trautner C, Haastert B, Richter B, Berger M, Giani G (2003) Incidence of blindness in southern Germany due to glaucoma and degenerative conditions. Invest Ophthalmol Vis Sci 44:1031–1034PubMedCrossRefGoogle Scholar
  3. 3.
    Owen CG, Fletcher AE, Donohgue M, Rudnicka AR (2006) How big is the burden of visual loss caused by age related macular degeneration in the United Kingdom. Br J Ophthalmol 87:312–317CrossRefGoogle Scholar
  4. 4.
    Jager RD, Mieler WF, Miller JW (2008) Age-related macular degeneration. N Engl J Med 358:2606–2617PubMedCrossRefGoogle Scholar
  5. 5.
    Age-Related Eye Disease Study Research Group (2001) A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no.8. Arch Ophthalmol 119(10):1533–1534Google Scholar
  6. 6.
    Pulido JS, MIRA-1 study group (2002) Multicener prospective, randomized, double-masked, placebo-controlled study of rheopheresis to treat nonexdudative age-related macular degeneration: Interim analysis. Trans Am Ophthalmol Soc 100:85–108PubMedGoogle Scholar
  7. 7.
    Klein R, Peto T, Bird A, Vannewkirk MR (2004) The epidemiology of age-related macular degeneration. Arch Ophthalmol 122:564–572CrossRefGoogle Scholar
  8. 8.
    Moshfeghi DM, Blumenkranz MS (2007) Role of genetic factors and inflammation in age-related macular degeneration. Retina 27(3):269–275PubMedCrossRefGoogle Scholar
  9. 9.
    Pulido JS, Sanders D, Klingel R (2005) Rheopheresis for age-related macular degeneration: clinical results and putative mechanism of action. Can J Ophthalmol 40:332–340PubMedGoogle Scholar
  10. 10.
    Klingel R, Ch M, Fassbender T, Himmelsbach F, Altes U, Lotz J, Pohlmann T, Beyer J, Küstner E (2003) Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open-label prospective pilot trial. Ther Aper Dial 7(4):444–455CrossRefGoogle Scholar
  11. 11.
    Klingel R, Erdtracht B, Gauss V, Piazolo A, Mausfeld-Lafdhiya P, Diehm C (2005) Rheopheresis in patients with critical limb ischemia—results of an open-label prospective pilot trial. Ther Apher Dial 9(6):473–481PubMedCrossRefGoogle Scholar
  12. 12.
    Lüke C, Widder RA, Soudavar F, Walter P, Brunner R, Borberg H (2001) Improvement of macular function by membrane differential filtration in diabetic retinopathy. J Clin Apher 16:23–28PubMedCrossRefGoogle Scholar
  13. 13.
    Mösges R, Köberlein J, Heibges A, Erdtracht B, Klingel R, Lehmacher W for the RHEO-ISHL study group (2008) Rheopheresis for idiopathic sudden hearing loss: results from a large prospective, multicenter, randomized, controlled clinical trial. Eur Arch Otorhinolaryngol Oct 16 [Epub ahead of print]; doi: 10.1007/s00405-008-0823-5
  14. 14.
    Brunner R, Widder RA, Walter P, Lüke C, Godehardt E, Bartz-Schmidt K-U, Heimann K, Borberg H (2000) Influence of membrane differential filtration on the natural course of age-related macular degeneration, a randomized trial. Retina 20:483–491PubMedCrossRefGoogle Scholar
  15. 15.
    Widder RA, Farvili E, Reis RGJ, Lüke C, Walter P, Kirchhof B, Borberg H, Brunner R (2002) The treatment of age-related macular degeneration (ARMD) with extracorporeal treatment procedures; a follow-up of four years. Invest Ophthalmol Vis Sci 43: 2906 [ARVO Meeting E-Abstract]Google Scholar
  16. 16.
    Swartz M, Rabetoy G (1999) Treatment of non-exudative age-related macular degeneration using membrane differential filtration apheresis (abstract). Invest Ophthalmol Vis Sci 40:319Google Scholar
  17. 17.
    Boyer D, MIRA-1 study group (2006) Rheopheresis for dry AMD—efficacy and safety analysis of the pivotal MIRA-1 clinical trial. Invest Ophthalmol Vis Sci 47:2176 [ARVO Meeting E-Abstract]Google Scholar
  18. 18.
    Pulido JS, Winters JL, Boyer D (2006) Preliminary analysis of the final multicenter investigation of Rheopheresis for age-related macular degeneration (AMD) trial (MIRA-1) results. Trans Am Opthalmol Soc 104:221–231Google Scholar
  19. 19.
    Klingel R, Fassbender C, Fassbender T, Erdtracht B, Berrouschot J (2000) Rheopheresis: rheologic, functional and structural aspects. Ther Apher 4(5):348–357PubMedCrossRefGoogle Scholar
  20. 20.
    Heibges A, Fassbender C, Erdtracht B, Koch F, Klingel R (2007) Assessment of safety and efficacy of Rheopheresis for dry age-related macular degeneration (AMD) by RheoNet-registry analysis. Nephro-News September 2007:30 (abstract) Google Scholar
  21. 21.
    Wong T, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, Fahrbach K, Probst C, Sledge I (2008) The natural history and prognosis of neovascular age-related macular degeneration: a systemic review of the literature and meta-analysis. Ophthalmology 115(1):116–126PubMedCrossRefGoogle Scholar
  22. 22.
    Braun O, Vinding T, Krogh E (1993) Natural course in fellow eyes of patients with unilateral age-related exudative maculopathy. A fluorescein angiographic 4- year follow up of 45 patients. Acta Ophthalmol (Copenh) 71(3):398–401CrossRefGoogle Scholar
  23. 23.
    Klein R et al (1997) The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 104:7–21PubMedGoogle Scholar
  24. 24.
    Grunwald JE, Harisprasad S, DuPont JC (1998) Effect of aging on foveolar choroidal circulation. Arch Ophthalmol 116:150–154PubMedGoogle Scholar
  25. 25.
    Grunwald JE, Hariprasad S, DuPont JC (1998) Foveolar choroidal blood flow in age-related macular degeneration. Invest Ophthalmol Vis Sci 39:385–390PubMedGoogle Scholar
  26. 26.
    Grunwald JE, Metelitsina TI, Dupont JC, Ying GS, Maguire MG (2005) Reduced foveolar choroidal blood flow in eyes with increasing AMD severity. Invest Ophthalmol Vis Sci 46(3):1033–1038PubMedCrossRefGoogle Scholar
  27. 27.
    Brunner R, Widder RA, Fischer RA, Walter P, Bartz-Schmidt K-U, Heimann K (1996) Clinical efficacy of haemorheological treatment using plasma exchange, slective adsorption and membrane differential filtration in maculopathy, retinal vein occulosion and uveal effucsion syndrome. Transfus Sci 17:493–498PubMedGoogle Scholar
  28. 28.
    Soudavar F, Widder RA, Brunner R, Walter P, Barzt-Schmidt KU, Borberg H, Heimann K (1998) Changes of retinal haemodynamics after elimination of high molecular weight proteins and lipids in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci 39:386 [abstract]Google Scholar
  29. 29.
    Brody BL, Gamst AC, Williams RA, Smith AR, Lau PW, Dolnak D et al (2001) Depression, visual acuity, comorbiditiy and disability associated with age-related macular degeneration. Ophthalmol 108(10):1893–1901CrossRefGoogle Scholar
  30. 30.
    Fell AJ, Engelmann K, Richard G, Fassbender C, Wahls W, Klingel R (2002) Rheopherese—ein systemischer Therapieansatz für die altersabhängige Makuladegeneration (AMD)? Ophthalmologe 99:780–784PubMedCrossRefGoogle Scholar
  31. 31.
    Moesges R, Köberlein J, Erdtracht, Klingel R (2008) Quality of life in patients with idiopathic sudden hearing loss (ISHL): comparison of different therapies using the SF-36 questionnaire. Otol and Neurotol 29:769–775CrossRefGoogle Scholar
  32. 32.
    Hazel CA, Petre KL, Armstrong RA, Benson MT, Frost NA (2000) Visual function and subjective quality of life compared in subjects with acquired macular disease. Invest Ophthalmol Vis Sci 41(6):1309–1315PubMedGoogle Scholar
  33. 33.
    Wild C, Mathis B, Garthlehner G (2009) Rheopheresis for age-related macular degeneration. Ophthalmologe 106:127–132PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Michael Janusz Koss
    • 1
  • Peter Kurz
    • 2
  • Theoharis Tsobanelis
    • 2
  • Walter Lehmacher
    • 3
  • Cordula Fassbender
    • 4
  • Reinhard Klingel
    • 4
  • Frank H. J. Koch
    • 1
  1. 1.Department of OphthalmologyUniversity of FrankfurtFrankfurt/MainGermany
  2. 2.Center for Nephrology, Dialysis and ApheresisFrankfurtGermany
  3. 3.Institute for Medical Statistics, Informatics and EpidemiologyUniversity of CologneCologneGermany
  4. 4.Apheresis Research InstituteCologneGermany

Personalised recommendations