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. 2002;100:85–107.

Multicenter prospective, randomized, double-masked, placebo-controlled study of Rheopheresis to treat nonexudative age-related macular degeneration: interim analysis.

Jose S Pulido 1; Multicenter Investigation of Rheopheresis for AMD (MIRA-1) Study Group1
PMCID: PMC1358951  PMID: 12545682

Abstract

OBJECTIVE: To evaluate the safety and efficacy of Rheopheresis blood filtration to treat intermediate- to late-stage preangiogenic age-related macular degeneration (AMD) with soft drusen. DESIGN: Multicenter, prospective, randomized, double-masked, placebo-controlled clinical trial. PARTICIPANTS: First 43 randomized patients (28 Rheopheresis and 15 placebo-control patients) with available baseline and 3-month postbaseline best corrected visual acuity (BCVA) measurements and intermediate- to late-stage preangiogenic AMD with multiple large soft drusen and elevated serum levels of targeted macromolecules. INTERVENTION: Patients were randomly assigned to receive eight Rheopheresis or eight placebo procedures over 10 weeks. MAIN OUTCOME MEASURES: ETDRS BCVA measurements at baseline, 3, 6, 9, and 12 months postbaseline. RESULTS: In primary eyes, the mean LogMAR line difference between Rheopheresis and placebo-control eyes was 1.6 lines at 12 months postbaseline; the difference was significant throughout the first posttreatment year (P = .0011, repeated measures analysis). Thirteen percent of Rheopheresis compared with 0% of placebo-control eyes had a > or = 3-line improvement in BCVA at 12 months postbaseline. Four percent of Rheopheresis compared with 18% of placebo-control eyes had a > or = 3-line loss in BCVA. The subgroup of patients whose primary eyes had baseline BCVA worse than 20/40 demonstrated a mean LogMAR difference between Rheopheresis and placebo-control eyes equaling 3.0 lines at 12 months postbaseline; the difference was significant throughout the first posttreatment year (P = .0014, repeated measures analysis). Sixteen percent of Rheopheresis compared with 0% of the placebo-control eyes had a > or = 3-line improvement in BCVA at 12 months postbaseline. Five percent of Rheopheresis compared with 29% of placebo-control eyes had a > or = 3-line loss in BCVA. Fifty-eight percent of Rheopheresis eyes improved to 20/40 or better, compared with 14% of placebo-control eyes. No serious treatment-related adverse events were observed. CONCLUSIONS: Rheopheresis demonstrated statistically significant and clinically relevant effects on BCVA when compared with placebo controls for the 12-month study interval. Untreated patients with BCVA worse than 20/40 with intermediate- to late-stage preangiogenic AMD, soft drusen, and elevated blood factors were at risk for substantial visual loss. A sample size larger than 43 patients is important to provide a basis for widespread adoption of novel therapeutic options for AMD such as Rheopheresis. Therefore, enrollment to 150 patients is continuing.

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Selected References

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  1. Attebo K., Mitchell P., Smith W. Visual acuity and the causes of visual loss in Australia. The Blue Mountains Eye Study. Ophthalmology. 1996 Mar;103(3):357–364. doi: 10.1016/s0161-6420(96)30684-2. [DOI] [PubMed] [Google Scholar]
  2. Berrouschot J., Barthel H., Scheel C., Köster J., Schneider D. Extracorporeal membrane differential filtration--a new and safe method to optimize hemorheology in acute ischemic stroke. Acta Neurol Scand. 1998 Feb;97(2):126–130. doi: 10.1111/j.1600-0404.1998.tb00621.x. [DOI] [PubMed] [Google Scholar]
  3. Blumenkranz M. S., Russell S. R., Robey M. G., Kott-Blumenkranz R., Penneys N. Risk factors in age-related maculopathy complicated by choroidal neovascularization. Ophthalmology. 1986 May;93(5):552–558. doi: 10.1016/s0161-6420(86)33702-3. [DOI] [PubMed] [Google Scholar]
  4. Bressler N. M., Bressler S. B. Preventative ophthalmology. Age-related macular degeneration. Ophthalmology. 1995 Aug;102(8):1206–1211. doi: 10.1016/s0161-6420(95)30889-5. [DOI] [PubMed] [Google Scholar]
  5. Brunner R., Widder R. A., Fischer R. A., Walter P., Bartz-Schmidt K. U., Heimann K., Borberg H. Clinical efficacy of haemorheological treatment using plasma exchange, selective adsorption and membrane differential filtration in maculopathy, retinal vein occlusion and uveal effusion syndrome. Transfus Sci. 1996 Dec;17(4):493–498. [PubMed] [Google Scholar]
  6. Brunner R., Widder R. A., Walter P., Borberg H., Oette K. Change in hemorrheological and biochemical parameters following membrane differential filtration. Int J Artif Organs. 1995 Dec;18(12):794–798. [PubMed] [Google Scholar]
  7. Brunner R., Widder R. A., Walter P., Lüke C., Godehardt E., Bartz-Schmidt K. U., Heimann K., Borberg H. Influence of membrane differential filtration on the natural course of age-related macular degeneration: a randomized trial. Retina. 2000;20(5):483–491. doi: 10.1097/00006982-200009000-00009. [DOI] [PubMed] [Google Scholar]
  8. Brunner T. Making an impression of a partially edentulous jaw with separable individual impression trays made of resin material. Quintessence Int (Berl) 1970 Jun;1(6):31–34. [PubMed] [Google Scholar]
  9. Ciulla T. A., Harris A., Chung H. S., Danis R. P., Kagemann L., McNulty L., Pratt L. M., Martin B. J. Color Doppler imaging discloses reduced ocular blood flow velocities in nonexudative age-related macular degeneration. Am J Ophthalmol. 1999 Jul;128(1):75–80. doi: 10.1016/s0002-9394(99)00061-6. [DOI] [PubMed] [Google Scholar]
  10. Ciulla T. A., Harris A., Danis R. P. Presumed macular choroidal watershed vascular filling, choroidal neovascularization, and systemic vascular disease in patients with age-related macular degeneration. Am J Ophthalmol. 1998 Jul;126(1):153–155. doi: 10.1016/s0002-9394(98)00233-5. [DOI] [PubMed] [Google Scholar]
  11. Fine S. L., Berger J. W., Maguire M. G., Ho A. C. Age-related macular degeneration. N Engl J Med. 2000 Feb 17;342(7):483–492. doi: 10.1056/NEJM200002173420707. [DOI] [PubMed] [Google Scholar]
  12. Friedman E. A hemodynamic model of the pathogenesis of age-related macular degeneration. Am J Ophthalmol. 1997 Nov;124(5):677–682. doi: 10.1016/s0002-9394(14)70906-7. [DOI] [PubMed] [Google Scholar]
  13. Friedman E., Krupsky S., Lane A. M., Oak S. S., Friedman E. S., Egan K., Gragoudas E. S. Ocular blood flow velocity in age-related macular degeneration. Ophthalmology. 1995 Apr;102(4):640–646. doi: 10.1016/s0161-6420(95)30974-8. [DOI] [PubMed] [Google Scholar]
  14. Furuta M., Shimizu T., Mizuno S., Kamiya T., Ozawa K., Nakase T., Tadokoro K., Takenaka M., Ohkawa T., Yokoyama S. Clinical evaluation of repeat apheresis donors in Japan. Vox Sang. 1999;77(1):17–23. doi: 10.1159/000031069. [DOI] [PubMed] [Google Scholar]
  15. Goldberg J., Flowerdew G., Smith E., Brody J. A., Tso M. O. Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol. 1988 Oct;128(4):700–710. doi: 10.1093/oxfordjournals.aje.a115023. [DOI] [PubMed] [Google Scholar]
  16. Grunwald J. E., Hariprasad S. M., DuPont J., Maguire M. G., Fine S. L., Brucker A. J., Maguire A. M., Ho A. C. Foveolar choroidal blood flow in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1998 Feb;39(2):385–390. [PubMed] [Google Scholar]
  17. Hirvelä H., Luukinen H., Lärä E., Sc L., Laatikainen L. Risk factors of age-related maculopathy in a population 70 years of age or older. Ophthalmology. 1996 Jun;103(6):871–877. doi: 10.1016/s0161-6420(96)30593-9. [DOI] [PubMed] [Google Scholar]
  18. Hyman L. G., Lilienfeld A. M., Ferris F. L., 3rd, Fine S. L. Senile macular degeneration: a case-control study. Am J Epidemiol. 1983 Aug;118(2):213–227. doi: 10.1093/oxfordjournals.aje.a113629. [DOI] [PubMed] [Google Scholar]
  19. Johnson L. V., Ozaki S., Staples M. K., Erickson P. A., Anderson D. H. A potential role for immune complex pathogenesis in drusen formation. Exp Eye Res. 2000 Apr;70(4):441–449. doi: 10.1006/exer.1999.0798. [DOI] [PubMed] [Google Scholar]
  20. Kahn H. A., Leibowitz H. M., Ganley J. P., Kini M. M., Colton T., Nickerson R. S., Dawber T. R. The Framingham Eye Study. II. Association of ophthalmic pathology with single variables previously measured in the Framingham Heart Study. Am J Epidemiol. 1977 Jul;106(1):33–41. doi: 10.1093/oxfordjournals.aje.a112429. [DOI] [PubMed] [Google Scholar]
  21. Kaul D. Molecular link between cholesterol, cytokines and atherosclerosis. Mol Cell Biochem. 2001 Mar;219(1-2):65–71. doi: 10.1023/a:1011006707414. [DOI] [PubMed] [Google Scholar]
  22. Klaver C. C., Wolfs R. C., Vingerling J. R., Hofman A., de Jong P. T. Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study. Arch Ophthalmol. 1998 May;116(5):653–658. doi: 10.1001/archopht.116.5.653. [DOI] [PubMed] [Google Scholar]
  23. Klein R., Klein B. E., Franke T. The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1993 Mar;100(3):406–414. doi: 10.1016/s0161-6420(93)31634-9. [DOI] [PubMed] [Google Scholar]
  24. Klingel R., Fassbender C., Fassbender T., Erdtracht B., Berrouschot J. Rheopheresis: rheologic, functional, and structural aspects. Ther Apher. 2000 Oct;4(5):348–357. doi: 10.1046/j.1526-0968.2000.004005348.x. [DOI] [PubMed] [Google Scholar]
  25. Lanchoney D. M., Maguire M. G., Fine S. L. A model of the incidence and consequences of choroidal neovascularization secondary to age-related macular degeneration. Comparative effects of current treatment and potential prophylaxis on visual outcomes in high-risk patients. Arch Ophthalmol. 1998 Aug;116(8):1045–1052. doi: 10.1001/archopht.116.8.1045. [DOI] [PubMed] [Google Scholar]
  26. Langham M. E., Farrell R. A., O'Brien V., Silver D. M., Schilder P. Blood flow in the human eye. Acta Ophthalmol Suppl. 1989;191:9–13. doi: 10.1111/j.1755-3768.1989.tb07080.x. [DOI] [PubMed] [Google Scholar]
  27. Lip P. L., Blann A. D., Hope-Ross M., Gibson J. M., Lip G. Y. Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction. Ophthalmology. 2001 Apr;108(4):705–710. doi: 10.1016/s0161-6420(00)00663-1. [DOI] [PubMed] [Google Scholar]
  28. Maltzman B. A., Mulvihill M. N., Greenbaum A. Senile macular degeneration and risk factors: a case-control study. Ann Ophthalmol. 1979 Aug;11(8):1197–1201. [PubMed] [Google Scholar]
  29. Mares-Perlman J. A., Brady W. E., Klein R., VandenLangenberg G. M., Klein B. E., Palta M. Dietary fat and age-related maculopathy. Arch Ophthalmol. 1995 Jun;113(6):743–748. doi: 10.1001/archopht.1995.01100060069034. [DOI] [PubMed] [Google Scholar]
  30. Mullins R. F., Aptsiauri N., Hageman G. S. Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis. Eye (Lond) 2001 Jun;15(Pt 3):390–395. doi: 10.1038/eye.2001.142. [DOI] [PubMed] [Google Scholar]
  31. Mullins R. F., Russell S. R., Anderson D. H., Hageman G. S. Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J. 2000 May;14(7):835–846. [PubMed] [Google Scholar]
  32. Piguet B., Palmvang I. B., Chisholm I. H., Minassian D., Bird A. C. Evolution of age-related macular degeneration with choroidal perfusion abnormality. Am J Ophthalmol. 1992 Jun 15;113(6):657–663. doi: 10.1016/s0002-9394(14)74790-7. [DOI] [PubMed] [Google Scholar]
  33. Ross R. D., Barofsky J. M., Cohen G., Baber W. B., Palao S. W., Gitter K. A. Presumed macular choroidal watershed vascular filling, choroidal neovascularization, and systemic vascular disease in patients with age-related macular degeneration. Am J Ophthalmol. 1998 Jan;125(1):71–80. doi: 10.1016/s0002-9394(99)80237-2. [DOI] [PubMed] [Google Scholar]
  34. Sarraf D., Gin T., Yu F., Brannon A., Owens S. L., Bird A. C. Long-term drusen study. Retina. 1999;19(6):513–519. doi: 10.1097/00006982-199911000-00006. [DOI] [PubMed] [Google Scholar]
  35. Seddon J. M., Rosner B., Sperduto R. D., Yannuzzi L., Haller J. A., Blair N. P., Willett W. Dietary fat and risk for advanced age-related macular degeneration. Arch Ophthalmol. 2001 Aug;119(8):1191–1199. doi: 10.1001/archopht.119.8.1191. [DOI] [PubMed] [Google Scholar]
  36. Seddon J. M., Willett W. C., Speizer F. E., Hankinson S. E. A prospective study of cigarette smoking and age-related macular degeneration in women. JAMA. 1996 Oct 9;276(14):1141–1146. [PubMed] [Google Scholar]
  37. Smith W., Mitchell P., Leeder S. R. Smoking and age-related maculopathy. The Blue Mountains Eye Study. Arch Ophthalmol. 1996 Dec;114(12):1518–1523. doi: 10.1001/archopht.1996.01100140716016. [DOI] [PubMed] [Google Scholar]
  38. Smith W., Mitchell P., Leeder S. R., Wang J. J. Plasma fibrinogen levels, other cardiovascular risk factors, and age-related maculopathy: the Blue Mountains Eye Study. Arch Ophthalmol. 1998 May;116(5):583–587. doi: 10.1001/archopht.116.5.583. [DOI] [PubMed] [Google Scholar]
  39. Smith W., Mitchell P., Leeder S. R., Wang J. J. Plasma fibrinogen levels, other cardiovascular risk factors, and age-related maculopathy: the Blue Mountains Eye Study. Arch Ophthalmol. 1998 May;116(5):583–587. doi: 10.1001/archopht.116.5.583. [DOI] [PubMed] [Google Scholar]
  40. Sperduto R. D., Hiller R. Systemic hypertension and age-related maculopathy in the Framingham Study. Arch Ophthalmol. 1986 Feb;104(2):216–219. doi: 10.1001/archopht.1986.01050140070022. [DOI] [PubMed] [Google Scholar]
  41. Vingerling J. R., Dielemans I., Bots M. L., Hofman A., Grobbee D. E., de Jong P. T. Age-related macular degeneration is associated with atherosclerosis. The Rotterdam Study. Am J Epidemiol. 1995 Aug 15;142(4):404–409. doi: 10.1093/oxfordjournals.aje.a117648. [DOI] [PubMed] [Google Scholar]
  42. Vucic S., Davies L. Safety of plasmapheresis in the treatment of neurological disease. Aust N Z J Med. 1998 Jun;28(3):301–305. doi: 10.1111/j.1445-5994.1998.tb01952.x. [DOI] [PubMed] [Google Scholar]
  43. Zhao J., Frambach D. A., Lee P. P., Lee M., Lopez P. F. Delayed macular choriocapillary circulation in age-related macular degeneration. Int Ophthalmol. 1995;19(1):1–12. doi: 10.1007/BF00156412. [DOI] [PubMed] [Google Scholar]

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