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Transplantation von retinalem Pigmentepithel (RPE) nach CNV-Exzision bei altersabhängiger Makuladegeneration

Techniken, Ergebnisse und Perspektiven

Transplantation of retinal pigment pithelium (RPE) following CNV removal in patients with AMD

Techniques, results, outlook

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Zusammenfassung

Subfoveale choroidale Neovaskularisationen (CNV) sind neben der geographischen Atrophie heute die häufigste Ursache für einen irreversiblen Verlust der zentralen Sehschärfe bei altersabhängiger Makuladegeneration (AMD). Chirurgisch kann eine subfoveale CNV mittels vitreoretinaler Techniken über eine paramakuläre Retinotomie exzidiert werden. Dies ist allerdings in der Regel mit einer gleichzeitigen Entfernung des korrespondierenden retinalen Pigmentepithels (RPE) verbunden. Zur Vermeidung eines konsekutiven Zentralskotoms umfassten bisherige Ansätze zur RPE-Zelltransplantation nach CNV-Exzision die Injektion sowohl heterologer als auch autologer RPE-Zellsuspensionen, die jedoch mit Dedifferenzierung der RPE-Zellen, ausbleibender Bildung einer regulären Adhäsion an die Bruch’sche Membran und eines einschichtigen Zellrasens einhergingen. In jüngster Zeit wurden daher Translokationstechniken mit autologen RPE-Sheets mit intakter Polarität entwickelt, die den Erhalt der fovealen Netzhautfunktion erlaubten. Dabei wird außerhalb der Makula ein RPE/Bruch’Membran/Aderhaut-Komplex gewonnen und intraokular unter die Makula transloziert. Neben den aktuellen pharmakologischen Ansätzen inkl. Anti-VEGF-Präparaten eröffnen sich mit diesen mikrochirurgischen Verfahren neue therapeutische Perspektiven für Patienten mit subfovealer CNV.

Abstract

Neovascular age-related macular degeneration (AMD) has become the leading cause for severe visual loss in all industrialized nations. Surgical excision of choroidal neovascularizations (CNV) is technically feasible but invariably associated with inadvertent removal of corresponding retinal pigment epithelium (RPE) and subsequent atrophy of the choriocapillaris, with the latter two layers being a prerequisite for normal photoreceptor function. To cover the RPE defect both heterologous and homologous RPE cell suspensions have been injected into the subretinal space. The lack of functional improvement has been attributed to various factors including RPE cell dedifferentiation, failure of adherence to Bruch’s membrane as well as development of a regular RPE cell monolayer. Therefore, techniques for translocating intact autologous RPE cell sheets have been sought and preservation of foveal neurosensory functions has recently been successfully demonstrated. Besides translocation of a full-thickness RPE/Bruch’s membrane/choroid patch outside the macular area, superfluous choroidal tissue may be ablated intraocularly using an excimer laser prior to translocation. Besides recent pharmacological approaches including anti-VEGF agents, these surgical developments open new perspectives for patients with neovascular AMD.

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Literatur

  1. Abdel-Meguid A, Lappas A, Hartmann K, Auer F, Schrage N, Thumann G, Kirchhof B (2003) One year follow up of macular translocation with 360 degree retinotomy in patients with age related macular degeneration. Br J Ophthalmol 87:615–621

    Article  CAS  PubMed  Google Scholar 

  2. Aisenbrey S, Lafaut BA, Szurman P et al. (2002) Macular translocation with 360 degrees retinotomy for exudative age-related macular degeneration. Arch Ophthalmol 120:451–459

    PubMed  Google Scholar 

  3. Algvere PV, Berglin L, Gouras P, Sheng Y, Kopp ED (1997) Transplantation of RPE in age-related macular degeneration observations in disciform lesions and dry atrophy. Graefes Arch Clin Exp Ophthalmol 235:149–158

    CAS  PubMed  Google Scholar 

  4. Algvere PV, Berlin L, Gouras P, Sheng Y (1994) Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefes Arch Clin Exp Ophthalmol 232:707–716

    CAS  PubMed  Google Scholar 

  5. Algvere PV, Gouras P, Dafgard Kopp E (1999) Long-term outcome allografts in non-immunosuppressed patients with AMD. Eur J Ophthalmol 9:217–230

    CAS  PubMed  Google Scholar 

  6. Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP (2003) Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol 48:257–293

    Article  PubMed  Google Scholar 

  7. Berglin L, Gouras P, Sheng Y, Lavid J, Lin PK, Cao H, Kjeldbye H (1997) Tolerance of human fetal retinal pigment epithelium xenografts in monkey retina. Graefes Arch Clin Exp Ophthalmol 235:103–110

    CAS  PubMed  Google Scholar 

  8. Binder S, Stolba U, Krebs I et al. (2002) Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization resulting from age-related macular degeneration: a pilot study. Am J Ophthalmol 133:215–225

    Article  PubMed  Google Scholar 

  9. Bindewald A, Jorzik JJ, Loesch A, Schutt F, Holz FG (2004) Visualisation of retinal pigment epithelial (RPE) cells in vivo using digital high resolution confocal scanning laser ophthalmoscopy. Am J Ophthalmol 137:556–558

    Article  PubMed  Google Scholar 

  10. Bindewald A, Schutt F, Specht H, Holz FG (2003) Preclinical study for intraocular microablation of choroidal tissue using a 308 nm UV excimer laser for RPE-sheet translocation. ARVO #500

  11. Bird AC (1996) Age-related macular disease. Br J Ophthalmol 80:1–2

    PubMed  Google Scholar 

  12. Bressler NM, Bressler SB (1995) Preventative ophthalmology. Age-related macular degeneration. Ophthalmology 102:1206–1211

    CAS  PubMed  Google Scholar 

  13. Bressler NM, Frost LA, Bressler SB, Murphy RP, Fine SL (1988) Natural course of poorly defined choroidal neovascularization associated with macular degeneration. Arch Ophthalmol 106:1537–1542

    CAS  PubMed  Google Scholar 

  14. Brody BL, Roch-Levecq AC, Gamst AC, Maclean K, Kaplan RM, Brown SI (2002) Self-management of age-related macular degeneration and quality of life: a randomized controlled trial. Arch Ophthalmol 120:1477–1483

    PubMed  Google Scholar 

  15. Challa JK, Gillies MC, Penfold PL (1998) Exsudative degeneration and intravitreal triamcinolone: 18 month follow up. Aust N Z J Ophthalmol 26:277–281

    Article  CAS  PubMed  Google Scholar 

  16. D’Amato RJ, Loughan MS, Flynn E, Folkman J (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 91:4082–4085

    PubMed  Google Scholar 

  17. De Juan E, Fujii GY (2001) Limited macular translocation. Eye 15:413–423

    PubMed  Google Scholar 

  18. De Juan E, Loewenstein A, Bressler NM, Alexander J (1998) Translocation of the retina for management of subfoveal choroidal neovascularization II: A preliminary report in humans. Am J Ophthalmol 125:635–645

    Article  PubMed  Google Scholar 

  19. Eckardt C, Eckardt U, Conrad H-G (1999) Macular rotation with and without counter-rotation of the globe in patients with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 237:313–325

    Article  CAS  PubMed  Google Scholar 

  20. El Dirini AA, Wang HM, Odgen TE, Ryan SJ (1992) Retinal pigment epithelium implantation in the rabbit: technique and morphology. Graefes Arch Clin Exp Ophthalmol 230:292–300

    PubMed  Google Scholar 

  21. Faude F, Wendt S, Biedermann B et al. (2001) Facilitation of artificial retinal detachment for macular translocation surgery tested in rabbit. Invest Ophthalmol Vis Sci 42:1328–1337

    CAS  PubMed  Google Scholar 

  22. Fauser S, Engelmann K, Krohne TU, Lappas A, Kirchhof B, Joussen AM (2003) Pathogenese der choroidalen Neovaskularisation. Alte Konzepte, neue Fragen. Ophthalmologe100:300–305

  23. Frank RN, Amin RH, Eliott D, Puklin JE, Abrams GW (1996) Basic fibroblast growth factor and vascular endothelial growth factor are present in epiretinal and choroidal neovascular membranes. Am J Ophthalmol 122:393–403

    CAS  PubMed  Google Scholar 

  24. Freedman SF, Seaber JH, Buckley EG, Enyedi LB, Toth CA (2000) Combined superior oblique muscle recession and inferior oblique muscle advancement and transposition for cyclotorsion associated with macular translocation surgery. J AAPOS 4:75–83

    Article  CAS  PubMed  Google Scholar 

  25. Freund KB, Yannuzzi LA, Sorenson JA (1993) Age-related macular degeneration and choroidal neovascularization. Am J Ophthalmol 115:786–791

    CAS  PubMed  Google Scholar 

  26. Fujii GY, Pieramici DJ, Humayun MS, Schachat AP, Reynolds SM, Melia M, De Juan E (2000) Complications associated with limited macular translocation. Am J Ophthalmol 130:751–762

    Article  CAS  PubMed  Google Scholar 

  27. Gouras P, Flood MT, Kjeldbye H, Bilek MK, Eggers H (1985) Transplantation of cultured human retinal epithelium to Bruch’s membrane of the owl monkey’s eye. Curr Eye Res 4:253–265

    CAS  PubMed  Google Scholar 

  28. Grossniklaus HE, Gass JD (1998) Clinicopathologic correlations of surgically excised type 1 and type 2 submacular choroidal neovascular membranes. Am J Ophthalmol 126:59–69

    Article  CAS  PubMed  Google Scholar 

  29. He S, Wang HM, Odgen TE, Ryan SJ (1993) Transplantation of cultured human retinal pigment epithelium into rabbit subretina. Graefes Arch Clin Exp Ophthalmol 231:737–742

    CAS  PubMed  Google Scholar 

  30. Holz FG, Bellmann C, Staudt S, Schutt F, Volcker HE (2001) Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. Invest Ophthalmol Vis Sci 42:1051–1056

    CAS  PubMed  Google Scholar 

  31. Holz FG, Bindewald A, Schutt F, Specht H (2003) Microablation of choroidal tissue by a 308 nm AIDA Excimer laser for RPE transplantation in patients with age-related macular degeneration. Biomed Tech 48:82–85

    CAS  Google Scholar 

  32. Holz FG, Pauleikhoff D, Klein R, Bird AC (2004) Pathogenesis of lesions in late age-related macular disease. Am J Ophthalmol 137:504–510

    Article  PubMed  Google Scholar 

  33. Holz FG, Schütt F, Specht H (2003) Microablation of choroidal tissue by a 308 nm AIDA Excimer laser for RPE transplantaion in patients with age-related macular degeneration. Biomed Tech 48:82–85

    CAS  Google Scholar 

  34. Hudson HL, Frambach DA, Lopez PF (1995) Relation of the functional and structural fundus changes after submacular surgery for neovascular age-related macular degeneration. Br J Ophthalmol 79:417–423

    CAS  PubMed  Google Scholar 

  35. Hyman LG, Lilienfeld AM, Ferris FL, Fine SL (1983) Senile macular degeneration: a case control study. Am J Epidemiol 118:213–227

    CAS  PubMed  Google Scholar 

  36. Jonas JB, Kreissig I, Hugger P, Sauder G, Panda-Jonas S, Degenring R (2003) Intravitreal triamcinolone acetonide for exudative age related macular degeneration. Br J Ophthalmol 87:462–468

    Article  CAS  PubMed  Google Scholar 

  37. Klaver CCW, van Leeuwen R, Vingerling JR, De Jong PTVM (2003) Epidemiology of age-related maculopathy. In: Holz FG, Pauleikhoff D, Spaide RF, Bird AC (Hrsg) Age-related macular degeneration. Springer, Berlin Heidelberg New York Tokyo

  38. Lavail MM, Li L, Turner JE, Yasumura D (1992) Retinal pigment epithelial cell transplantation in RCS rats: normal metabolism in rescued photoreceptors. Exp Eye Res 55:555–562

    CAS  PubMed  Google Scholar 

  39. Lee CJ, Bent SF, Blumenkranz MS, Fishman HA (2003) RPE cell adhesion on spatially patterned lens capsule. ARVO #501

  40. Lewis H, Kaiser PK, Lewis S, Estafanous M (1999) Macular translocation for subfoveal choroidal neovascularization in age-related macular degeneration: a prospective study. Am J Ophthalmol 128:135–146

    Article  CAS  PubMed  Google Scholar 

  41. Li LX, Sheedlo HJ, Turner JE (1990) Long-term rescue of photoreceptor cells in the retinas of RCS dystrophic rats by RPE transplants. Prog Brain Res 82:179–185

    CAS  PubMed  Google Scholar 

  42. Lopez R, Gouras P, Brittis M, Kjeldbye H (1997) Transplantation of cultured rabbit retinal epithelium to rabbit retina using a closed-eye method. Invest Ophthalmol Vis Sci 28:1131–1137

    Google Scholar 

  43. Machemer R, Steinhorst UH (1993) Retinal separation, retinotomy, and macular relocation: II. A surgical approach for age-related macular degeneration? Graefes Arch Clin Exp Ophthalmol 231:635–641

    CAS  PubMed  Google Scholar 

  44. Miller DW, Joussen AM, Holz FG (2003) Die molekularen Mechanismen der neovaskulären AMD. Ophthalmologe 100:92–96

    Article  CAS  PubMed  Google Scholar 

  45. Nicolini J, Kiilgaard JF, Wiencke AK, Heegaard S, Scherfig E, Prause JU, la Cour M (2000) The anterior lens capsule used as support material in RPE cell-transplantation. Acta Ophthalmol Scand 78:527–531

    Article  CAS  PubMed  Google Scholar 

  46. Ohji M, Fujikado T, Kusaka S et al. (2001) Comparison of three techniques of foveal translocation in patients with subfoveal choroidal neovascularization resulting from age-related macular degeneration. Am J Ophthalmol 132:888–896

    Article  CAS  PubMed  Google Scholar 

  47. Pertile G, Claes C (2002) Macular translocation with 360 degree retinotomy for management of age-related macular degeneration with subfoveal choroidal neovascularization. Am J Ophthalmol 134:560–565

    Article  PubMed  Google Scholar 

  48. Pharmacological therapy for macular degeneration study group (1997) Interferon-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration. Results of a prospective randomized placebo-controlled clinical trial. Arch Ophthalmol 115:865–872

    PubMed  Google Scholar 

  49. Roth F, Bindewald A, Holz FG (2004) Pathophysiologic pathways in age-related macular disease. Graefes Arch Clin Exp Ophthalmol, Im Druck

  50. Rovner BW, Casten RJ, Tasman WS (2002) Effect of depression on vision function in age-related macular degeneration. Arch Ophthalmol 120:1041–1044

    PubMed  Google Scholar 

  51. Scheider A, Gundisch O, Kampik A (1999) Surgical extraction of subfoveal choroidal new vessels and submacular haemorrhage in age-related macular degeneration: results of a prospective study. Graefes Arch Clin Exp Ophthalmol 237:10–15

    Article  CAS  PubMed  Google Scholar 

  52. Schmitz-Valckenberg S, Bültmann S, Bindewald A, Mansmann U, Holz FG, Rohrschneider K (2004) Fundus autofluorescence and fundus perimetry in the junctional zone of geographic atrophy in patients with age-related macular degeneration. Zur Publikation eingereicht

  53. Schütt F, Holz FG (2002) Microablation of choroidal tissue from Bruch’s membrane using a 193 nm excimer laser. Exp Eye Res 74:155–157

    Article  PubMed  Google Scholar 

  54. Stanga PE, Kychenthal A, Fitzke FW, Halfyard AS, Chan R, Bird AC, Aylward GW (2001) Retinal pigment epithelium translocation and central visual function in age related macular degeneration: preliminary results. Int Ophthalmol 23:297–307

    Article  CAS  PubMed  Google Scholar 

  55. Stanga PE, Kychenthal A, Fitzke FW, Halfyard AS, Chan R, Bird AC, Aylward GW (2002) Retinal pigment epithelium translocation after choroidal neovascular membrane removal in age-related macular degeneration. Ophthalmology 109:1492–1498

    Article  PubMed  Google Scholar 

  56. Thomas MA, Dickinson JD, Melberg NS, Ibanez HE, Dhaliwal RS (1994) Visual results after surgical removal of subfoveal choroidal neovascular membranes. Ophthalmology 101:1384–1396

    CAS  PubMed  Google Scholar 

  57. Thomas MA, Grand MG, Williams DF, Lee CM, Pesin SR, Lowe MA (1992) Surgical management of subfoveal choroidal neovascularization. Ophthalmology 99:952–968

    CAS  PubMed  Google Scholar 

  58. Thomas MA, Ibanez HE (1993) Interferon alfa-2 in the treatment of subfoveal choroidal neovascularization. Am J Ophthalmol 115:563–568

    CAS  PubMed  Google Scholar 

  59. Thumann G, Schaefer F, Theofylaktopoulos I, Kirchhof B (2004) Transplantation to the subretinal space of pigment epithelial cells cultured on ultrathin collagen sheets. ARVO #3108

  60. Thumann G, Schraermeyer U, Bartz-Schmidt KU, Heimann K (1997) Descemet’s membrane as membranous support in RPE/IPE transplantation. Curr Eye Res 16:1236–1238

    Article  CAS  PubMed  Google Scholar 

  61. Toth C, Machemer R (1999) Macular translocation. In Fine, McGuire RE, Berger W (eds) Age-related macular degeneration. Mosby, St. Louis, S 353–362

  62. Toth CA, Freedman SF (2001) Macular translocation with 360-degree peripheral retinectomy impact of technique and surgical experience on visual outcomes. Retina 21:293–303

    Article  CAS  PubMed  Google Scholar 

  63. Trauzettel-Klosinski S (2003) Reading with AMD. In: Holz FG, Pauleikhoff D, Spaide RF, Bird AC (Hrsg) Age-related macular degeneration. Springer, Berlin Heidelberg New York Tokyo

  64. Van Meurs JC, Maaijwee K, van den Biesen PR et al. (2004) Translocation of autologous retinal pigment epithelium and choroid in patients with exudative age-related macular degeneration: further follow-up. ARVO #4628

  65. Van Meurs JC, Ter Averst E, Croxen R, Hofland L, Van Hagen PM (2004) Comparison of the growth potential of retinal pigment epithelial cells obtained during vitrectomy in patients with age-related macular degeneration or complex retinal detachment. Graefes Arch Clin Exp Ophthalmol 242:442–423

    PubMed  Google Scholar 

  66. Van Meurs JC, ter Averst E, Hofland LJ et al. (2004) Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes. Br J Ophthalmol 88:110–113

    Article  PubMed  Google Scholar 

  67. Van Meurs JC, van den Biesen PR (2003) Autologous retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: short-term follow-up. Am J Ophthalmol 136:688–695

    Article  PubMed  Google Scholar 

  68. Von Ruckmann A, Fitzke FW, Bird AC (1997) Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope. Invest Ophthalmol Vis Sci 38:478–486

    PubMed  Google Scholar 

  69. Wolf S, Lappas A, Weinberger AW, Kirchhof B (1999) Macular translocation for surgical management of subfoveal choroidal neovascularizations in patients with AMD: first results. Graefes Arch Clin Exp Ophthalmol 237:51–57

    Article  CAS  PubMed  Google Scholar 

  70. Wong D, Lois N (2000) Foveal relocation by redistribution of the neurosensory retina. Br J Ophthalmol 84:352–357

    Article  CAS  PubMed  Google Scholar 

  71. Yamamoto S, Du J, Gouras P, Kjeldbye H (1993) Retinal pigment epithelial transplants and retinal function in RCS rats. Invest Ophthalmol Vis Sci 34:3068–3075

    CAS  PubMed  Google Scholar 

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Bindewald, A., Roth, F., van Meurs, J. et al. Transplantation von retinalem Pigmentepithel (RPE) nach CNV-Exzision bei altersabhängiger Makuladegeneration. Ophthalmologe 101, 886–894 (2004). https://doi.org/10.1007/s00347-004-1077-2

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