Download PDF
Klin Monbl Augenheilkd 2008; 225(8): 699-702
DOI: 10.1055/s-2008-1027451
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Nichtmedikamentöse interventionelle Perspektiven bei der AMD

Non-Pharmacological Interventional Perspectives in AMDG. Thumann1, 2 , P. Walter2
  • 1IZKF Biomat, RWTH Aachen
  • 2Universitätsaugenklinik, RWTH Aachen
Further Information

Publication History

Eingegangen: 11.3.2008

Angenommen: 26.3.2008

Publication Date:
19 August 2008 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die chirurgische Behandlung der AMD durch Zelltransplantation und Makularotation wurde bereits vor über 25 Jahren entwickelt. Aktuell wird die Injektionstherapie mit Inhibitoren von Wachstumsfaktoren erfolgreich angewendet. Dabei kann in etwa 30 % der Fälle eine Visusverbesserung erreicht werden. Grundsätzlich gelten für eine erfolgreiche Therapie mit Wachstumsfaktorinhibitoren als Voraussetzung: 1. Die RPE-Zellen müssen vorhanden und funktionstüchtig sein. 2. Die Photorezeptorzellen dürfen nicht degeneriert sein. Nach dieser Hypothese kann eine antivaskuläre Injektionstherapie anderenfalls nicht funktionieren und eine chirurgische Intervention ist dann indiziert. Da die chirurgische Entfernung von RPE-Zellen und Gefäßmembranen bei der AMD zu einer Zerstörung von Teilen der Basalmembran sowie der Bruch’schen Membran führt, erscheint eine Rekonstruktion dieser Schichten für eine erfolgreiche Therapie von entscheidender Bedeutung zu sein. Nach aktueller Studienlage zeigt die Makularotation die besten Langzeitergebnisse und stellt damit das chirurgische Verfahren der Wahl dar. Die Transplantation von RPE- oder IPE-Zellen bei AMD-Patienten hat demgegenüber bislang nicht zu einer signifikanten Visusverbesserung geführt. Unter den vielen möglichen Verfahren zur Rekonstruktion der zerstörten Basalmembran und der Bruch’schen Membran erscheint zukünftig die Verwendung eines Monolayers von Pigmentepithelzellen auf einem biologisch abbaubaren Substrat als das Erfolg versprechendste Verfahren. Außerdem können die transplantierten Zellen innerhalb des Monolayers genetisch gezielt modifiziert werden, um eine Rekonstruktion des Netzhaut-Aderhautkomplexes mittels Wachstumsfaktoren oder Inhibitoren von Neovaskularisationen zu unterstützen.

Abstract

Transplantation and translocation surgery for the treatment of AMD has been evaluated for over 25 years. More recently injections of inhibitors of vascularisation have been used with some success. Inhibitors of neovascularisation result in the recovery of vision in about 30 % of patients; however, we do not understand what criteria can be used to select patients who will respond to or will not respond to treatment with antivascularisation treatment. We have to assume that successful antivascularisation treatment will require first that the retinal pigment epithelial cells be present and functional and second that the photoreceptor cells should not be degenerated. We then hypothesise that if either of these two parameters are not present, antivascular treatment will not result in vision recovery and we must then consider surgical intervention. Surgical intervention for macular degeneration encompasses procedures from simple membrane extraction to macular rotation to cell transplantation or a combination of these procedures, however these procedures must take into account that vision recovery cannot be achieved without reconstruction of the retina-choroid complex. Since in AMD degeneration of the retinal pigment epithelial cells and vascular membranes removal results in damage to the basal lamina and possibly deeper layers of Bruch’s membrane, it will be necessary to reconstruct these damaged structures. In fact, transplantation of RPE cells or IPE cells has not resulted in any significant improvement in vision in AMD patients. Long-term follow-up of AMD patients following macular rotation surgery has shown that significant visual recovery is not maintained in most patients. Of the many approaches that could be used to reconstruct the damaged basal lamina and Bruch’s membrane the most promising would be the introduction of a monolayer of pigment cells on a “natural” biodegradable substratum. A natural substratum consisting of extracellular matrix proteins would allow the pigment cells to retain their differentiated characteristics and functions, including the degradation the substratum and production of the normal components of the basal lamina and Bruch’s membrane. In addition, the cells introduced as a monolayer can be engineered to carry specific genes to aid in the restructuring of the retina-choroid complex, such as growth factors and inhibitors of vascularisation.

Schlüsselwörter

Retina - Chorioidea - Glaskörper

Key words

retina - choroid - vitreous

Literatur

  • 1 Abe T, Yoshida M, Kano T. et al . Visual function after removal of subretinal neovascular membranes in patients with age-related macular degeneration.  Graefes Arch Clin Exp Ophthalmol. 2001;  239 (12) 927-936
    Google Scholar
  • 2 Aisenbrey S, Bartz-Schmidt K U, Walter P. et al . Long-term follow-up of macular translocation with 360 degrees retinotomy for exudative age-related macular degeneration.  Arch Ophthalmol. 2007;  125 (10) 1367-1372
    Google Scholar
  • 3 Aisenbrey S, Lafaut B A, Szurman P. et al . Macular translocation with 360 degrees retinotomy for exudative age-related macular degeneration.  Arch Ophthalmol. 2002;  120 (4) 451-459
    Google Scholar
  • 4 Aisenbrey S, Lafaut B A, Szurman P. et al . Iris pigment epithelial translocation in the treatment of exudative macular degeneration: a 3-year follow-up.  Arch Ophthalmol. 2006;  124 (2) 183-188
    Google Scholar
  • 5 Algvere P V, Berglin L, Gouras P. et al . Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization.  Graefes Arch Clin Exp Ophthalmol. 1994;  232 (12) 707-716
    Google Scholar
  • 6 Algvere P V, Gouras P, Dafgard K E. Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD.  Eur J Ophthalmol. 1999;  9 (3) 217-230
    Google Scholar
  • 7 bdel-Meguid A, Lappas A, Hartmann K. et al . One year follow up of macular translocation with 360 degree retinotomy in patients with age related macular degeneration.  Br J Ophthalmol. 2003;  87 (5) 615-621
    Google Scholar
  • 8 Cahill M T, Freedman S F, Toth C A. Macular translocation with 360 degrees peripheral retinectomy for geographic atrophy.  Arch Ophthalmol. 2003;  121 (1) 132-133
    Google Scholar
  • 9 Cahill M T, Mruthyunjaya P, Bowes R C. et al . Recurrence of retinal pigment epithelial changes after macular translocation with 360 degrees peripheral retinectomy for geographic atrophy.  Arch Ophthalmol. 2005;  123 (7) 935-938
    Google Scholar
  • 10 Campochiaro P A, Nguyen Q D, Shah S M. et al . Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a phase I clinical trial.  Hum Gene Ther. 2006;  17 (2) 167-176
    Google Scholar
  • 11 Juan de E, Machemer Jr R. Vitreous surgery for hemorrhagic and fibrous complications of age- related macular degeneration.  Am J Ophthalmol. 1988;  105 (1) 25-29
    Google Scholar
  • 12 Del Priore L V, Kuo Y H, Tezel T H. Age-related changes in human RPE cell density and apoptosis proportion in situ.  Invest Ophthalmol Vis Sci. 2002;  43 (10) 3312-3318
    Google Scholar
  • 13 Eckardt C, Eckardt U. Macular translocation in nonexudative age-related macular degeneration.  Retina. 2002;  22 (6) 786-794
    Google Scholar
  • 14 Eckardt C, Eckardt U, Conrad H G. Macular rotation with and without counter-rotation of the globe in patients with age-related macular degeneration.  Graefes Arch Clin Exp Ophthalmol. 1999;  237 (4) 313-325
    Google Scholar
  • 15 Gelisken F, Voelker M, Schwabe R. et al . Full macular translocation versus photodynamic therapy with verteporfin in the treatment of neovascular age-related macular degeneration: 1-year results of a prospective, controlled, randomised pilot trial (FMT-PDT).  Graefes Arch Clin Exp Ophthalmol. 2007;  245 (8) 1085-1095
    Google Scholar
  • 16 Hawkins B S, Bressler N M, Miskala P H. et al . Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: ophthalmic findings: SST report no. 11.  Ophthalmology. 2004;  111 (11) 1967-1980
    Google Scholar
  • 17 Joussen A M, Heussen F M, Joeres S. et al . Autologous translocation of the choroid and retinal pigment epithelium in age-related macular degeneration.  Am J Ophthalmol. 2006;  142 (1) 17-30
    Google Scholar
  • 18 Joussen A M, Joeres S, Fawzy N. et al . Autologous translocation of the choroid and retinal pigment epithelium in patients with geographic atrophy.  Ophthalmology. 2007;  114 (3) 551-560
    Google Scholar
  • 19 Kano T, Abe T, Tomita H. et al . Protective effect against ischemia and light damage of iris pigment epithelial cells transfected with the BDNF gene.  Invest Ophthalmol Vis Sci. 2002;  43 (12) 3744-3753
    Google Scholar
  • 20 Khurana R N, Fujii G Y, Walsh A C. et al . Rapid recurrence of geographic atrophy after full macular translocation for nonexudative age-related macular degeneration.  Ophthalmology. 2005;  112 (9) 1586-1591
    Google Scholar
  • 21 Lappas A, Foerster A M, Weinberger A W. et al . Translocation of iris pigment epithelium in patients with exudative age-related macular degeneration: long-term results.  Graefes Arch Clin Exp Ophthalmol. 2004;  242 (8) 638-647
    Google Scholar
  • 22 MacLaren R E, Uppal G S, Balaggan K S. et al . Autologous transplantation of the retinal pigment epithelium and choroid in the treatment of neovascular age-related macular degeneration.  Ophthalmology. 2007;  114 (3) 561-570
    Google Scholar
  • 23 Mruthyunjaya P, Stinnett S S, Toth C A. Change in visual function after macular translocation with 360 degrees retinectomy for neovascular age-related macular degeneration.  Ophthalmology. 2004;  111 (9) 1715-1724
    Google Scholar
  • 24 Rosenfeld P J, Brown D M, Heier J S. et al . Ranibizumab for neovascular age-related macular degeneration.  N Engl J Med. 2006;  355 (14) 1419-1431
    Google Scholar
  • 25 Semkova I, Kreppel F, Welsandt G. et al . Autologous transplantation of genetically modified iris pigment epithelial cells: a promising concept for the treatment of age-related macular degeneration and other disorders of the eye.  Proc Natl Acad Sci U S A. 2002;  99 (20) 13 090-13 095
    Google Scholar
  • 26 Steinhorst U H, Kuster S. Surgical treatment of senile macular degeneration: rotation or transplantation?.  Klin Monatsbl Augenheilkd. 1997;  210 (4) aA1-aA2
    Google Scholar
  • 27 Szurman P, Roters S, Grisanti S. et al . Ultrastructural changes after artificial retinal detachment with modified retinal adhesion.  Invest Ophthalmol Vis Sci. 2006;  47 (11) 4983-4989
    Google Scholar
  • 28 Thumann G, Aisenbrey S, Schaefer F. et al . Instrumentation and technique for delivery of tissue explants to the subretinal space.  Ophthalmologica. 2006;  220 (3) 170-173
    Google Scholar
  • 29 Thumann G, Aisenbrey S, Schraermeyer U. et al . Transplantation of autologous iris pigment epithelium after removal of choroidal neovascular membranes.  Arch Ophthalmol. 2000;  118 (10) 1350-1355
    Google Scholar
  • 30 Toth C A, Freedman S F. Macular translocation with 360-degree peripheral retinectomy impact of technique and surgical experience on visual outcomes.  Retina. 2001;  21 (4) 293-303
    Google Scholar
  • 31 Treumer F, Bunse A, Klatt C. et al . Autologous retinal pigment epithelium-choroid sheet transplantation in age related macular degeneration: morphological and functional results.  Br J Ophthalmol. 2007;  91 (3) 349-353
    Google Scholar
  • 32 Meurs J C, ter Averst van E, Hofland L J. et al . Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes.  Br J Ophthalmol. 2004;  88 (1) 110-113
    Google Scholar
  • 33 Wolf S, Lappas A, Weinberger A W. et al . Macular translocation for surgical management of subfoveal choroidal neovascularizations in patients with AMD: first results.  Graefes Arch Clin Exp Ophthalmol. 1999;  237 (1) 51-57
    Google Scholar

Prof. Gabriele Thumann

IZKF Biomat, RWTH Aachen

Pauwelsstr. 30

52074 Aachen

Phone: ++ 49/2 41/8 03 57 28

Fax: ++ 49/2 21/9 40 29 23

Email: Gthumann@ukaachen.de

      >