Gibt es eine medikamentöse Therapie der altersbedingten Makuladegeneration? - Derzeitiger Stand und neue therapeutische Ansätze

Zusammenfassung

Die altersbedingte Makuladegeneration (AMD), in der westlichen Welt eine der führenden Ursachen für Erblindungen (im Sinne des Gesetzes) im höheren Alter, wird unterteilt in eine häufigere (ca. 85 % der Fälle) trockene und eine feuchte Form. Alterungsprozesse führen bei der trockenen AMD zu Ablagerungen von zellulären Abbauprodukten im Bereich des retinalen Pigmentepithels und der Bruch’schen Membran mit der Folge degenerativer Veränderungen. Die chorioidale Neovaskularisation (CNV) verursacht bei der feuchten AMD eine rasch progrediente Minderung des zentralen Sehvermögens. Komplexe Prozesse wie Hypoxie und/oder Entzündungsreaktionen führen über eine erhöhte Expression von angiogenen Signalmolekülen zur Entstehung einer CNV. Dabei erscheint vor allem die Ausschüttung des vaskulären endothelialen Wachstumsfaktors (vascular endothelial growth factor [VEGF]) eine besondere Rolle zu spielen. Verschiedene monotherapeutische Ansätze wie photodynamische Therapie oder die intravitreale Gabe von VEGF-Inhibitoren sind mittlerweile zugelassen oder befinden sich im Endstadium der klinischen Erprobung. Die klinischen Ergebnisse bzw. die Notwendigkeit häufiger Behandlungen lassen eine Monotherapie langfristig als nichtpraktikabel erscheinen. Der Fokus zukünftiger Entwicklungen wird daher in Analogie zur Onkologie auf der Untersuchung von Kombinationsstrategien liegen, die sowohl die Pathogenese der Erkrankung wie auch Begleiteffekte der einzelnen Therapieansätze berücksichtigen müssen.

Abstract

Age-related macular degeneration (AMD) is the major cause of legal blindness in society today. In dry AMD age-related changes in Bruch’s membrane and RPE result in the accumulation of cell debris with consequent degeneration. In the less common but more aggressive form, wet AMD, hypoxia and inflammation lead to an up-regulation of different growth factors such as VEGF resulting in formation of choroidal neovascularisation. Different therapeutic modalities have evolved to address this problem. Examples are photodynamic therapy to eradicate choroidal neovascularisation (CNV) via a physiochemical reaction or intravitreal application of anti-VEGF agents to stop leakage of fluid from the same CNV. The overall results have been either disappointing or not practical because of the necessity of chronic treatment. The treatment goal continues to evolve to that already realised in oncology which is for a cure. This mandates the investigation of combination strategies. Combination strategies should focus on utilising the differing mechanisms of action on the pathogenesis of the disease all the while minimising the side effects of the individual therapeutic agents.

AMD - Zytokine - Kombinationstherapie

AMD - cytokines - combination therapy

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