Zusammenfassung
Hintergrund
Zu den lokalen Langzeitschäden der anti-VEGF-Therapie ist die Datenlage unübersichtlich. Ziel der vorliegenden Übersicht ist es deshalb, die pathophysiologischen Grundlagen für Entwicklung und Fortschreiten der Makula-Atrophie (MA) und des möglichen Einflusses einer anti-VEGF-Therapie auf den Verlauf plausibel zu machen.
Methoden
Die Übersicht basiert auf einer Literaturrecherche in PubMed mit den Schlüsselwörtern „wet AMD“ und „macular atrophy“ (151 Treffer). Unter den seit Anfang 2013 erschienenen Publikationen (n = 90) wurden diejenigen ausgeschieden, die auf Diagnostik und Verlauf, aber nicht Therapie ausgerichtet waren. Unter dem Begriff MA wird hier die Atrophie des funktionell relevanten Komplexes von Photorezeptoren, retinalem Pigmentepithel (RPE), Bruch-Membran und Choriokapillaris verstanden.
Ergebnisse
Experimentell führt eine primäre, vollständige VEGF-Suppression zu erheblichen Veränderungen in der Choriokapillaris, eine inkomplette VEGF-Suppression hingegen zum schleichenden Untergang von Ganglienzellen und Photorezeptoren. Klinisch sind allerdings oft bereits vor Therapiebeginn degenerative Veränderungen an RPE und Bruch-Membran vorhanden. Folglich ist die MA Folge der fortschreitenden neurodegenerativen Grunderkrankung zu verstehen, die vermutlich durch die anti-VEGF-Therapie beschleunigt wird. Unter Ranibizumab ist ein rascheres Fortschreiten zu erwarten als unter Bevacizumab sowie unter monatlicher Therapie rascher als unter PRN-Therapie (lat. pro renata, dt. nach Bedarf). Trotz der dadurch induzierten MA ist die retinale Funktion unter konsequenter Therapie besser, sodass die Beschleunigung der Progression unter anti-VEGF-Therapie in den ersten 5 Jahren nur bei primär fortgeschrittener MA Bedeutung gewinnt.
Schlussfolgerung
Trotz der Zweifel an der langfristigen Sicherheit der anti-VEGF-Therapie ist aus Sicht des Autors eine konsequente Therapie zur Erhaltung der Sehfunktion verhältnismäßig. Dabei lässt sich der therapieinduzierte Schaden kaum von dem natürlichen Fortschreiten der AMD und der biologischen Situation der Patienten trennen.
Abstract
Background
Current understanding of the mechanisms that underlie the long-term consequences of anti-VEGF therapy in wet, age-related macular degeneration (AMD) is poor. Here, the impact of this treatment on the development of macular atrophy (MA) is discussed based on our current pathophysiological understanding.
Methods
This review is based on a PubMed literature survey using the MeSH terms “wet AMD” and “macular atrophy” (151 hits) and limited to publications since 2013 (n = 90). Publications focussing on diagnostics and clinical course not in the context of therapy were excluded. Macular atrophy is defined herein as atrophy affecting the functionally relevant complex of photoreceptors, retinal pigmented epithelium (RPE), Bruch’s membrane and choriocapillaris.
Results
Experimentally, a primary complete suppression of local VEGF leads to evident changes in the choriocapillaris, whereas its incomplete suppression exacerbates cell death of RPE and photoreceptors. Since pre-existing atrophic changes are already present at diagnosis, the role of anti-VEGF treatment cannot be separated from the spontaneous progression of AMD. The progression of MA appears to be faster under ranibizumab than bevacizumab, and likewise on a monthly rather than as-needed basis. Although MA progresses more rapidly under consequent therapy, visual function remains better. Hence, a functionally relevant progression of atrophy during the first five years of treatment would only be expected in pre-existing advanced MA.
Conclusions
Despite doubts regarding the long-term safety of anti-VEGF therapy, it is the author’s view that this is the only option to stabilise visual function. The impact of therapy-induced damage on the spontaneous progression of AMD and the biological status of the aging individual cannot be unequivocally assessed.
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J.G. Garweg erhält Beraterhonorare für verschiedene pharmazeutische Konzerne (Alcon, Allergan, Novartis, Bayer) und nimmt als Principal Investigator an verschiedenen internationalen und nationalen, teils durch die Pharmaindustrie gesponsorten Studien teil. Die hier präsentierten Daten haben nichts mit dieser Tätigkeit zu tun.
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Die Ergebnisse wurden als Präsentation auf dem DOG-Kongress 2015 in Berlin präsentiert.
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Garweg, J.G. Makula-Atrophie bei feuchter altersabhängiger Makuladegeneration. Ophthalmologe 113, 1036–1045 (2016). https://doi.org/10.1007/s00347-016-0306-9
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DOI: https://doi.org/10.1007/s00347-016-0306-9
Schlüsselwörter
- Choroidale Neovaskularisation
- Retinales Pigmentepithel
- Bruch-Membran
- Choriokapillaris
- Geografische Atrophie