Chancen und Risiken der Anti-VEGF-Therapie

Zusammenfassung

Der vascular endothelial growth factor (VEGF) besitzt eine Schlüsselrolle für die Regulation der Angiogenese. Weil der pluripotente Faktor aber auch physiologische Abläufe wie Hämodynamik, Hämatopoese, Immunabwehr, Hormonfreisetzung und Wundheilung beeinflusst, müssen mögliche Interaktionen einer medikamentösen Hemmung berücksichtigt werden. Die Erfahrungen mit der höher dosierten, intravenösen Gabe des Vollantikörpers Bevacizumab (Avastin®) haben das Augenmerk auf mögliche Nebenwirkungen durch eine vollständige VEGF-Blockade gelenkt. Bisherige Daten deuten darauf hin, dass selbst nach intravitrealer Injektion eine systemische Exposition erreicht wird, die zu messbaren Effekten führen kann. Eine Veränderung relevanter Kreislaufparameter könnte eine direkte Beeinflussung der Morbidität bewirken. Obwohl vorerst keine drastischen Auswirkungen beobachtet wurden, lassen die bisherigen Studien keine sichere Beurteilung von Signifikanz und Relevanz zu. Eine VEGF-Blockade kann den Tonus und die Autoregulation der Netzhautgefäße verändern. Die physiologische Fenestrierung der choroidalen Aderhautgefäße zeigte sich im Tiermodell signifikant reduziert. Mögliche Auswirkungen auf die lokale Sauerstoffversorgung in ischämischen Netzhautarealen (Gefäßverschlüsse) können für den klinischen Alltag nicht ausgeschlossen werden. In der Therapie retinaler Neovaskularisationen versprechen die VEGF-Inhibitoren allerdings gegenüber destruktiven Therapieverfahren (Laserkoagulation, Kryogulation) ein schnelles Ansprechen und weiteren Funktionserhalt (Gesichtsfeld). Die Ausreifung neovaskulärer Gefäße (Perizyten) und die sekundäre Formation von Membranen limitiert den Zeitpunkt, zu dem eine medikamentöse Behandlung indiziert ist.

Abstract

Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. Through regulation of haemodynamics, haematopoesis and the immune system, endocrinology and reparative processes, inhibition of VEGF can cause multiple adverse events. Previous data suggest that – even after intravitreal injection – systemic exposure might occur, thus bearing the risk of manifestation of side effects. Experience with intravenous administration of the antibody bevacizumab (Avastin®) pointed to the potential consequences of a pan-VEGF blockade. The change of haemodynamic parameters implies a potential influence on the patient’s morbidity. Studies already conducted during the approval process do not provide sufficient statistical power when evaluating whether systemic events significantly differ between the treatment and control groups. Retinal perfusion showed an altered vascular tone (change in vessel diameter) following anti-VEGF treatment. Physiological fenestration of the choroicapillaris is significantly reduced. Possible effects on the local oxygen supply in ischaemic tissue have to be considered. In contrast to destructive treatment modalities (laser, cryo), VEGF inhibitors promise the prompt and efficient response of retinal neovascularisation and the preservation of a better function (visual fields). The maturation of growing vessels (pericytes) and the secondary formation of membranes are limiting factors with regard to the time-point at which anti-VEGF therapy is most effective. A diligent use of the available drugs has to take into account which types of exudative retinopathy are showing no or only very limited response to the treatment.

Schlüsselwörter

Retina - VEGF - Thrombembolie - Schlaganfall - Bevacizumab (Avastin) - Nebenwirkungen

Key words

retina - VEGF - thromboembolism - stroke - bevacizumab (Avastin) - side effects

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