Pharmakologische Vitreolyse

 

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Zusammenfassung

Hintergrund: Der Glaskörper hat entscheidenden Einfluss auf die Entwicklung und den Verlauf der meisten vitreoretinalen Erkrankungen, welche heute mittels Vitrektomie behandelt werden. Da die mechanische Vitrektomie unvollständig ist, sucht man nach pharmakologischen, enzymatischen Alternativen, welche die Intervention sicherer und effektiver machen sollen. Methode: Verschiedene Substanzen (Chondroitinase, Dispase, Hyaluronidase, Plasmin, Microplasmin) wurden präklinisch und im Falle von Hyaluronidase und Microplasmin (ThromboGenics Ltd., Dublin, Leuven) auch klinisch untersucht. Die bislang veröffentlichten präklinischen und klinischen Ergebnisse werden berichtet. Resultate: Microplasmin kann dosisabhängig eine komplette hintere Glaskörperabhebung induzieren. Morphologische, immunzytochemische oder funktionelle Netzhautveränderungen finden sich nicht. Die zwei bislang veröffentlichten Phase-II-Studien bestätigen dieses Wirkprofil bei guter Verträglichkeit. Die übrigen getesteten Substanzen scheinen weniger gut zur pharmakologischen Vitreolyse geeignet zu sein, da sie Netzhautschäden induzieren können (Dispase) oder den Glaskörper nur verflüssigen, ohne ihn primär von der Netzhaut abzulösen (Hyaluronidase). Schlussfolgerung: Microplasmin trennt den Glaskörper von der Netzhaut ohne morphologische oder funktionelle Netzhautveränderungen zu induzieren. Die Ergebnisse der klinischen Prüfung lassen erkennen, dass Microplasmin hilfreich sein kann, die Ablösung des Glaskörpers vor oder bei der Vitrektomie zu erleichtern und die Intervention atraumatischer und sicherer zu machen.

Abstract

Background: The vitreous plays an important role in the development and progression of vitreoretinal diseases. Vitrectomy is the treatment modality of choice in these cases. However, mechanical vitrectomy is incomplete. Therefore, alternative strategies have been pursued including pharmacological means such as enzymes. The goal of pharmacological vitreolysis is to make the surgical intervention easier and less traumatic. Methods: Different substances have been investigated, including chondroitinase, dispase, hyaluronidase, plasmin, and microplasmin. Besides preclinical investigations, hyaluronidase and microplasmin (ThromboGenics Ltd., Dublin, Leuven) have been tested clinically. Results from the literature are reported herein. Results: Plasmin and microplasmin are both capable of inducing posterior vitreous detachment (PVD) in a dose- and time-dependent manner. There are no morphological or functional changes of the retina at therapeutic doses. Two phase II studies published to date demonstrate both efficacy and safety. Phase III studies are ongoing, and results are expected during 2010. Other enzymes tested show limitations in that retinal damage may occur (dispase) or liquefaction (hyaluronidase) occurs without cleavage of the vitreous cortex from the retina. Conclusions: Microplasmin induces PVD. Results from clinical trials show that microplasmin helps to detach the vitreous cortex from the retina. This may be advantageous in terms of complete vitreous removal and less traumatic intervention compared to mechanical techniques, such as vitrectomy and peeling of the internal limiting membrane.

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Prof. Dr. Arnd Gandorfer

Augenklinik der Ludwig-Maximilians-Universität München

Mathildenstr. 8

80336 München

Phone: ++ 49/89/51 60 38 56

Fax: ++ 49/89/51 60 47 78

Email: arnd.gandorfer@med.uni-muenchen.de