Ranibizumab e Bevacizumab sono i due principi attivi dei farmaci Lucentis e Avastin impiegati ormai di routine nel trattamento delle neovascolarizzazioni oculari e, in particolare, nel trattamento della maculopatia senile di tipo essudativo (umida).
Scopo dello studio è valutare gli effetti dei 2 farmaci in un modello animale sperimentale nel quale si è ottenuta la produzione di VEGF con conseguente sviluppo di neovascolarizzazione sottoretinica.
L’esito della sperimentazione ha mostrato che l’iniezione di bevacizumab e ranibizumab si sono dimostrate entrambe efficaci nel determinare la soppressione della neovascolarizzazione, anche se per il bevacizumab tale soppressione si è dimostrata più duratura. In particolare si è ottenuta la soppressione anche nell’occhio controlaterale, indicando come per il bevacizumab occorra considerare una diffusione con un verosimile conseguente effetto sistemico a lungo termine.
Per il ranibizumab non si è avuta alcuna diffusione sistemica.



American Academy of Ophthalmology Journal
Effects of Intraocular Ranibizumab and Bevacizumab in Transgenic Mice Expressing Human Vascular Endothelial Growth Factor

Miki K, Miki A, Matsuoka M, Muramatsu D, et al.

Ophthalmology
September 2009, Volume 116, Issue 9, Pages 1748–1754



Objective This study compared the effects of intraocular injections of ranibizumab (RBZ) and bevacizumab (BVZ) in transgenic mouse models in which human vascular endothelial growth factor (VEGF) causes subretinal neovascularization (NV) or exudative retinal detachment.

Design Randomized trials in animal models.

Participants Transgenic mice in which the rhodopsin promoter drives expression of human VEGF in photoreceptors (rho/VEGF mice) and double transgenic mice with doxycycline-inducible expression of human VEGF in photoreceptors (Tet/opsin/VEGF mice).

Methods Rho/VEGF mice received intraocular injections of RBZ, BVZ, or vehicle, and after various time periods the area of subretinal NV was measured. Tet/opsin/VEGF mice were given an intraocular injection of RBZ, BVZ, or vehicle, and after 5 days of doxycycline treatment the presence or absence of retinal detachment was determined.

Main Outcome Measures Area of subretinal NV per retina in rho/VEGF mice and the occurrence of retinal detachment in Tet/opsin/VEGF mice.

Results In rho/VEGF mice, intraocular injections of RBZ or BVZ strongly suppressed subretinal NV, but the duration of effect was greater for BVZ. Three injections of 10 μg of BVZ over the course of 2 weeks not only suppressed subretinal NV in the injected eye but also caused significant suppression in the fellow eye, indicating a systemic effect. In doxycycline-treated Tet/opsin/VEGF mice, intraocular injection of 10 μg of BVZ significantly reduced the incidence of exudative retinal detachment compared with injection of 10 μg of RBZ. Injection of 25 μg of BVZ reduced the incidence of retinal detachment in both eyes.

Conclusions Intraocular injections of RBZ and BVZ had similar efficacy in rho/VEGF mice, but the duration of effect was greater for BVZ. In Tet/opsin/VEGF mice, in which expression levels of human VEGF are very high and the phenotype is severe, BVZ showed greater efficacy than RBZ. In both models, higher doses or repeated injections of BVZ, but not RBZ, resulted in a systemic effect. These data suggest that BVZ is not inferior to RBZ for treatment of subretinal NV in mice and is superior in a severe model. The systemic effects of BVZ after intraocular injection deserve further study and consideration of their potential consequences.

Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.