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H. van den Bergh, G. Wagnieres, E. Debefve, B. Pegaz, J.-P. Ballini; Video Monitoring of Neovessel Occlusion Induced by Photodynamic Therapy in Combination With Anti-VEGF Therapy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2721.
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Combining angioocclusive verteporfin with anti-VEGF agents may lead to synergistic effects and better outcomes than either agent alone in treating choroidal neovascularization. These potential benefits have led to interest in efficient in vivo screening procedures. The aim of this work is to monitor angioocclusion with verteporfin in combination with an anti-VEGF agent, ranibizumab in capillary vessels, and to record events in real-time using a high-sensitivity video camera.
A procedure was developed based on intravenous injection of photosensitizers and fluorescent dyes into the chick chorioallantoic membrane (CAM), combined with the topical application of an anti-VEGF agent to the CAM surface. Real-time angioocclusion was recorded using a Peltier-cooled CCD camera.
Vessel occlusion in the CAM model was reproducible and similar to that observed in clinical use of verteporfin. Real-time video recording permitted monitoring of platelet aggregation and revealed selective vascular closure. Platelets accumulated at intracellular junctions within seconds after verteporfin activation. A stabilized plug formed and capillaries were completely closed 15 minutes after activation. Larger-diameter vessels remained patent. Evaluation with an ultra-high-sensitivity camera revealed occlusion of the treated area after 5 minutes with doses of verteporfin and light similar to those used clinically. Topical application of anti-VEGF after verteporfin PDT prevents the reperfusion of occluded vessels.
Real-time video recording of neovessel thrombosis using the CAM model and verteporfin permitted monitoring of the location, aggregation and release of platelets, and revealed selective vascular closure. These results suggest that ultra-high-sensitivity video cameras permit real-time monitoring of angioocclusion under conditions similar to clinical settings. Evidence of a synergy between verteporfin therapy and anti-VEGF agent, ranibizumab has been demonstrated.
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