Synergies of VEGF inhibition and photodynamic therapy in the treatment of age-related macular degeneration.
OBJECTIVE
Photodynamic therapy (PDT) and the administration of compounds acting against vascular endothelial growth factor (anti-VEGF) are approved for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Experimental evidence that the combined use of both treatment options may improve therapeutic outcome is presented.


METHODS
Fertilized chick eggs were incubated until day 12 of embryo development (EDD12) and were treated by PDT using two different photosensitizing agents (liposomal formulation of BPD-MA; m-THPP encapsulated in polymeric nanoparticles) and were visualized using an epifluorescence microscope. Vascular occlusion of the treated zones of the chorioallantoic membrane (CAM) was assessed by fluorescence angiography 24 and 48 hours after treatment. Alternatively, PDT-treated areas were exposed to a soluble VEGF receptor antagonist (sFlt-1) 6 hours after treatment and were analyzed.


RESULTS
Vascular occlusion in the PDT-treated areas was observed with both photosensitizers 24 hours after treatment. Reperfusion of preexisting blood vessels and first signs of revascularization were visible 48 hours after PDT. Topical administration of sFlt-1 to the treated areas augmented occlusion and limited subsequent angiogenesis in a dose-dependent manner.


CONCLUSIONS
The combined use of PDT and of agents targeting angiogenic cytokines may synergistically improve therapeutic outcome after combined treatment in patients with CNV secondary to AMD.
Zuluaga
Maria-Fernanda
MF
Laboratory of Pharmaceutics and Biopharmaceutics, Section of Pharmaceutical Sciences, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva, Switzerland.
Mailhos
Carolina
C
Robinson
Gregory
G
Shima
David T
DT
Gurny
Robert
R
Lange
Norbert
N
D000818:Animals; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005451:Fluorescein Angiography; D006801:Humans; D008081:Liposomes; D008268:Macular Degeneration / Q000188:drug therapy*; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000627:therapeutic use*; D000077362:Verteporfin
D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C481734:meso-tetra-(4-hydroxyphenyl)porphyrin; D000077362:Verteporfin; D040281:Vascular Endothelial Growth Factor Receptor-1