Synergies of VEGF inhibition and photodynamic therapy in the treatment of age-related macular degeneration.

PURPOSE

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.