Complete blood vessel occlusion is required for the treatment of age-related macular degeneration (AMD). AMD is the leading cause of blindness in developed countries and current treatment regimes have potential to cause collateral damage, or do not remove pre-existing unwanted vasculature. It has been proposed that two-photon excitation (TPE) photodynamic therapy (PDT) can be applied to cause local blood vessel occlusion without damaging surrounding retinal tissues. The in ovo chicken chorioallantoic membrane (CAM) is used as the model for vascularization in the wet form of AMD; novel techniques for the utilization of the CAM are reported. Complete occlusion of CAM vessels ~15 μm in diameter is achieved using the clinically approved photosensitizer Verteporfin (Visudyne®, QLT, Incorporated, Vancouver, British Columbia, Canada) and TPE activation. The average and peak irradiances used for treatment are 3.3×106 W/cm2 and 3.7×1011 W/cm2, respectively. A total fluence of 1.1×108 J/cm2 is the dosage required for successful occlusion, and it is expected that for optimal conditions it will be much less. These results are the first proof-of-principle evidence in the literature that indicate TPE-PDT can be used to occlude small blood vessels. Further investigation will help determine the utility of TPE-PDT for treating wet AMD, perhaps through targeting feeder vessels.