Grant: Operating Grant

Blindness is a dreaded condition that costs Canada $15.8 billion annually. Age related macular degeneration (ARMD) is the leading cause of blindness in our country. In severe cases of ARMD, abnormal blood vessels grow beneath and within the retina, causing damage to important cells responsible for vision. Vascular Endothelial Growth Factor (VEGF) plays an important role in the growth of these pathologic vessels. The development of drugs that inhibit VEGF has revolutionized the treatment of ARMD. Our first study showed that uptake and diffusion of these therapies has been very rapid, and has involved the use of both off-label bevacizumab and the approved drug, ranibizumab. However, VEGF has a wide array of functions in physiologic processes, raising concerns about the potential for adverse events occurring as a result of pharmacologic inhibition of this signaling molecule. In fact, intravenous administration of bevacizumab has already been associated with an increased risk of stroke and other adverse vascular effects, and a recent meta-analysis has suggested an increased risk of stroke in patients receiving ranibizumab injections for ARMD. Further, because VEGF inhibitors are delivered into the eye via serial injections, this therapy may also lead to potentially blinding ocular complications including retinal detachment. The goal of this proposal is to assess the risks of adverse vascular and ocular events associated with the rapid uptake of VEGF inhibitor therapies for ARMD. Over a very short period, providing VEGF inhibitors for ARMD has become a very common clinical service, and has become one of the costliest programs for publicly funded drug plans in Canada. Our results will not only provide important safety information to help guide clinical care, but will also inform evidence-based policy decisions in these ambitious public drug programs and beyond.