Intravitreal anti-VEGF agents and cardiovascular risk

Antagonists of Vascular Endothelial Growth Factor (Anti-VEGF) are widely administered by intravitreal injection for the treatment of ocular pathologies such as Age-related Macular Degeneration, Diabetic Macular Edema, Proliferative Diabetic Retinopathy and occlusion of retinal vessels. Anti-VEGF agents, in particular bevacizumab, were introduced in oncology to inhibit tumor-induced angiogenesis feeding neoplastic tissues. Subsequently, other specific agents were developed for intraocular administration. Whereas systemic administration of anti-VEGF agents in oncology is burdened by increased risk of arterial hypertension and embolism, agents administered for ophthalmic indications are delivered locally into the eye globe in much smaller quantities. Nevertheless, clinical observations have raised the possibility that, even in these conditions, anti-VEGF agents may increase cardiovascular risk in patients who, being elderly and/or diabetic, are intrinsically prone to such events. This paper aims at reviewing the current knowledge on VEGF and its pharmacologic antagonists from mechanistic and side effect points of view, with specific reference to patients with sight-threatening conditions. Internists should be aware of the need to collaborate with ophthalmologists and pharmacovigilance operators to define as best as possible the risk/benefit balance of intravitreal agents in patients who might lose their sight if left untreated, or increase their risk of suffering a cardiovascular event if treated.