Systemic and ocular safety of intravitreal anti-VEGF therapies for ocular neovascular disease.

The treatment of ocular neovascular diseases is being revolutionized by intravitreal therapies targeting vascular endothelial growth factor (VEGF). Two agents are approved for treating neovascular age-related macular degeneration and are being evaluated for other retinal conditions: the RNA aptamer pegaptanib and the monoclonal antibody antigen-binding fragment ranibizumab. Bevacizumab, a related antibody, is being used similarly, although its use is off-label. Pegaptanib selectively binds to a VEGF isoform identified as being especially pathogenic in the eye and spares other isoforms, whereas the other two agents nonselectively bind all VEGF isoforms. Because VEGF is involved in a wide variety of physiologic processes, the ocular and systemic safety of anti-VEGF agents is of paramount concern. I provide an overview of safety data for intravitreal anti-VEGF therapies, focusing primarily on randomized, controlled trials. For pegaptanib, an accumulation of data from pivotal trials and a dedicated systemic safety study have revealed no ocular or systemic safety concerns. For ranibizumab, the principal ocular adverse event detected in clinical trials was a low frequency of ocular inflammation, and systemic adverse events included a slightly elevated risk of nonocular hemorrhage and stroke. Safety data from properly designed randomized controlled trials for bevacizumab are not available.