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.
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