Extrapolating anti-vascular endothelial growth factor therapy into pediatric ophthalmology: Promise and concern

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T he use of anti-vascular endothelial growth factor (VEGF) agents has dramatically changed the way we treat many retinal diseases. This paradigm shift in treatment is due to the ability of these drugs to inhibit VEGF, a molecule that has a pivotal role in a large variety of retinal conditions, including age-related macular degeneration (AMD), proliferative diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity (ROP), and many forms of retinal edema. Intravitreal ranibizumab (Lucentis; Genentech, San Francisco, CA) is currently FDA approved for the treatment of neovascular AMD. Prior to ranibizumab’s approval, bevacizumab (Avastin; Genentech), a larger antibody approved for the treatment of colon cancer, achieved widespread off-label intravitreal use in ophthalmology. The phenomenal speed with which bevacizumab use was adopted was due to a variety of reasons: there was an unmet need in the treatment of AMD and bevacizumab worked much better than approved drugs; it was inexpensive and available; and from a molecular standpoint, it was very similar to ranibizumab, which had just completed several large randomized clinical trials with outstanding results—but was not yet approved. After ranibizumab received FDA approval for neovascular AMD, bevacizumab maintained a significant share of the market for AMD due to its much lower cost than ranibizumab, and for non-AMD indications, it is used much more frequently than ranibizumab. Despite the similarities between these 2 drugs, there are significant differences. Bevacizumab is a full-length antibody, and ranibizumab is a modified Fab fragment that is ⁄3 the size of bevacizumab. Once the drug reaches the bloodstream, bevacizumab has a dramatically longer half-life than ranibizumab. Despite ranibizumab’s shorter systemic half-life, concern of systemic risk was raised during an interim analysis of almost 2400 AMD patients in the SAILOR (Safety Assessment of Intravitreal Lucentis for AMD) trial.