PerspectiveSafety Implications of Vascular Endothelial Growth Factor Blockade for Subjects Receiving Intravitreal Anti–Vascular Endothelial Growth Factor Therapies
Section snippets
Route of Administration of Anti–Vascular Endothelial Growth Factor Agents and Systemic Safety
The route of administration must be considered to understand potential systemic effects of anti-VEGF agents used to treat neovascular AMD. Interestingly, intraocular drugs also have been found in the systemic circulation, despite the presence of the blood-ocular barrier (ie, blood-retinal barrier), which shields the retina from circulating blood.5 Ocular drugs that are injected into the eye may enter the systemic circulation after absorption through uveal vessels (iris or ciliary body) or by
Systemic Safety of Systemically Administered Anti–Vascular Endothelial Growth Factor Agents
Systemic AEs with VEGF isoform inhibition must be considered because of the ubiquitous distribution of the molecule and because VEGF isoform levels can change in response to disease conditions. It is possible that patients with lower systemic levels of VEGF-A have lower thresholds of tolerance to anti-VEGF agents and are at higher risk for systemic AEs that result directly from VEGF inhibition. To gain an understanding of potential systemic AEs that may emerge with intravitreal administration
Pegaptanib Sodium
Pegaptanib sodium is a 28-base ribonucleic aptamer that binds with high affinity to VEGF165 and larger isoforms. In the phase 3 VEGF Inhibition Study in Ocular Neovascularization (VISION) clinical trial, intravitreal pegaptanib sodium was well tolerated. Serious ocular AEs associated with pegaptanib sodium in the first year of the VISION were endophthalmitis, traumatic cataract, and retinal detachment, which were attributed to the injection preparation or procedure rather than to the drug
Mechanisms for Identifying Low Rate Systemic Safety Signals
It is useful to interpret trial-generated safety profiles to help predict AE risk for real-life patients. Notably, however, safety profiles of marketed drugs used in the real-life setting may differ from those anticipated based on clinical trial data because extremely rare AEs may be undetected during clinical trials.
Even large-scale clinical trials, including the MARINA (n = 716), ANCHOR (n = 423), SAILOR (n = 4,300), and the ongoing CATT (n = 1,200) and VIEW 1 (n = 1,200) and VIEW 2 (n =
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