Understanding anti-vascular endothelial growth factor medications: chemical properties, costs, and side effects

Vascular endothelial growth factor (VEGF) is an important driver of abnormal retinal neovascularization and increased vascular permeability. VEGF overexpression is associated with a number of retinal conditions, such as diabetic macular edema (DME), and neovascular age-related macular degeneration (nAMD). Anti-VEGF treatments have been the most common for these conditions and have improved vision by reducing abnormal blood vessel formation and leakage. This narrative review addressed the fact that the pharmacological properties, safety profiles, and cost-effectiveness of the currently marketed anti-VEGF intravitreal agents (i.e. bevacizumab, ranibizumab, aflibercept, brolucizumab, pegaptanib, and recently faricimab) differ and therefore, each of these agents, have their own unique molecular structure, target specificity, duration of action in the eye, and systemic circulation, each of which will affect the dosing intervals and treatment burden as well as the safety and adverse events associated with each drug. Aflibercept is a high-binding-affinity decoy receptor and is therefore distinct from faricimab, which is a dual-action (VEGF-A and angiopoietin-2) inhibitor. By contrast, ranibizumab, bevacizumab, brolucizumab, and pegaptanib are anti-angiogenic agents with different VEGF blockade profiles, which ultimately lead to distinct clinical outcomes and pharmacokinetic profiles. While anti-VEGF therapies are highly effective, the outcomes regarding safety, efficacy, and cost depend heavily on the study design and reflect the actual treatment paradigm and continuum of care within the healthcare system. The various attributes of agents should help personalize a patient's treatment approach while also addressing potential challenges related to the safety, efficacy, and longevity of treatment for retinal diseases.