Systemic Effects of Intravitreal Anti-VEGF Therapy: A Review of Safety across Organ Systems

Abstract

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies have transformed the management of retinal diseases such as diabetic macular edema and neovascular age-related macular degeneration. However, concerns about their systemic absorption and potential adverse effects on overall health remain. In this review, we systematically aggregate existing literature on the systemic impact of anti-VEGF therapy, with a detailed analysis of the pharmacodynamics and pharmacokinetics of individual drugs. By examining their metabolism, clearance, and systemic exposure, we aim to clarify the extent of their effects beyond the eye. We further explore their influence on renal and cardiovascular health, with evidence suggesting a generally safe profile in the short term but potential risks in high-risk patients, particularly those with preexisting kidney or heart conditions. Additionally, this review addresses the critical concerns surrounding anti-VEGF use in special populations, including pregnant and lactating women and neonates with retinopathy of prematurity (ROP). We discuss the potential risks, the safest options available, and precautionary measures that should be taken when administering these therapies in these groups. While anti-VEGFs remain an essential tool in ophthalmology, careful patient selection, monitoring, and individualized treatment approaches are necessary to mitigate potential systemic risks. Further research is needed to refine our understanding of long-term safety.