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

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. Anti-vascular endothelial growth factor (anti-VEGF) injections are widely used to treat eye diseases such as diabetic macular edema and age-related macular degeneration by blocking abnormal blood vessel growth in the retina. Although these drugs are injected into the eye, small amounts can enter the bloodstream, raising concerns about their effects on other organs, especially the kidneys, heart, and brain. This review explores whether anti-VEGF therapy affects kidney function, increases the risk of heart disease, or impacts the nervous system. Most studies suggest that these drugs are generally safe for the kidneys, but some research indicates a possible risk of kidney damage in patients with preexisting conditions. Similarly, while there is no strong evidence that anti-VEGFs cause heart problems, certain patients—such as those with a history of heart disease—may be at higher risk of complications such as stroke or heart attacks. There are also concerns about potential effects on brain health, with some studies linking anti-VEGFs to an increased risk of stroke and cognitive decline. Special precautions are needed for pregnant and breastfeeding women, as well as premature infants receiving these treatments for retinopathy of prematurity. Overall, anti-VEGF therapy remains a crucial treatment for vision-threatening diseases, but doctors should monitor patients carefully, especially those with underlying health conditions.