Potential antiedematous effects of intravitreous anti-VEGF, unrelated to VEGF neutralization

The intravitreous injection of therapeutic proteins that neutralize vascular endothelial growth factor (VEGF) family members is efficient to reduce macular edema associated with wet age-related macular degeneration (AMD), retinal vein occlusion (RVO) and diabetic retinopathy (DR). It has revolutionized the visual prognosis of patients with macular edema. The antiedematous effect is dependent on an intravitreous dose of drug, which varies between patients and requires frequent and repeated injections to maintain its effects. At the time when optimizing the duration of anti-VEGF effects is a major challenge, understanding how anti-VEGF reduces macular edema is crucial. We discuss herein how antiVEGF exerts antiedematous effects and raise the hypothesis that mechanisms, unrelated to VEGF neutralization, might have been underestimated.