Why VEGF Makes Blood Vessels Leak—and How LYTENAVA Stops the Signal

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On July 24, 2026, the FDA approved LYTENAVA™ (bevacizumab-vikg) for the treatment of neovascular, or wet, age-related macular degeneration (nAMD). Developed by Outlook Therapeutics, LYTENAVA is notable as the first FDA-approved ophthalmic formulation of bevacizumab for intravitreal use in the United States. Bevacizumab has been widely used off-label in retinal disease for years through repackaged formulations of the oncology drug Avastin. LYTENAVA provides an ophthalmic-specific, preservative-free formulation manufactured specifically for injection into the eye. By binding VEGF-A and preventing activation of VEGF receptors, it suppresses both the abnormal vascular growth and increased vascular permeability that drive retinal fluid accumulation and vision loss in wet AMD. Why Does VEGF Make Blood Vessels Leak? Vascular endothelial growth factor, or VEGF, is best known as one of the body's principal signals for growing new blood vessels. Yet VEGF has another important property: it makes blood vessels more permeable. In fact, VEGF was originally identified for this activity and described as vascular permeability factor. The apparent contradiction makes sense when angiogenesis is viewed as a construction process. When tissue becomes hypoxic, stabilization of HIF-1α increases VEGF production. VEGF-A then binds VEGFR-2 on vascular endothelial cells, activating signaling that promotes endothelial survival, proliferation, and migration. But endothelial cells in a mature vessel are normally joined together by tightly regulated junctions. Before they can migrate outward and form a new vascular sprout, that stable architecture must be remodeled. VEGF helps initiate this process by altering endothelial junctions, particularly those involving VE-cadherin. Vascular permeability increases, allowing plasma proteins such as fibrinogen to enter the surrounding tissue. These proteins can contribute to a provisional extracellular matrix that supports endothelial migration and vascular remodeling. Under normal circumstances, this leaky state is temporary. As a new vessel matures, endothelial junctions stabilize, basement membrane develops, and supporting cells such as pericytes help establish a more durable vascular barrier. When a Normal Program Becomes Pathological In neovascular, or wet, age-related macular degeneration, this angiogenic program becomes chronically activated. Elevated VEGF promotes the formation of abnormal choroidal vessels that are poorly organized and excessively permeable. The consequence is not simply the presence of unwanted blood vessels. These vessels leak fluid and sometimes blood into and beneath the retina. The resulting edema disrupts retinal architecture and compromises photoreceptor function, threatening central vision. This explains an important aspect of anti-VEGF therapy. Drugs that neutralize VEGF do more than prevent additional vascular growth. By interrupting VEGF signaling, they also reduce the permeability of these abnormal vessels. Retinal fluid can therefore diminish relatively rapidly, even though the underlying neovascular complex has not simply disappeared. The biology reveals why the same molecule can drive both angiogenesis and vascular leakage. For VEGF, permeability is not necessarily a defect in the system—it is part of the angiogenic program. In wet AMD, the problem is that this normally temporary program fails to turn off.