The "V" in VEGF
This fundamental biological process acts as nature’s "construction crew," building new blood vessels for wound healing, but can be hijacked by tumors to fuel growth
Angiogenesis
This specific receptor isoform is the primary driver of angiogenesis in both tumors and the retina
VEGFR-2
Approved in 2003, it was the first full-length humanized monoclonal antibody and is the cheapest option at approximately $62 per dose
Bevacizumab (Avastin)
This remains the primary route of delivery for modern anti-neovascular retinal therapies
intravitreal injection
This initial step of the cascade occurs when tissues sense a lack of oxygen or nutrients and release "flares" such as VEGF to recruit endothelial cells.
angiogenic factor production
Discovered in 1989, this endogenous molecule is the "star of the show" and a central player in the angiogenesis cascade
Vascular Endothelial Growth Factor (VEGF)
Receptor activation produces these two substances, which contribute to vessel dilation and leaky, swollen tissue
Nitric Oxide (NO) and Prostaglandin I2 (PGI2)
This drug is a cleaved Fab fragment of bevacizumab, engineered for enhanced affinity and safety in the eye
Ranibizumab (Lucentis)
This serious ocular infection is a potential adverse reaction that surgeons try to avoid by ensuring there is no active surface infection before treatment
endophthalmitis
During the endothelial cell activation stage, cells begin "clearing the construction site" by breaking down this specific structural barrier.
basement membrane
Of the five VEGF isoforms, this is the one clinicians care about most for treating wet AMD and diabetic eye disease
VEGF-A
This protein acts as a "partner in crime" with VEGF, destabilizing the endothelial barrier and promoting vascular leakage
Angiopoietin-2 (Ang2)
This "pan-VEGF trap" is a soluble decoy receptor that fused human IgG with receptor fragments to increase binding efficiency
Aflibercept (Eylea)
Anti-neovascular drugs first gained notoriety in this medical field due to their role in inhibiting tumor metastasis
oncology
In step six, endothelial cells do not just sit still; they perform this action, moving toward the angiogenic signal like "ants marching toward a dropped cookie crumb."
directional migration
These two specific isoforms are the "specialists" responsible for lymphangiogenesis
VEGF-C and VEGF-D
These agents act like "molecular sponges," binding directly to VEGF to prevent it from interacting with receptors
Ligand binding agents
This novel agent is the first to uniquely target both Ang2 and VEGF-A simultaneously
Faricimab (Vabysmo)
This drug offers the longest dosing flexibility, with some patients extending treatments up to every 16 weeks
faricimab
To ensure blood flow and avoid "dead-end streets," the cascade must progress from forming hollow tubes to this vital ninth step
loop formation
These two members of the glycoprotein family are primarily associated with embryonic vessel development
VEGF-B and Placental Growth Factor (PLGF)
This class of drugs, including sunitinib, blocks signaling at the receptor level but is not yet FDA-approved for ocular use
Tyrosine Kinase Inhibitors (TKIs)
Before the anti-VEGF revolution, this laser-based therapy was the mainstay for wet AMD, though it was often compared to using a squirt gun on a house fire
photocoagulation (or PRP)
These are two common contraindications for administering any intravitreal anti-VEGF biologic
ocular infection and active ocular inflammation
Pathological angiogenesis often fails at this final step, where pericytes and smooth muscle cells are supposed to move in to keep vessels from being fragile and leaky.
vascular stabilization