Intravitreal Anti-VEGF

• CNVM and DMO are driven by upregulation of pro-angiogenic growth factor: vascular endothelial growth factor (VEGF)

• From platelet-derived growth factor family
• Breaks down the inner blood-retinal barrier
• Increases capillary permeability
• Upregulated in hypoxia via hypoxia inducible factor (HIF)

• Anti-VEGF therapies bind to soluble VEGF and block its activity by preventing its binding to VEGF receptors eg. VEGF-R1 and VEGF-R2

• These are tyrosine kinase linked receptors

• Ranibizumab (Lucentis): monoclonal recombinant human Fab against VEGF

• Binds VEGF: all active forms of VEGF-A and their active degradation products

• Lacks an Fc region so is very small and can easily penetrate the retina

• Bevacizumab (Avastin): also a recombinant humanized antibody but is full-length (ie. is a larger molecule) so may persist in the body longer

• Has two antigen binding domains rather than one
• Aflibercept: a recombinant fusion protein acting as a VEGF receptor decoy

• ‘Traps’ all available VEGF with greater affinity and prevents it binding to VEGF receptors

See Part 2 package for further exploration of macular diseases and their management.