A 72-year-old woman with neovascular AMD receives her 8th intravitreal bevacizumab injection. OCT shows persistent sub-retinal fluid despite monthly injections. The ophthalmologist switches to intravitreal aflibercept. Compared to bevacizumab and ranibizumab, aflibercept has a higher binding affinity for VEGF primarily because it:
- A Is a humanized monoclonal antibody with a longer half-life
- B Inhibits VEGF receptor tyrosine kinase intracellularly
- C Is a fusion protein binding both VEGF-A and placental growth factor (PlGF) with picomolar affinity ✓
- D Contains an aptamer sequence that targets VEGF-165 specifically
Explanation
Aflibercept is a recombinant fusion protein combining VEGF-binding domains from VEGFR-1 and VEGFR-2 fused to the Fc fragment of IgG1. This design gives it sub-picomolar binding affinity for VEGF-A (approximately 100-fold higher than ranibizumab) and it additionally binds VEGF-B and placental growth factor (PlGF). This broad and high-affinity binding explains its efficacy in cases resistant to bevacizumab/ranibizumab. Bevacizumab and ranibizumab are monoclonal antibodies targeting VEGF-A only. Pegaptanib is the aptamer that targets VEGF-165 specifically. No intravitreal anti-VEGF acts intracellularly.
Reference: Khurana Comprehensive Ophthalmology, 7th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.