A patient with wet AMD on monthly intravitreal ranibizumab develops persistent subretinal fluid despite 6 monthly injections. Switching to intravitreal aflibercept is considered. The pharmacological reason aflibercept may overcome anti-VEGF resistance in this scenario is:
- A Aflibercept is a monoclonal antibody with higher affinity for VEGF-A165 than ranibizumab
- B Aflibercept has a longer half-life due to its IgG Fc region and additionally binds placental growth factor (PlGF) and VEGF-B ✓
- C Aflibercept inhibits VEGF by blocking the VEGFR-2 tyrosine kinase intracellularly
- D Aflibercept has anti-inflammatory properties independent of VEGF blockade
Correct answer: B. Aflibercept has a longer half-life due to its IgG Fc region and additionally binds placental growth factor (PlGF) and VEGF-B
Explanation
Aflibercept (VEGF Trap) is a fusion protein with the binding domains of VEGFR-1 and VEGFR-2 fused to an IgG Fc region. Its broader binding profile (VEGF-A, VEGF-B, and PlGF) and very high binding affinity (Kd ~0.5 pM, approximately 100-fold higher than ranibizumab for VEGF-A) may overcome tachyphylaxis. Ranibizumab is a Fab fragment; aflibercept is not a monoclonal antibody and does not act intracellularly via kinase inhibition.
Reference: Khurana Comprehensive Ophthalmology, 7th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.