Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

Figures & data

Table 1 Comparison of current anti-VEGF agents for neovascular AMD

Anti-VEGF agents	Structure	Biological target	KD for VEGF165 (pM)	Molecular weight (kDa)	Approvals
Pegaptanib	Pegylated RNA aptamer	VEGF-A165 only^Citation15	50^Citation14	50^Citation16	FDA (2004) EMA (2005)
Bevacizumab	Recombinant humanized monoclonal lgG1 antibody	All isoforms of VEGF-A^Citation18	58^Citation19	l49^Citation19	FDA (2004) EMA (2005) CFDA (2010)
Ranibizumab	Recombinant humanized lgG1-κ isotype monoclonal antibody fragment	All isoforms of VEGF-A^Citation17	46^Citation19	48^Citation17	FDA (2006) EMA (2007) CFDA (2012)
Aflibercept	Fusion protein: domain 2 of VEGFR-1 and domain 3 of VEGFR-2 fused with lgG1 Fc	All isoforms of VEGF-A, VEGF-B, and PIGF^Citation23	0.5^Citation23	115^Citation19	FDA (2011) EMA (2012)
Conbercept	Fusion protein: domain 2 of VEGFR-1 and domains 3 and 4 of VEGFR-2 fused with lgG1 Fc	All isoforms of VEGF-A, VEGF-B, VEGF-C, and PIGF^Citation25	0.5^Citation24	143^Citation24	CFDA (2013)

Abbreviations: AMD, age-related macular degeneration; CFDA, China Food and Drug Administration; EMA, European medicines agency; FDA, US Food and Drug Administration; IgG, immunoglobulin G; K_D, binding affinity to VEGF-A₁₆₅; PIGF, placental growth factor; RNA, ribonucleic acid; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.

Figure 1 A framework to show the causes of resistance to anti-VEGF therapy and possible therapeutic approaches.

Abbreviations: AMD, age-related macular degeneration; VEGF, vascular endothelial growth factor.

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