Polymorphisms in Vascular Endothelial Growth Factor Receptor 2 Are Associated with Better Response Rates to Ranibizumab Treatment in Age-related Macular Degeneration

• Published in: Ophthalmology (Rochester, Minn.) Vol. 121; no. 4; pp. 905 - 910
• Main Authors: Hermann, Manuel M., MD, van Asten, Freekje, MD, Muether, Philipp S., MD, Smailhodzic, Dzenita, MD, Lichtner, Peter, PhD, Hoyng, Carel B., MD, PhD, Kirchhof, Bernd, MD, Grefkes, Christian, MD, den Hollander, Anneke I., PhD, Fauser, Sascha, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2014
• Subjects: Aged; Aged, 80 and over; Angiogenesis Inhibitors - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Coloring Agents; Female; Fluorescein Angiography; Genotype; Genotyping Techniques; Humans; Indocyanine Green; Male; Middle Aged; Ophthalmology; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Ranibizumab; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor Receptor-2 - genetics; Visual Acuity - physiology; Wet Macular Degeneration - drug therapy; Wet Macular Degeneration - genetics; Wet Macular Degeneration - physiopathology
• ISSN: 0161-6420; 1549-4713
• DOI: 10.1016/j.ophtha.2013.10.047

Purpose Intravitreal anti–vascular endothelial growth factor (VEGF) injections are currently the standard treatment for neovascular age-related macular degeneration (AMD), but a broad range of response rates has been observed. We evaluated the association of single nucleotide polymorphisms (SNPs) in VEGF genes and their receptors (VEGFR) with the response rate to ranibizumab in 366 patients with neovascular AMD. Design Case series study. Participants A total of 366 eyes of 366 patients with neovascular AMD. Methods Visual acuity (VA) was determined at baseline, after 3 monthly ranibizumab injections, and after 1 year of treatment. Genotyping of 126 SNPs in the genes encoding VEGF family members VEGFA, VEGFB, VEGFC, VEGFD ( FIGF ), and placental growth factor ( PGF ); VEGF receptors VEGFR1 ( FLT1 ), VEGFR2 ( KDR ), and VEGFR3 ( FLT4 ); and the gene encoding pigment epithelium-derived factor (PEDF) ( SERPINF1 ) was performed. Main Outcome Measures The changes in VA after 3 injections and after 1 year of treatment and their association with VEGF and VEGFR genotypes. Results Univariate analyses of variance (ANOVAs) revealed a significant effect of SNP rs4576072 in the VEGFR2 gene on VA change after 12 months (F[1,235]  = 14.05; P  = 0.02). A stepwise linear regression analysis returned a model ( P  = 0.01) with SNPs rs4576072 and rs6828477 in the VEGFR2 gene as independent predictors for VA change after 12 months, with a mean increase in VA of 0.26 on the logarithm of the minimum angle of resolution (logMAR) scale in patients with 3 contributing minor alleles compared with a loss of 0.03 logMAR in patients with no minor allele. Conclusions Polymorphisms in the VEGFR2/KDR gene significantly influence visual outcome in patients receiving ranibizumab treatment for neovascular AMD. This study shows that genetic variation partially explains the wide range of response to ranibizumab treatment, which in the future might help clinicians tailoring medical interventions to individual needs.