Universität zu Köln

Hermann, Manuel M., van Asten, Freekje ORCID: 0000-0002-8141-4234, Muether, Philipp S., Smailhodzic, Dzenita, Lichtner, Peter, Hoyng, Carel B., Kirchhof, Bernd, Grefkes, Christian ORCID: 0000-0002-1656-720X, den Hollander, Anneke I. and Fauser, Sascha (2014). Polymorphisms in Vascular Endothelial Growth Factor Receptor 2 Are Associated with Better Response Rates to Ranibizumab Treatment in Age-related Macular Degeneration. Ophthalmology, 121 (4). S. 905 - 911. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1549-4713

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Abstract

Purpose: Intravitreal antievascular 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. Ophthalmology 2014;121:905-910 (C) 2014 by the American Academy of Ophthalmology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hermann, Manuel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Asten, Freekje UNSPECIFIED orcid.org/0000-0002-8141-4234 UNSPECIFIED Muether, Philipp S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Smailhodzic, Dzenita UNSPECIFIED UNSPECIFIED UNSPECIFIED Lichtner, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyng, Carel B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirchhof, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Grefkes, Christian UNSPECIFIED orcid.org/0000-0002-1656-720X UNSPECIFIED den Hollander, Anneke I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-441623
DOI:	10.1016/j.ophtha.2013.10.047
Journal or Publication Title:	Ophthalmology
Volume:	121
Number:	4
Page Range:	S. 905 - 911
Date:	2014
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1549-4713
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COMPLEMENT FACTOR-H; INTRAVITREAL RANIBIZUMAB; VEGF; BEVACIZUMAB; VARIANTS; THERAPY; Y402H; GENE; CFH Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44162