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Genetic association with response to intravitreal ranibizumab in patients with neovascular AMD

Kloeckener-Gruissem B., and Barthelmes, D. and Labs, S. and Schindler, C. and Kurz-Levin M., and Michels, S. and Fleischhauer, J. and Berger, W. and Sutter, F. and Menghini, M.. (2011) Genetic association with response to intravitreal ranibizumab in patients with neovascular AMD. Investigative ophthalmology & visual science, Vol. 52, H. 7. pp. 4694-4702.

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Official URL: http://edoc.unibas.ch/dok/A6002212

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Abstract

Purpose. Neovascular age-related macular degeneration (AMD) resulting in decreased central vision severely impairs affected individuals. Current standard treatment is an intravitreal anti-VEGF therapy (ranibizumab), but responses to treatment show large variability. Genetic factors that influence AMD and that affect the outcome of ranibizumab treatment were sought within a sample of Swiss patients. Methods. Changes in visual acuity (VA) after initiation of anti-VEGF treatment were observed during 12 months, and percentiles of VA were calculated. Genotypes of polymorphisms in known AMD susceptibility loci (CFH, CFB, HTRA1, AMRS2, and VEGFA) as well as not yet reported AMD-associated genes (KDR, LRP5, and FZD4) were determined, and their frequencies were compared. Results. Of the 309 eyes included in the study, 243 completed VA assessment. On average, 3.9 +/-2.6 ranibizumab injections were administered. Based on the change in visual acuity, two responder groups were established: 63 eyes were assigned to the poor responders (/=75th percentile). Individuals with genotype CC of p.Y402H in CFH had a decreased chance of positive treatment outcome compared with those with the CT and TT genotypes (P = 0.005 and P = 0.006). In this study, the genotype combination of AG at CFH with CT at FZD4 (SNP rs10898563) promised an increased chance of positive treatment outcome (P = 0.004). Furthermore, the association with the known genetic susceptibility loci CFH, HTRA1, and AMRS2 were confirmed, and a risk-conferring polymorphism in one new locus, LRP5, was identified. Conclusions. Genetic predisposition may account for the variability in response to anti-VEGF treatment
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Infectious Disease Modelling > Epidemiology and Transmission Dynamics (Smith)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin
UniBasel Contributors:Schindler, Christian
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
ISSN:0146-0404
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:17

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