Document Detail

Variants in the VEGFA gene and treatment outcome after anti-VEGF treatment for neovascular age-related macular degeneration.
MedLine Citation:
PMID:  23149126     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To determine the association of genetic variants of the VEGFA gene with outcome of anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (AMD).
DESIGN: A prospective cohort study.
PARTICIPANTS: We included 201 consecutive patients receiving anti-VEGF injections for neovascular AMD.
METHODS: Patients were followed over 12 months. They were treated with 3 initial monthly ranibizumab or bevacizumab injections. Thereafter, the decision to retreat was made by clinicians at each follow-up visit on the basis of retreatment criteria. Seven tagged single nucleotide polymorphisms (tSNPs) in the VEGFA gene were selected and examined. Multivariate data analysis was used to determine the role of each tSNP in treatment outcome.
MAIN OUTCOME MEASURES: The influence of selected VEGFA tSNPs on visual acuity (VA) outcome at 6 months.
RESULTS: Mean baseline VA was 51±17 Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. Overall, the mean change in VA from baseline was +6.5±12, +4.4±13.4, and +2.3±14.6 letters at 3, 6, and 12 months, respectively. The tSNP rs3025000 was the only SNP significantly associated (P<1 × 10(-4)) with visual outcome at 6 months with multiple correction. The presence of the T allele (TC or TT genotypes) at this tSNP predicted a better outcome of +7 letters at 6 months compared with the CC genotype. In a subgroup analysis, presence of the T allele predicted a significantly higher chance of the patients belonging to the responder group (gain of ≥5 letters from baseline) after 3, 6, and 12 months treatment (odds ratio, 2.7, 3.5, and 2.4; 95% confidence interval, 1.46-5.07, 1.82-6.71, and 1.27-4.57, respectively) than any other outcome group.
CONCLUSIONS: Pharmacogenetic association with anti-VEGF treatments may influence the visual outcomes in neovascular AMD. In patients with the T allele in tSNP rs3025000, there was a significantly better visual outcome at 6 months and a greater chance of the patients belonging to the responder group with anti-VEGF treatment at 3, 6, and 12 months. The VA outcomes of patients harboring the T allele at SNP rs3025000 were comparable with those of the pivotal clinical trials but with fewer injections, making the treatment perhaps more cost effective in certain subgroups of patients.
FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Farshad Abedi; Sanjeewa Wickremasinghe; Andrea J Richardson; Enes Makalic; Daniel F Schmidt; Sukhpal S Sandhu; Paul N Baird; Robyn H Guymer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-11
Journal Detail:
Title:  Ophthalmology     Volume:  120     ISSN:  1549-4713     ISO Abbreviation:  Ophthalmology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-03-07     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  7802443     Medline TA:  Ophthalmology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  115-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia.
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MeSH Terms
Aged, 80 and over
Angiogenesis Inhibitors / therapeutic use*
Antibodies, Monoclonal, Humanized / therapeutic use
Genotyping Techniques
Intravitreal Injections
Middle Aged
Polymorphism, Single Nucleotide*
Prospective Studies
Sequence Tagged Sites
Tomography, Optical Coherence
Treatment Outcome
Vascular Endothelial Growth Factor A / antagonists & inhibitors*,  genetics*
Visual Acuity / physiology*
Wet Macular Degeneration / drug therapy*,  genetics,  physiopathology
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal, Humanized; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 0/ranibizumab; 2S9ZZM9Q9V/bevacizumab

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