June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Single nucleotide polymorphisms in the VEGFR2 gene influences treatment responsiveness in neovascular macular degeneration
Author Affiliations & Notes
  • Usha Chakravarthy
    Ctr for Vascular & Vision Sciences, Queens University of Belfast, Belfast, United Kingdom
  • Giuliana Silvestri
    Ctr for Vascular & Vision Sciences, Queens University of Belfast, Belfast, United Kingdom
  • Ruth E Hogg
    Ctr for Vascular & Vision Sciences, Queens University of Belfast, Belfast, United Kingdom
  • Levente A Toth
    Ctr for Vascular & Vision Sciences, Queens University of Belfast, Belfast, United Kingdom
  • Philip Earle
    Ctr for Vascular & Vision Sciences, Queens University of Belfast, Belfast, United Kingdom
  • Gareth J McKay
    Centre for Public Health, Queens University, Belfast, United Kingdom
  • Footnotes
    Commercial Relationships Usha Chakravarthy, Allergan (F), Novartis (F), Ophthotech (C), Roche (F); Giuliana Silvestri, None; Ruth Hogg, None; Levente A Toth, None; Philip Earle, None; Gareth McKay, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1656. doi:
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      Usha Chakravarthy, Giuliana Silvestri, Ruth E Hogg, Levente A Toth, Philip Earle, Gareth J McKay; Single nucleotide polymorphisms in the VEGFR2 gene influences treatment responsiveness in neovascular macular degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1656.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To examine the role of genetic variability in determining treatment responsiveness to anti vascular endothelial growth factor (VEGF) therapy in neovascular age macular degeneration (AMD).

Methods: We selected 68 single nucleotide polymorphisms (SNP’s) from genes previously identified as susceptibility factors in AMD and those in relevant biological pathways, along with 43 SNP’s from genes encoding the VEGF protein and or its cognate receptors (VEGFR1 and R2) as this pathway is targeted by treatment. Following ethics approval, we enrolled consecutive patients (Feb 2009 to October 2011) attending a retina clinic with a diagnosis of neovascular AMD undergoing treatment with an anti VEGF. We assigned responder status based on optical coherence tomography. We defined two morphological outcomes. Macula fluid free at any time after treatment initiation or macula fluid free within the loading phase of 3 treatments. Statistical analysis was performed on pLINK to identify SNP’s with a p value < 0.01 or less. Multivariate regression models were run with each of the two outcomes as the dependent variable and with age, gender, smoking status and the identified SNP’s as explanatory variables .

Results: Of the 467 participants enrolled29 excluded from the analysis (age < 50, not exudative AMD or genetic analysis not performed). 65% (275) were classified as macula fluid free any time and forty percent (172) as macula fluid free within 3 months. In the unadjusted analysis we observed statistically significant associations between several SNP’s in the VEGFR2 gene. We selected the SNP 17085262 with the lowest p value as the explanatory variable of interest.. The model confirmed significant association with responder status in a dose dependent manner, OR= 1.38 (CI; 0.99, 2.18) for a single copy of the minor allele and OR = 3.22, (CI, 1.07, 9.73) for homozygotes. No significant associations were identified with respect to a fluid free macula within 3 treatments.

Conclusions: In addition to clinical factors such as timely treatment administration, lesion size and composition and initial acuity, morphological responsiveness to anti VEGF therapy appears to be influenced by genetic variability in the VEGFR2 gene. Our findings are in accord with biological plausibility of effect as VEGFR2 encodes the cognate protein receptor that mediates the pathophysiological effects of VEGF.

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