June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Genetic markers within the Vascular Endothelial Growth Factor (VEGF) pathway as predictors of the response to the treatment of the Age Related Macular Degeneration (ARMD)
Author Affiliations & Notes
  • Irina Balikova
    Ophtalmology, UZ Ghent, Gent, Belgium
    Ophtalmology, Brugmann University Hospital, Brussels, Belgium
  • Laurence Postelmans
    Ophtalmology, Brugmann University Hospital, Brussels, Belgium
  • Brigitte Pasteels
    Ophtalmology, Brugmann University Hospital, Brussels, Belgium
  • Pascale Coquelet
    Ophtalmology, Brugmann University Hospital, Brussels, Belgium
  • Jeanette Catherine
    Ophtalmology, Brugmann University Hospital, Brussels, Belgium
  • Azra Efendic
    Ophtalmology, Brugmann University Hospital, Brussels, Belgium
  • Bernard Thienpont
    Flemish Biotechnology Institute VIB, Leuven, Belgium
  • Dieter Lambrechts
    Flemish Biotechnology Institute VIB, Leuven, Belgium
  • Footnotes
    Commercial Relationships   Irina Balikova, Novartis (F); Laurence Postelmans, None; Brigitte Pasteels, None; Pascale Coquelet, None; Jeanette Catherine, None; Azra Efendic, None; Bernard Thienpont, None; Dieter Lambrechts, None
  • Footnotes
    Support  NCT02762188
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 413. doi:
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    • Get Citation

      Irina Balikova, Laurence Postelmans, Brigitte Pasteels, Pascale Coquelet, Jeanette Catherine, Azra Efendic, Bernard Thienpont, Dieter Lambrechts; Genetic markers within the Vascular Endothelial Growth Factor (VEGF) pathway as predictors of the response to the treatment of the Age Related Macular Degeneration (ARMD). Invest. Ophthalmol. Vis. Sci. 2017;58(8):413.

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

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Abstract

Purpose : Age-related macular degeneration (ARMD) is a leading cause of visual impairment in the adult population in industrialized countries. The anti-Vascular Endothelial Growth Factor (VEGF) antibodies ranibizumab (Lucentis ) and bevacizumab (Avastin) together with the recently developed anti VEGF protein, Aflibercept (Eylea) have become the standard treatment for the wet form of ARMD. While most patients respond favourably to treatment, some do not. The difference seen in the responses suggests patient-specific factors influencing drug efficacy. We hypothesize that single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to response.
The aim of our study is to evaluate the association between a panel of 138 selected polymorphic markers in the VEGF pathway and the response to therapy with anti VEGF antibody for ARMD.

Methods : This is retrospective study. We collected genetic material and clinical information for 281 patients treated with anti VEGF antibodies with 3 loading injections and PRN treatment regiment for wet ARMD. For each patient, DNA from blood and demographic information were collected along with their visual acuity (VA) at baseline, after 3 loading injections and at 12 months; the number of injections received at 12 months and the changes in the retinal morphology. The latter included the central foveal thickness (CFT) at baseline, after 3 loading injections and at 12 months, as well as the presence or absence of intraretinal cysts, serous detachment of the neuroepithelium and pigment epithelial detachment at baseline and after 3 loading injections. Patients were classified as responders and non responders based on the VA, CFT and morphological signs of activity. DNA samples were genotyped using Sequenom for 158 tagging SNPs in the VEGF pathway. Association of SNPs to therapy response was assessed by binomial logistic regression.

Results : We found significant association between SNPs within the FLT4 (p=2.22E-06) and VEGFA (p=0.007283342) genes and the response to anti VEFG antibodies.

Conclusions : Defining the factors important for the treatment response has important consequences. It can help to develop individualized approach towards the treatment of ARMD and can point towards new therapeutic targets.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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