March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Gene Variants in the HTRA1 and ARMS2 genes and Outcome of Anti-VEGF Treatment in Neovascular AMD
Author Affiliations & Notes
  • Farshad Abedi
    Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
  • Sanj Wickremasinghe
    Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
  • Andrea J. Richardson
    Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
  • FM Amirul Islam
    Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
  • Robyn Guymer
    Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
  • Paul N. Baird
    Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships  Farshad Abedi, None; Sanj Wickremasinghe, None; Andrea J. Richardson, None; FM Amirul Islam, None; Robyn Guymer, None; Paul N. Baird, None
  • Footnotes
    Support  This project was partly funded by the National Health and Medical Research Council (NHMRC) project grants 590205 and 1008979, an NHMRC– Clinical Research Excellence grant 529923
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2931. doi:https://doi.org/
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      Farshad Abedi, Sanj Wickremasinghe, Andrea J. Richardson, FM Amirul Islam, Robyn Guymer, Paul N. Baird; Gene Variants in the HTRA1 and ARMS2 genes and Outcome of Anti-VEGF Treatment in Neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2931. doi: https://doi.org/.

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

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Abstract
 
Purpose:
 

To determine the contribution of genetic variants of known Age-related Macular Degeneration (AMD) risk associated genes with outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment in neovascular AMD

 
Methods:
 

Patients were recruited through public clinics at the Royal Victorian Eye and Ear Hospital, Melbourne. A total of 224 patients received intravitreal anti-VEGF (ranibizumab or bevacizumab) injections for untreated subfoveal choroidal neovascularisation (CNV) secondary to AMD and were followed over 12 months. Data relating to patient demographics, lesion characteristics, visual acuity (VA), using the Early Treatment Diabetic Retinopathy Study (ETDRS) charts, and number of injections, were collected. A total of 17 single nucleotide polymorphisms (SNPs) in known AMD genes (C3, LOC387715/ARMS2, CFH, HTRA1, CFHR, C2/BF and F13B) were genotyped and assessed for association using multivariate analysis adjusted for age, smoking status, baseline VA, number if injections, lesion type and size. Following Bonferroni correction, a significant p-value=0.003.

 
Results:
 

Mean age of patients was 78±6.7 years with a baseline VA of 51±17 ETDRS letter scores. Mean change in VA was +6.8±12.3, +5.1±13.4 and 3.3±14.9 letters at 3, 6 and 12 months, respectively. Patients received 4.2±1.1 and 6.4±2.3 injections in the first 6 and over 12 months, respectively. The AA genotype at rs11200638 (HTRA1 promoter SNP) predicted a better outcome of +7 and +9 letters after 6 (p= 0.003) and 12 months (p<0.0001), respectively. Similarly, the CC genotype at rs3793917 (LOC387715/ARMS2) was associated with increased VA outcome of +7 letters after 6 (p=0.006) and 12 months (p=0.001), whereas the TT genotype at rs10490924 (LOC387715/ARMS2) predicted a poorer VA response of -7 and -8 letters at 6 (p=0.004) and 12 months (p=0.001).

 
Conclusions:
 

Two SNPs, in the HTRA1 gene and LOC387715/ARMS2 gene, were associated with a significantly better VA outcome, whereas SNP rs10490924 in the LOC387715/ARMS2 gene was associated with a significantly poorer VA outcome for anti-VEGF treatment in neovascular AMD. These findings may indicate differing roles for variants in these 2 closely linked genes as well as providing potential avenues for pharmacogenetic interventions.

 
Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: outcomes/complications • genetics 
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