April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Polymorphic Variations Affecting Response To Anti-VEGF Therapy In Patients With Exudative Age-related Macular Degeneration
Author Affiliations & Notes
  • Vinson M. Wang
    Laboratory of Immunology,
    National Eye Institute, Bethesda, Maryland
  • Richard B. Rosen
    Ophthalmology, New York Eye & Ear Infirmary, New York, New York
  • Catherine B. Meyerle
    Division of Epidemiology and Clinical Applications,
    National Eye Institute, Bethesda, Maryland
  • Shree K. Kurup
    Department of Ophthalmology, Wake Forest University, Winston Salem, North Carolina
  • Katy Tai
    Ophthalmology, New York Eye & Ear Infirmary, New York, New York
  • Matthew Pomykala
    Ophthalmology, New York Eye & Ear Infirmary, New York, New York
  • Emily Y. Chew
    Division of Epidemiology and Clinical Applications,
    National Eye Institute, Bethesda, Maryland
  • Chi-Chao Chan
    Laboratory of Immunology,
    National Eye Institute, Bethesda, Maryland
  • Jingsheng Tuo
    Laboratory of Immunology,
    National Eye Institute, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  Vinson M. Wang, None; Richard B. Rosen, None; Catherine B. Meyerle, None; Shree K. Kurup, None; Katy Tai, None; Matthew Pomykala, None; Emily Y. Chew, None; Chi-Chao Chan, None; Jingsheng Tuo, None
  • Footnotes
    Support  NEI Intramural Research Program
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1231. doi:
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      Vinson M. Wang, Richard B. Rosen, Catherine B. Meyerle, Shree K. Kurup, Katy Tai, Matthew Pomykala, Emily Y. Chew, Chi-Chao Chan, Jingsheng Tuo; Polymorphic Variations Affecting Response To Anti-VEGF Therapy In Patients With Exudative Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1231.

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

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Abstract

Purpose: : Age-related macular degeneration (AMD) is the leading cause of central, irreversible visual impairment in the elderly and genetic components are major contributors to disease pathogenesis. Currently, the most widely utilized therapy for neovascular AMD is intravitreal administration of anti-vascular endothelial growth factor (VEGF) antibodies such as bevacizumab and ranibizumab. However, some patients with AMD do not respond adequately to this therapy. The purpose of this study is to determine if a pharmacogenomic mechanism plays a role in the differentiated therapy response.

Methods: : Ninety-three AMD patients who received anti-VEGF treatments were included in this study. The patients were classified into two groups: the responders (65 patients) and the non-responders (28 patients). The non-responders were defined as those who maintained or developed new areas with macular fluid, developed macular scarring, or lost more than 15 letters of vision after 6 months of anti-VEGF therapy. The responders were defined as those who maintained or improved vision and showed a decrease in subretinal fluid after 6 months follow-up. Peripheral blood leukocytes were obtained for DNA extraction and plasma collection. Genotypic variations of 22 single nucleotide polymorphisms (SNPs) within CFH, HTRA1, IL-17, IL-23R, CYP3A, LEP and VEGFA were analyzed by Taqman SNP assay.

Results: : Of the 22 SNPs that were analyzed, only one SNP, IL-23R rs10127763 was associated with response to anti-VEGF therapy. We observed a higher frequency of allele A in the non-responders (10/56) compared to the responders (10/130) for the IL-23R SNP. The frequency of allele A in responders was 7.7% compared to 17.9% in non-responders (p=0.04) with an odds ratio of 2.61 and 95% CI. We also found differing allelic frequencies in two other IL-23R SNPs, rs1321157 (48.5% in responders vs. 60.7% in non-responders) and rs7530511 (10.4% in responders vs. 17.9% in non-responders), however, these results were not statistically significant (p=0.12 and p=0.16 respectively).

Conclusions: : These results suggest that gene variation within IL-23R might contribute to the distinct efficacy of anti-VEGF therapy for neovascular AMD. Larger sample size and cytokine analyses are needed to confirm the association and functional relevance of the SNP.

Keywords: drug toxicity/drug effects • neovascularization • gene/expression 
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