April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
The Role of Genetics and Smoking in Response to Anti-VEGF Therapy for Wet AMD
Author Affiliations & Notes
  • Jaclyn L. Kovach
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples, Florida
  • Anita Agarwal
    Ophthalmology,
    Vanderbilt University, Nashville, Tennessee
  • William Cade
    Genetics, University of Miami Miller School of Medicine, Miami, Florida
  • William K. Scott
    Genetics, University of Miami Miller School of Medicine, Miami, Florida
  • Kelly Taylor
    Genetics,
    Vanderbilt University, Nashville, Tennessee
  • Stephen G. Schwartz
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples, Florida
  • Paul Gallins
    Genetics, University of Miami Miller School of Medicine, Miami, Florida
  • Gaofeng Wang
    Genetics, University of Miami Miller School of Medicine, Miami, Florida
  • Jonathan L. Haines
    Genetics,
    Vanderbilt University, Nashville, Tennessee
  • Margaret A. Pericak-Vance
    Genetics, University of Miami Miller School of Medicine, Miami, Florida
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5231. doi:
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    • Get Citation

      Jaclyn L. Kovach, Anita Agarwal, William Cade, William K. Scott, Kelly Taylor, Stephen G. Schwartz, Paul Gallins, Gaofeng Wang, Jonathan L. Haines, Margaret A. Pericak-Vance; The Role of Genetics and Smoking in Response to Anti-VEGF Therapy for Wet AMD. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5231.

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

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Abstract
 
Purpose:
 

To evaluate the relationship between high-risk genetic polymorphisms and smoking history and the response to anti-VEGF therapy in wet AMD.

 
Methods:
 

Case series of 52 patients with wet AMD treated with an anti-VEGF agent, bevacizumab and/or ranibizumab, for at least 1 year. Genotypes at ARMS2 A69S and CFH Y402H were identified from DNA analysis with genomic screen and participants completed a smoking history questionnaire. Patients had been treated with an intravitreal injection of an anti-VEGF agent according to PrONTO study protocol for at least one year. Eyes with vision loss secondary to cataract, geographic atrophy, laser scar or RPE rip were excluded. Response to treatment was dichotomized into those that gained at least 2 lines of Snellen vision and had a reduction in intraretinal or subretinal fluid (responders) and those that maintained or lost vision and had persistent, recurrent or increased intraretinal or subretinal fluid (non-responders).

 
Results:
 

Of the 52 total patients with wet AMD (diagnosed grade 5 AMD in at least 1 eye), 37 (71%) are non-responders compared to 15 (29%) responders. We found that responders were more likely to have at least one risk allele for both genes (CFH and ARMS2) and non-responders were more likely to have no risk alleles (p=0.02683). A higher proportion of responders than non-responders carry at least one risk allele at ARMS2 (85% vs. 55%), at CFH (100% vs. 81%) or at both genes (87% vs. 51%). No significant association was detected between response to treatment and the individual risk factors (Fisher’s exact test p-values: CFH- 0.0933, ARMS2- 0.0891,Smoking (past)- 0.7455, Smoking (present)-1).

 
Conclusions:
 

We found a statistically significant association between CFH and ARMS2 risk alleles and a positive response to anti-VEGF treatment. Expanding our sample size and testing other high risk alleles will further elucidate the relationship between genetic AMD risk factors and treatment response.

 
Keywords: age-related macular degeneration • genetics • vascular endothelial growth factor 
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