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Jaclyn Kovach, Anita Agarwal, Stephen Schwartz, Milam Brantley, William Cade, Jonathan Haines, Margaret Pericak-Vance; The Role of Genetics in Response to Anti-VEGF Therapy for Wet AMD. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6186.
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To evaluate the relationship between high-risk genetic polymorphisms and the response to anti-VEGF therapy in wet AMD.
Forty-three Caucasian patients with wet AMD (AREDS grade 5) who were treated with bevacizumab, ranibizumab, and/or aflibercept were followed for 1 year with complete eye exams and OCT imaging Q1-3 months. Fundus photography and fluorescein angiography were performed periodically. Individuals who gained at least 2 lines of Snellen vision with a reduction or absence of intraretinal/subretinal fluid at the end of 1 year were labeled “good responders.” Those that lost at least 2 lines of Snellen vision with persistent/increased intraretinal/subretinal fluid were classified as “poor responders.” The remaining patients were categorized as “maintainers.” Genomic DNA was extracted from whole blood and analyzed. Patients were genotyped and two types of risk scores (RS) were created that computed the number of high risk alleles for each individual. The 16RS considered 16 single nucleotide polymorphisms (SNP) identified as loci reaching genome-wide significance, and the 4RS considered CFH rs10737680, C2/CFB rs429608, ARMS2 rs10490924, and C3 rs2230199.
Of 43 patients, 16 were good responders, 19 were maintainers, and 8 were poor responders. A strong correlation existed between the two types of risk scores. Maintainers had a higher 16RS and 4RS than the other two groups. Average 16RS (p = 0.0197) and 4RS (p= 0.0186) were significantly lower in good responders compared to maintainers, and individual risk allele frequencies for the 4 major SNPs were lower in good responders compared to maintainers. Both risk scores were slightly lower in poor responders compared to maintainers, but the differences were not statistically significant.
Individuals that maintained stable vision with anti-VEGF therapy had greater genetic risks than those with good responses. Further investigation of the role of genetics and environmental factors in response to therapy in a larger sample size of wet AMD patients may bring us closer to personalized treatment for AMD.
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