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Anjali Shah, Steven Williams, Caroline Baumal, Bernard Rosner, Jay S Duker, Johanna Seddon; Predictors of Response to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment of Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3788.
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To identify genetic and environmental factors that influence response to treatment with intravitreal anti-vascular endothelial growth factor (VEGF) medication for neovascular age-related macular degeneration (nAMD), and to review existing literature on this topic.
A retrospective chart review of 72 patients previously enrolled in genetic and epidemiologic studies of AMD and treated at a single institution with either bevacizumab or ranibizumab for nAMD was conducted. Best corrected Snellen visual acuity (VA) and central foveal thickness (CFT) on OCT were recorded for each treatment visit and each post-treatment follow up visit, including 6 and 12 month visits. Demographic, lifestyle, and genotype information including all known AMD genes to date were examined, and a CFH risk score including 3 loci was calculated. Primary outcome measures were change in VA and OCT-CFT from baseline to 12 months.
Greater improvement in VA was associated with low-risk CFH genotypes. The CFH Y402H and CFH rs1061147 non-risk genotypes were both associated with improved VA (p-values assessing differences in slope estimates according to genotype =0.026 and 0.028, respectively). A low CFH risk score was associated with improvement in VA after anti-VEGF treatment (p=0.019), while a high risk score was not (p=0.77). The difference in outcome between the low and high risk CFH groups was statistically significant (p=0.037). Improvement in VA for non-risk genotypes was suggested for the following genes: ABCA1, CETP, COL8A1, COL10A1, ARMS2/HTRA1, DDR1, and ADAMTS9/ADMTS9-AS2, although there were no significant differences in outcome between non-risk and risk genotypes. Younger age groups and males trended toward improved VA, but the p-values were not statistically significant. Regarding the outcome OCT-CFT, all categories for each demographic, behavioral, and genetic covariate were significantly associated with improvement in OCT-CFT over time, and a low CFH risk score was significantly associated with a greater reduction in central foveal thickness (p for comparing low and high CFH risk groups=0.041).
Patients with fewer high-risk alleles in the CFH gene had better VA and OCT-CFT outcomes after anti-VEGF treatment for nAMD.
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