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Association of ARMS2 genotype with response to anti-vascular endothelial growth factor treatment in polypoidal choroidal vasculopathy.

ABSTRACT: To investigate whether genetic risk variants for age-related macular degeneration (AMD) are associated with response to intravitreal anti-vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) patients.This prospective cohort study included 95 treatment-naïve patients that underwent anti-VEGF treatment for PCV for 12 months. Patients were genotyped for 10 single nucleotide polymorphisms in eight AMD-relevant genes. Genotypic association with visual and anatomic outcome measures at 12 months after initial treatment, including mean change in best-corrected visual acuity (BCVA) and total foveal thickness, visual gain of ? 15 letters, dry status on optical coherence tomography (OCT), pigment epithelial detachment (PED) regression on OCT, polyp regression on indocyanine green angiography, and injection numbers, were investigated using regression models with adjustment for non-genetic covariates under additive genetic model.In 81 patients who completed 12-month anti-VEGF monotherapy without photodynamic therapy, significant pharmacogenetic association was found between ARMS2 rs10490924 and PED regression on OCT. Proportions of PED regression were 26.4% for TT, 45.7% for TG, and 63.6% for GG genotype, showing additive effect of G allele for higher chance of PED regression (OR, 2.96; 95% CI, 1.38-6.36; corrected P = 0.043). For entire 95 patients, no significant association was found between candidate polymorphisms and receiving photodynamic therapy within 12 months.In PCV patients, ARMS2 rs10490924 showed association with anatomic therapeutic response to anti-VEGF, suggesting pharmacogenetic relationship.

SUBMITTER: Park UC

PROVIDER: S-EPMC5719580 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Association of ARMS2 genotype with response to anti-vascular endothelial growth factor treatment in polypoidal choroidal vasculopathy.

Park Un Chul UC Shin Joo Young JY Chung Hum H Yu Hyeong Gon HG

BMC ophthalmology 20171207 1

<h4>Background</h4>To investigate whether genetic risk variants for age-related macular degeneration (AMD) are associated with response to intravitreal anti-vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) patients.<h4>Methods</h4>This prospective cohort study included 95 treatment-naïve patients that underwent anti-VEGF treatment for PCV for 12 months. Patients were genotyped for 10 single nucleotide polymorphisms in eight AMD-relevant genes. Genotypic associ ...[more]

PMID: 29212537

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Project description:ImportanceCD11b+ immune cells have been implicated in the formation of choroidal neovascularization in experimental studies on animals and disease-association studies on humans. However, the clinical importance of such observations remains unknown.ObjectiveTo investigate whether the proportion of CD11b+ circulating monocytes is associated with the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV).Design, setting, and participantsThese observational cohort studies collected data from January 1, 2010, through December 31, 2013, and from January 1, 2015, through December 31, 2018. Fresh venous blood samples were acquired for flow cytometric immune studies in patients with neovascular AMD or PCV receiving treatment with aflibercept or ranibizumab as needed for 36 months. Patients (n = 81) without immune diseases were consecutively recruited from a single center in Denmark.ExposuresProportion of CD11b+ circulating monocytes.Main outcomes and measuresThe estimation of the number of intravitreal anti-VEGF injections given at 12, 24, and 36 months by the proportion of CD11b+ circulating monocytes and the correlation between these values. The angiogenic role of CD11b+ circulating monocytes was further evaluated by investigating the expression of the known proangiogenic receptor CCR2.ResultsEighty-one patients were included in the analysis (54% women; mean [SD] age, 76 [7] years). The proportion of CD11b+ monocytes at baseline positively estimated the future number of anti-VEGF injections at 12 (ρ = 0.77; 95% CI, 0.35-0.93; P = .004), 24 (ρ = 0.82; 95% CI, 0.44-0.95; P = .002), and 36 (ρ = 0.78; 95% CI, 0.34-0.94; P = .005) months. This association was also found retrospectively in a larger sample of patients with neovascular AMD at 12 (ρ = 0.46; 95% CI, 0.16-0.68; P = .004), 24 (ρ = 0.49; 95% CI, 0.20-0.70; P = .002), and 36 (ρ = 0.65; 95% CI, 0.41-0.80; P < .001) months and patients with PCV at 12 (ρ = 0.27; 95% CI, -0.28 to 0.68; P = .30), 24 (ρ = 0.60; 95% CI, 0.12-0.85; P = .02), and 36 (ρ = 0.70; 95% CI, 0.27-0.90; P = .005) months, suggesting that this association is not specific to AMD but rather reflects VEGF activity in neovascularization. CD11b+ monocytes highly coexpressed CCR2, an important monocytic marker of proangiogenic activity.Conclusions and relevanceResults of this study demonstrated that the proportion of circulating CD11b+ monocytes estimated and correlated with the number of anti-VEGF injections in patients with neovascular AMD and PCV. Additional longitudinal studies are needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy.

Dataset Information

Association of ARMS2 genotype with response to anti-vascular endothelial growth factor treatment in polypoidal choroidal vasculopathy.

Publications

Association of ARMS2 genotype with response to anti-vascular endothelial growth factor treatment in polypoidal choroidal vasculopathy.

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