Abstract
We investigated whether polygenic risk score (PRS) was associated with one-year outcome of as-needed aflibercept therapy for exudative age-related macular degeneration (AMD), including AMD (n = 129) and polypoidal choroidal vasculopathy (n = 132). A total of 261 patients were treated with as-needed intravitreal aflibercept injection (IAI) after three monthly IAIs and the completion of a one-year follow-up. One hundred and seventy-two healthy volunteers served as controls. Genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), SKIV2L-C2-CFB (rs429608), C3 (rs2241394), ADAMTS-9 (rs6795735) and CETP (rs3764261) was performed for all participants. A total of 63 PRSs were quantified. There was a positive association between the PRS involving ARMS2, CFH, C3, and ADAMTS-9 and best-corrected visual acuity at twelve months (p = 0.046, multiple regression analysis). When comparing PRSs of patients requiring retreatment and of patients without retreatment, 35 PRSs were significantly greater in patients requiring retreatment than in patients without requiring retreatment, with the PRS involving ARMS2 and CFH being most significantly associated (p = 1.6 × 10−4). The number of additional injections was significantly associated with 40 PRSs and the PRS involving ARMS2 and CFH showed a most significant p-value (p = 2.42 × 10−6). Constructing a PRS using a combination with high-risk variants might be informative for predicting the response to IAI for exudative AMD.
Highlights
Age-related macular degeneration (AMD), the leading cause of moderate and severe irreversible vision loss in people over 50 years of age worldwide, is a chronic inflammatory disease with a multifactorial etiology including the combined effects of multiple genes and environmental factors [1,2]
Given the reported association between genetic variants and various clinical phenotypes in exudative AMD [16,17,18,19,20], it is reasonable to hypothesize that genetic factors may be associated with response to intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors, including aflibercept
The present study quantified 63 polygenic risk score (PRS) to determine the potential association with one-year outcomes following as-needed aflibercept therapy exudative AMD
Summary
Age-related macular degeneration (AMD), the leading cause of moderate and severe irreversible vision loss in people over 50 years of age worldwide, is a chronic inflammatory disease with a multifactorial etiology including the combined effects of multiple genes and environmental factors [1,2]. The association of almost 20 genes with neovascular AMD has been demonstrated in Asian populations [3]. The advent of vascular endothelial growth factor (VEGF) inhibitors (bevacizumab, ranibizumab, aflibercept) revolutionized the treatment of exudative AMD. Intravitreal administration of VEGF inhibitors is currently the first-line treatment option for exudative AMD. Aflibercept is a recombinant fusion glycoprotein binding to all isoforms of VEGF-A, VEGF-B, and placental growth factor with approximately 100 times higher binding affinity compared with bevacizumab and ranibizumab [4]. The VIEW1/2 study demonstrated that bimonthly intravitreal aflibercept injection (IAI) following an initial three-month IAI course is non-inferior to the monthly administration of ranibizumab regarding the improvement of best-corrected visual acuity as an endpoint [5]. Pro re nata (PRN) is an alternative regimen to monthly dosing for treating exudative AMD [6]
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