Department of Ophthalmology, University of Yamanashi, Chuo Yamanashi, Japan.
New York University School of Medicine, New York, NY, USA.
Sci Rep. 2020 Apr 28;10(1):7188. doi: 10.1038/s41598-020-64301-z.
In the present study, we investigated the association between susceptible genetic variants to age-related macular degeneration (AMD) and response to as-needed intravitreal aflibercept injection (IAI) therapy for exudative AMD including both typical neovascular AMD and polypoidal choroidal vasculopathy (PCV) over 12-months. A total of 234 patients with exudative AMD were initially treated with 3 monthly IAI and thereafter as-needed IAI over 12 months. Seven variants of 6 genes including ARMS2 A69S (rs10490924), CFH (I62V:rs800292 and rs1329428), C2-CFB-SKIV2L(rs429608), C3 (rs2241394), CETP (rs3764261) and ADAMTS-9 (rs6795735) were genotyped for all participants using TaqMan technology. After adjusting for age, gender, baseline BCVA and AMD subtype, A (protective) allele of C2-CFB-SKIV2L rs429608 was associated with visual improvement at 12-month (P = 0.003). Retreatment was associated with T(risk) allele of ARMS2 A69S (P = 2.0 × 10; hazard ratio: 2.18:95%CI: 1.47-3.24) and C(risk) allele of CFH rs1329428 (P = 2.0 × 10; hazard ratio: 1.74:95%CI: 1.16-2.59) after adjusting for the baseline confounders. The need for additional injections was also associated with T allele of ARMS2 A69S (P = 1.0 × 10) and C allele of CFH rs1329428 (P = 3.0 × 10) after adjusting for the baseline confounders. The variants of ARMS2 and CFH are informative for both physicians and patients to predict recurrence and to quantify the need for additional injections.
在本研究中，我们调查了与年龄相关性黄斑变性（AMD）易感性遗传变异体相关的风险，以及对渗出性 AMD 包括典型新生血管性 AMD 和息肉样脉络膜血管病变（PCV）的按需玻璃体腔内阿柏西普注射（IAI）治疗的反应，随访 12 个月。共有 234 例渗出性 AMD 患者最初接受 3 个月 IAI 治疗，之后在 12 个月内按需接受 IAI 治疗。使用 TaqMan 技术对所有参与者的 6 个基因的 7 个变体（ARMS2 A69S [rs10490924]、CFH [I62V：rs800292 和 rs1329428]、C2-CFB-SKIV2L [rs429608]、C3 [rs2241394]、CETP [rs3764261]和 ADAMTS-9 [rs6795735]）进行了基因分型。在调整年龄、性别、基线 BCVA 和 AMD 亚型后，C2-CFB-SKIV2L rs429608 的 A（保护性）等位基因与 12 个月时的视力改善相关（P=0.003）。在调整基线混杂因素后，重复治疗与 ARMS2 A69S 的 T（风险）等位基因（P=2.0×10；危险比：2.18：95%CI：1.47-3.24）和 CFH rs1329428 的 C（风险）等位基因（P=2.0×10；危险比：1.74：95%CI：1.16-2.59）相关。在调整基线混杂因素后，需要额外注射也与 ARMS2 A69S 的 T 等位基因（P=1.0×10）和 CFH rs1329428 的 C 等位基因（P=3.0×10）相关。ARMS2 和 CFH 的变体对医生和患者都有信息，可以预测复发，并量化额外注射的需求。
