Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study

IF 4.9 2区医学 Q1 OPHTHALMOLOGY Clinical and Experimental Ophthalmology Pub Date : 2024-05-16 DOI:10.1111/ceo.14388

Fang-Yu Chang MD, Chu-Hsuan Huang MD, Chang-Hao Yang MD, PhD, Jung-Tzu Chang MD, Chung-May Yang MD, PhD, Tzzy-Chang Ho MD, Yi-Ting Hsieh MD, PhD, Tso-Ting Lai MD, Chao-Wen Lin MD, Chang-Pin Lin MD, Yi-Chieh Chen MD, Ying-Ju Lai MS, Pei-Lung Chen MD, PhD, Jacob Shujui Hsu PhD, Ta-Ching Chen MD, PhD

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Abstract

Background

To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response.

Methods

This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed.

Results

In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049).

Conclusions

Among the 16 SNPs found in the GWAS, four loci—CFH, ARMS2/HTRA1, and two novel loci—were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

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新生血管性老年性黄斑变性易感性和抗血管内皮生长因子玻璃体内注射治疗反应的遗传学：病例系列研究。

背景为了确定与新生血管性年龄相关性黄斑变性（nAMD）相关的基因型，并研究基因型变异与抗血管内皮生长因子（VEGF）治疗反应之间的关联。方法这项观察性、回顾性、病例系列研究招募了2012年至2020年期间在台湾大学医院接受抗血管内皮生长因子治疗且随访至少一年的确诊为nAMD的患者。研究人员对入选患者和对照组进行了全基因组关联研究（GWAS）。结果共招募了 182 名 nAMD 患者和 1748 名对照者。GWAS发现了16个单核苷酸多态性（SNPs）作为nAMD的风险位点，包括CFH和ARMS2/HTRA1中的7个位点以及9个新的位点、包括 rs117517872 和 rs79835234（COPB2-DT）、rs7525578（RAP1A）、rs2123738（LOC105376755）、rs1374879（CNTN3）、rs3812692（SAR1A）、rs117501587（PRKCA）、rs9965945（CNDP1）和 rs189769231（MATK）。我们的研究发现，rs800292(CFH)、rs11200638(HTRA1)和rs2123738(LOC105376755)分别与VA（P = 0.005）、SRF（P = 0.044）和纤维血管性PED（P = 0.007）的不良治疗反应相关。结论在 GWAS 发现的 16 个 SNPs 中，4 个位点-CFH、ARMS2/HTRA1 和 2 个新位点-与 nAMD 易感性和抗 VEGF 治疗后的解剖/功能反应相关。

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来源期刊

Clinical and Experimental Ophthalmology 医学-眼科学

CiteScore

7.60

自引率

12.50%

发文量

150

审稿时长

4-8 weeks

期刊介绍： Clinical & Experimental Ophthalmology is the official journal of The Royal Australian and New Zealand College of Ophthalmologists. The journal publishes peer-reviewed original research and reviews dealing with all aspects of clinical practice and research which are international in scope and application. CEO recognises the importance of collaborative research and welcomes papers that have a direct influence on ophthalmic practice but are not unique to ophthalmology.