Prevalence, Risk, and Genetic Association of Reticular Pseudodrusen in Age-related Macular Degeneration
Prevalence, Risk, and Genetic Association of Reticular Pseudodrusen in Age-related Macular Degeneration
复制标题
DOI：
10.1016/j.ophtha.2019.07.022
复制
发表时间：
2019-12-01
期刊：
影响因子：
13.7
通讯作者：
Chew, Emily Y.
中科院分区：
文献类型：
--
作者：
Domalpally, Amitha;Agron, Elvira;Chew, Emily Y.
目的：确定年龄相关性黄斑变性（AMD）患者视网膜网状假性玻璃疣（RPD）的患病率，评估RPD作为晚期AMD发展的独立危险因素的作用，并评估与RPD的遗传相关性。设计：前瞻性队列研究。单眼或双眼患有中度AMD的参与者参加了AMD相关眼病研究2（AREDS 2），一项为期5年的多中心营养补充剂研究。方法：在每年的访视中评估来自AREDS 2参与者子集的眼底自体荧光（FAF）图像是否存在RPD。6个单核苷酸多态性-rs 10490924（ARMS 2），rs 1061170（CFH），rs 2230199（C3），rs 116503776和rs 114254831（C2/CFB），rs 943080（VEGF-A）-和遗传风险评分（GRS）与RPD的关联进行了评估。晚期AMD的发展，定义为地图状萎缩（GA）或新生血管性AMD（NVAMD），被identified.Main结果Measures：RPD的患病率，优势比（OR）的晚期AMD的发展，和RPD的遗传associations.Results：FAF图像进行了评价5021眼（2516名参与者）。在1186只眼睛中观察到网状假性玻璃疣（24%的眼睛，29%的参与者）。RPD的患病率随基线AREDS AMD严重程度而变化：早期AMD为6%（n = 458），中期AMD为26%（n = 2606），GA为36%（n = 682），NVAMD为19%（n = 1246）。RPD患者的平均年龄为79岁（标准差[SD]，7），无RPD患者的平均年龄为75岁（SD，8）（P < 0.0001）。网状假性玻璃疣在女性参与者中更常见（65% RPD vs. 53%无RPD）。对于1710只在下一次年度访视时有发生晚期AMD风险的眼睛，根据基线年龄、性别、种族、教育状况、吸烟和AMD严重程度调整后的比值比，GA为2.42（95%置信区间[CI]，1.80-3.24; P < 0.001），NVAMD为1.21（95% CI，0.87-1.7; P = 0.26）。RPD的存在与较高的GRS（P < 0.0001）和ARMS 2风险等位基因（P < 0.0001）显著相关，在名义水平上，与C3风险等位基因（P = 0.04）和CFH风险等位基因（纯合子P = 0.048）显著相关。ARMS 2危险等位基因和较高的GRS与RPD的存在相关。这项研究表明，RPD是一个重要的风险标志物，应包括在用于患者预后的分类系统。(C)2019年美国眼科学会
Purpose: To determine the prevalence of reticular pseudodrusen (RPD) in eyes with age-related macular degeneration (AMD), assess the role of RPD as an independent risk factor for late AMD development, and evaluate genetic association with RPD.Design: Prospective cohort study.Participants: Participants with intermediate AMD in 1 or both eyes enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a 5-year multicenter study of nutritional supplement.Methods: Fundus autofluorescence (FAF) images from a subset of AREDS2 participants were evaluated at annual visits for presence of RPD. Six single nucleotide polymorphisms-rs10490924 (ARMS2), rs1061170 (CFH), rs2230199 (C3), rs116503776 and rs114254831 (C2/CFB), and rs943080 (VEGF-A)-and the genetic risk score (GRS) were assessed for association with RPD. Development of late AMD, defined as geographic atrophy (GA) or neovascular AMD (NVAMD), was identified.Main Outcome Measures: Prevalence of RPD, odds ratio (OR) of late AMD development, and genetic associations of RPD.Results: The FAF images were evaluated for 5021 eyes (2516 participants). Reticular pseudodrusen were seen in 1186 eyes (24% of eyes, 29% of participants). Prevalence of RPD varied with baseline AREDS AMD severity level: 6% in early AMD (n = 458), 26% in intermediate AMD (n = 2606), 36% in GA (n = 682), and 19% in NVAMD (n = 1246). Mean age of participants with RPD was 79 years (standard deviation [SD], 7) and 75 years (SD, 8) in those without RPD (P < 0.0001). Reticular pseudodrusen were more frequent in female participants (65% RPD vs. 53% no RPD). Odds ratio adjusted for baseline age, gender, race, educational status, smoking, and AMD severity level for 1710 eyes at risk of developing late AMD at the next annual visit was 2.42 (95% confidence interval [CI], 1.80-3.24; P < 0.001) for GA and 1.21 (95% CI, 0.87-1.7; P = 0.26) for NVAMD. Presence of RPD was significantly associated with higher GRS (P < 0.0001) and ARMS2 risk alleles (P < 0.0001) and, at a nominal level, with C3 risk alleles (P = 0.04) and CFH risk alleles (P = 0.048 for homozygotes).Conclusions: Participants with RPD have an increased risk of progression to GA but not NVAMD. ARMS2 risk alleles and higher GRS were associated with the presence of RPD. This study suggests that RPD are an important risk marker and should be included in classification systems used for patient prognosis. (C) 2019 by the American Academy of Ophthalmology