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.

中文翻译：

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年龄相关性黄斑变性中网状假性粉刺的患病率，风险和遗传关联：与年龄有关的眼病研究2报告21。

目的确定具有年龄相关性黄斑变性（AMD）的眼睛中网状假性鼻疽（RPD）的患病率，评估RPD作为AMD晚期发展的独立危险因素的作用，并评估与RPD的遗传关联。设计前瞻性队列研究。参与者一只或两只眼睛中度AMD的参与者参加了与年龄有关的眼病研究2（AREDS2），这是一项为期5年的多中心营养补充剂研究。方法在每年的随访中评估了来自AREDS2参与者的子集的眼底自发荧光（FAF）图像。评估了六个单核苷酸多态性-rs10490924（ARMS2），rs1061170（CFH），rs2230199（C3），rs116503776和rs114254831（C2 / CFB）和rs943080（VEGF-A）-以及与遗传风险评分（GRS）的相关性RPD。晚期AMD的发展，确定了定义为地理萎缩（GA）或新血管性AMD（NVAMD）的患者。主要观察指标RPD的发生率，AMD晚期发育的比值比（OR）和RPD的遗传关联。结果对5021只眼睛（2516名参与者）的FAF图像进行了评估。在1186眼中观察到网状假单眼（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（n = 458）为6％，中级AMD（n = 2606）为26％，GA（n = 682）为36％，NVAMD（n = 19）（n = 1246）。没有RPD的参与者的平均年龄为79岁（标准差[SD]，7）和75岁（SD，8）（P <0.0001）。女性参与者中网状假性肾炎更为常见（RPD为65％，无RPD的为53％）。根据基准年龄，性别，种族，教育程度，吸烟，GA的1710只眼有发生晚期AMD风险的眼睛的AMD严重度水平为GA，为2.42（95％置信区间[CI]，1.80-3.24； P <0.001），而对于GA，为1.21（95％CI，0.87-1.7）；对于NVAMD，P = 0.26）。RPD的存在与更高的GRS（P <0.0001）和ARMS2风险等位基因（P <0.0001）显着相关，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）相关。结论RPD参与者发展为GA的风险增加，但NVAMD没有。ARMS2风险等位基因和较高的GRS与RPD的存在有关。这项研究表明，RPD是重要的危险标志物，应包括在用于患者预后的分类系统中。24; GA的P <0.001）和NVAMD的1.21（95％CI，0.87-1.7; P = 0.26）。RPD的存在与更高的GRS（P <0.0001）和ARMS2风险等位基因（P <0.0001）显着相关，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）相关。结论RPD参与者发展为GA的风险增加，但NVAMD没有。ARMS2风险等位基因和较高的GRS与RPD的存在有关。这项研究表明，RPD是重要的危险标志物，应包括在用于患者预后的分类系统中。24; GA的P <0.001）和NVAMD的1.21（95％CI，0.87-1.7; P = 0.26）。RPD的存在与更高的GRS（P <0.0001）和ARMS2风险等位基因（P <0.0001）显着相关，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）相关。结论RPD参与者发展为GA的风险增加，但NVAMD没有。ARMS2风险等位基因和较高的GRS与RPD的存在有关。这项研究表明，RPD是重要的危险标志物，应包括在用于患者预后的分类系统中。04）和CFH风险等位基因（纯合子P = 0.048）。结论RPD参与者发展为GA的风险增加，但NVAMD没有。ARMS2风险等位基因和较高的GRS与RPD的存在有关。这项研究表明，RPD是重要的危险标志物，应包括在用于患者预后的分类系统中。04）和CFH风险等位基因（纯合子P = 0.048）。结论RPD参与者发展为GA的风险增加，但NVAMD没有。ARMS2风险等位基因和较高的GRS与RPD的存在有关。这项研究表明，RPD是重要的危险标志物，应包括在用于患者预后的分类系统中。