Importance After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up. Objective To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD). Design, Setting, and Participants This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022. Interventions During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively. Main Outcomes and Measures Self-reported lung cancer and late AMD validated with medical records. Results This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48). Conclusions and Relevance Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.

中文翻译：

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在 AREDS 补充剂中添加叶黄素/玉米黄质和 ω-3 脂肪酸对年龄相关性黄斑变性进展的长期结果：AREDS2 报告 28。

重要性 在年龄相关性眼病研究 2 (AREDS2) 研究之后，β-胡萝卜素成分被叶黄素/玉米黄质取代，用于开发修订的 AREDS 补充剂。然而，尚不清楚在 AREDS2 试验结束后，在那些指定的 β 胡萝卜素中观察到的肺癌风险增加是否持续存在，以及在长期服用可观察到的原始 AREDS 补充剂中添加叶黄素/玉米黄质是否有益跟进。目的 评估患肺癌和晚期年龄相关性黄斑变性 (AMD) 的 10 年风险。设计、设置和参与者 这是 AREDS2 临床试验的多中心流行病学随访研究，于 2012 年 12 月 1 日至 2018 年 12 月 31 日进行。分析中包括在临床试验后额外 5 年患有双侧或单侧中间性 AMD 的参与者。在晚期 AMD 发展、死亡或失访时对眼睛/参与者进行审查。分析了 2019 年 11 月至 2022 年 3 月的数据。干预 在临床试验期间，参与者被随机分配到叶黄素/玉米黄质和/或 ω-3 脂肪酸组或安慰剂组，其次是无 β 胡萝卜素组与 β 胡萝卜素组，以及低剂量与高剂量锌。在流行病学后续研究中，所有参与者都接受了含有叶黄素/玉米黄质、维生素 C 和 E 以及锌加铜的 AREDS2 补充剂。在 6 个月的电话中评估结果。使用比例风险回归和逻辑回归分析 AMD 进展和肺癌发展，分别。主要结果和措施 自我报告的肺癌和晚期 AMD 通过医疗记录进行验证。结果 本研究包括 3882 名参与者（平均 [SD] 基线年龄，72.0 [7.7] 岁；2240 名女性 [57.7%]）和 6351 只眼睛。在 10 年时，随机分配给 β 胡萝卜素的患者患肺癌的比值比 (OR) 为 1.82（95% CI，1.06-3.12；P = .02）和 1.15（95% CI，0.79-1.66；P = .46) 用于叶黄素/玉米黄质。将叶黄素/玉米黄质与无叶黄素/玉米黄质进行比较，进展为晚期 AMD 的风险比 (HR) 为 0.91（95% CI，0.84-0.99；P = .02），并且比较 ω-3 脂肪酸与无 ω-3 脂肪酸为 1.01（95% CI，0.93-1.09；P = .91）。当叶黄素/玉米黄质主效应分析仅限于随机分配给 β 胡萝卜素的那些人时，HR 为 0.80（95% CI，0.68-0.92；P = .002）。叶黄素/玉米黄质与 β 胡萝卜素的直接分析显示，晚期 AMD 的 HR 为 0.85（95% CI，0.73-0.98；P = .02）。低锌与高锌的 HR 为 1.04（95% CI，0.94-1.14；P = .49），无 β 胡萝卜素与 β 胡萝卜素的 HR 为 1.04（95% CI，0.94-1.15；P = .48） . 这项针对 AREDS2 队列的长期流行病学随访研究的结论和相关性结果表明，叶黄素/玉米黄质是 AREDS2 补充剂中 β 胡萝卜素的适当替代品。β-胡萝卜素的使用几乎使患肺癌的风险增加了一倍，而叶黄素/玉米黄质的风险没有统计学显着增加。与 β 胡萝卜素相比，叶黄素/玉米黄质与晚期 AMD 进展具有潜在的有益关联。低锌与高锌的 HR 为 1.04（95% CI，0.94-1.14；P = .49），无 β 胡萝卜素与 β 胡萝卜素的 HR 为 1.04（95% CI，0.94-1.15；P = .48） . 这项针对 AREDS2 队列的长期流行病学随访研究的结论和相关性结果表明，叶黄素/玉米黄质是 AREDS2 补充剂中 β 胡萝卜素的适当替代品。β-胡萝卜素的使用几乎使患肺癌的风险增加了一倍，而叶黄素/玉米黄质的风险没有统计学显着增加。与 β 胡萝卜素相比，叶黄素/玉米黄质与晚期 AMD 进展具有潜在的有益关联。低锌与高锌的 HR 为 1.04（95% CI，0.94-1.14；P = .49），无 β 胡萝卜素与 β 胡萝卜素的 HR 为 1.04（95% CI，0.94-1.15；P = .48） . 这项针对 AREDS2 队列的长期流行病学随访研究的结论和相关性结果表明，叶黄素/玉米黄质是 AREDS2 补充剂中 β 胡萝卜素的适当替代品。β-胡萝卜素的使用几乎使患肺癌的风险增加了一倍，而叶黄素/玉米黄质的风险没有统计学显着增加。与 β 胡萝卜素相比，叶黄素/玉米黄质与晚期 AMD 进展具有潜在的有益关联。这项针对 AREDS2 队列的长期流行病学随访研究的结论和相关性结果表明，叶黄素/玉米黄质是 AREDS2 补充剂中 β 胡萝卜素的适当替代品。β-胡萝卜素的使用几乎使患肺癌的风险增加了一倍，而叶黄素/玉米黄质的风险没有统计学显着增加。与 β 胡萝卜素相比，叶黄素/玉米黄质与晚期 AMD 进展具有潜在的有益关联。这项针对 AREDS2 队列的长期流行病学随访研究的结论和相关性结果表明，叶黄素/玉米黄质是 AREDS2 补充剂中 β 胡萝卜素的适当替代品。β-胡萝卜素的使用几乎使患肺癌的风险增加了一倍，而叶黄素/玉米黄质的风险没有统计学显着增加。与 β 胡萝卜素相比，叶黄素/玉米黄质与晚期 AMD 进展具有潜在的有益关联。