A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss - AREDS Report No. 8
A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss - AREDS Report No. 8
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DOI：
10.1001/archopht.119.10.1417
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发表时间：
2001-10-01
影响因子：
--
通讯作者：
Chew, EY
中科院分区：
文献类型：
--
作者：
Kassoff, A;Kassoff, J;Chew, EY
背景资料：观察和实验数据表明，抗氧化剂和/或锌补充剂可以延缓老年性黄斑变性（AMD）和视力下降的进展。目的：评估高剂量维生素C和E、β胡萝卜素和锌补充剂对AMD进展和视力的影响。设计：AMD相关眼病研究是一项11个中心的双盲临床试验，如果参与者患有广泛的小玻璃疣、中等玻璃疣、大玻璃疣，非中央地图状萎缩，或1只或两只眼睛色素异常，或1只眼睛晚期AMD或由AMD引起的视力丧失。至少1只眼睛的最佳矫正视力为20/32或更好。参与者被随机分配接受每日口服片剂，其中包含：（1）抗氧化剂（维生素C，500 mg;维生素E，400 IU;和β胡萝卜素，15 mg）（2）锌，80 mg，氧化锌和铜，2 mg，氧化铜;（3）抗氧化剂加锌;或（4）安慰剂。主要结局指标：（1）进展为晚期AMD或治疗晚期AMD的照片评估和（2）与基线相比至少中度视力丧失（：15个字母）。主要分析使用重复测量逻辑回归，显著性水平为0.01，未调整协变量。血清水平的测量，病史，死亡率被用于安全monitoring.Results：3640登记的研究参与者，年龄在55-80岁，平均随访6.3年，与2.4%的失访。与安慰剂相比，抗氧化剂加锌组发生晚期AMD的几率显著降低（比值比[OR]，0.72; 99%置信区间[CI]，0.52-0.98）。单独锌和单独抗氧化剂的OR分别为0.75（99% CI，0.55-1.03）和0.80（99% CI，0.59-1.09）。广泛性小玻璃疣、非广泛性中等大小玻璃疣或色素异常的参与者5年内进展为晚期AMD的概率仅为1.3%。当排除这1063名参与者时，降低的几率估计值增加（抗氧化剂加锌：OR，0.66; 99%CI，0.47-0.91;锌：OR，0.71; 99%CI，0.52-0.99;抗氧化剂：OR，0.76; 99%CI，0.55-1.05）。锌和抗氧化剂加锌显着降低了这个高风险组发展为晚期AMD的几率。只有在接受抗氧化剂加锌治疗的患者中，至少中度视力丧失的发生率才有统计学显著性降低（OR，0.73; 99%CI，0.54-0.99）。没有统计学显着的严重不良反应与任何formulation.Conclusions：年龄大于55岁的人应该有散瞳眼科检查，以确定他们的风险发展为先进的AMD。患有广泛的中等大小玻璃疣、至少1个大玻璃疣、1只眼睛或双眼非中央地图状萎缩、或1只眼睛晚期AMD或AMD所致视力丧失，且无禁忌症（如吸烟）的患者，应考虑补充抗氧化剂加锌（如本研究中使用的）。
Background: Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss.Objective: To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity.Design: The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. Main Outcome Measures: (1)Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline ( : 15 letters). Primary analyses used repeated-measures logistic regression with a significance level of .01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring.Results: Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations.Conclusions: Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.