Importance Results of several small randomized clinical trials have suggested that supplements of marine ω-3 fatty acids may be beneficial in treating signs and symptoms of dry eye disease (DED). However, randomized clinical trial data to examine whether ω-3 fatty acid supplements can prevent DED are lacking. Objective To evaluate whether long-term daily supplementation with marine ω-3 fatty acids prevents the development of DED. Design, Setting, and Participants This was a prespecified ancillary study of the Vitamin D and Omega-3 Trial (VITAL), a nationwide randomized double-blind placebo-controlled 2 × 2 factorial trial of vitamin D and marine ω-3 fatty acids in the primary prevention of cancer and cardiovascular disease. Participants in this ancillary study were 23 523 US adults (men 50 years and older and women 55 years and older) who at study entry were free of a previous diagnosis of DED and were not experiencing severe dry eye symptoms. Participants were enrolled from November 2011 to March 2014, and treatment and follow-up ended on December 31, 2017. Data were analyzed from January 2020 to August 2021. Interventions Marine ω-3 fatty acids, 1 g per day. Main Outcomes and Measures The primary end point was incident clinically diagnosed DED confirmed by review of the medical records. The secondary end point was a composite of all confirmed incident clinically diagnosed DED cases plus all incident reports of severe DED symptoms. Results The mean (SD) age of the 23 523 participants included in the analysis was 67.0 (7.0) years, and 11 349 participants (48.3%) were women. The cohort included 4610 participants (20.0%) who self-identified as Black, 16 481 (71.6%) who self-identified as non-Hispanic White, and 1927 (8.4%) of other racial or ethnic groups or who declined to respond, consolidated owing to small numbers, including American Indian or Alaska Native, Asian, Hispanic or Latino, and Native Hawaiian or Other Pacific Islander. During a median (range) 5.3 (3.8-6.1) years of treatment and follow-up, 472 of 23 523 participants (2.0%) experienced a medical record-confirmed diagnosis of DED. There was no difference in diagnosed DED by randomized ω-3 fatty acid assignment (232 of 11 757 participants [2.0%] with end points in the treated group vs 240 of 11 766 [2.0%] with end points in the placebo group; hazard ratio, 0.97; 95% CI, 0.81-1.16). Similarly, there was no difference between groups for the secondary end point of diagnosed DED plus incident severe DED symptoms (1044 participants [8.9%] with end points in the treated group vs 1074 [9.1%] with end points in the placebo group; hazard ratio, 0.97; 95% CI, 0.89-1.06). Conclusions and Relevance In this randomized clinical trial, long-term supplementation with 1 g per day of marine ω-3 fatty acids for a median (range) of 5.3 (3.8-6.1) years did not reduce the incidence of diagnosed DED or a combined end point of diagnosed DED or incident severe DED symptoms. These results do not support recommending marine ω-3 fatty acid supplementation to reduce the incidence of DED. Trial Registration ClinicalTrials.gov Identifier: NCT01880463.

中文翻译：

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海洋 ω-3 脂肪酸补充剂与安慰剂在降低健康美国成年人干眼症发病率方面的功效：一项随机临床试验。

重要性 几项小型随机临床试验的结果表明，补充海洋 ω-3 脂肪酸可能有益于治疗干眼病 (DED) 的体征和症状。然而，缺乏检查 ω-3 脂肪酸补充剂是否可以预防 DED 的随机临床试验数据。目的 评估长期每天补充海洋 ω-3 脂肪酸是否能预防 DED 的发展。设癌症和心血管疾病的一级预防。这项辅助研究的参与者是 23,523 名美国成年人（50 岁及以上的男性和 55 岁及以上的女性），他们在研究开始时之前没有被诊断为 DED，并且没有出现严重的干眼症状。参与者于 2011 年 11 月至 2014 年 3 月入组，治疗和随访于 2017 年 12 月 31 日结束。分析了 2020 年 1 月至 2021 年 8 月的数据。干预 海洋 ω-3 脂肪酸，每天 1 克。主要成果和措施 主要终点是通过回顾病历确认的临床诊断为 DED 的事件。次要终点是所有确诊的临床诊断 DED 病例加上所有严重 DED 症状的事件报告的综合。结果 纳入分析的 23 523 名参与者的平均 (SD) 年龄为 67.0 (7.0) 岁，11 349 名参与者 (48. 3%) 是女性。该队列包括 4610 名自认为是黑人的参与者 (20.0%)，16481 名 (71.6%) 自认为是非西班牙裔白人的参与者，以及 1927 名 (8.4%) 其他种族或族裔群体或拒绝回应的人，由于人数少而合并，包括美洲印第安人或阿拉斯加原住民、亚裔、西班牙裔或拉丁裔，以及夏威夷原住民或其他太平洋岛民。在中位（范围）5.3 (3.8-6.1) 年的治疗和随访期间，23523 名参与者中有 472 名 (2.0%) 经历了医疗记录确认的 DED 诊断。通过随机 ω-3 脂肪酸分配诊断的 DED 没有差异（治疗组 11757 名参与者中有 232 名 [2.0%] 有终点，而安慰剂组有终点的 11766 名参与者中有 240 名 [2.0%]；危险比率，0.97；95% CI，0.81-1.16）。相似地，诊断出的 DED 加事件严重 DED 症状的次要终点在组间没有差异（治疗组有 1044 名参与者 [8.9%] 有终点，安慰剂组有 1074 名 [9.1%] 有终点；风险比， 0.97；95% CI，0.89-1.06）。结论和相关性 在这项随机临床试验中，每天补充 1 g 海洋 ω-3 脂肪酸的中位（范围）为 5.3 (3.8-6.1) 年的长期补充并没有降低诊断出的 DED 或合并症的发生率诊断为 DED 的终点或事件严重的 DED 症状。这些结果不支持推荐补充海洋 ω-3 脂肪酸来降低 DED 的发生率。试验注册 ClinicalTrials.gov 标识符：NCT01880463。治疗组有 9%] 有终点，而安慰剂组有 1074 [9.1%] 有终点；风险比，0.97；95% 置信区间，0.89-1.06）。结论和相关性 在这项随机临床试验中，每天补充 1 g 海洋 ω-3 脂肪酸的中位（范围）为 5.3 (3.8-6.1) 年的长期补充并没有降低诊断出的 DED 或合并症的发生率诊断为 DED 的终点或事件严重的 DED 症状。这些结果不支持推荐补充海洋 ω-3 脂肪酸来降低 DED 的发生率。试验注册 ClinicalTrials.gov 标识符：NCT01880463。治疗组有 9%] 有终点，而安慰剂组有 1074 [9.1%] 有终点；风险比，0.97；95% 置信区间，0.89-1.06）。结论和相关性 在这项随机临床试验中，每天补充 1 g 海洋 ω-3 脂肪酸的中位（范围）为 5.3 (3.8-6.1) 年的长期补充并没有降低诊断出的 DED 或合并症的发生率诊断为 DED 的终点或事件严重的 DED 症状。这些结果不支持推荐补充海洋 ω-3 脂肪酸来降低 DED 的发生率。试验注册 ClinicalTrials.gov 标识符：NCT01880463。每天补充 1 克海洋 ω-3 脂肪酸，中位数（范围）为 5.3 (3.8-6.1) 年，并没有降低诊断出的 DED 的发生率或诊断出的 DED 或严重 DED 事件的综合终点症状。这些结果不支持推荐补充海洋 ω-3 脂肪酸来降低 DED 的发生率。试验注册 ClinicalTrials.gov 标识符：NCT01880463。每天补充 1 克海洋 ω-3 脂肪酸，中位数（范围）为 5.3 (3.8-6.1) 年，并没有降低诊断出的 DED 的发生率或诊断出的 DED 或严重 DED 事件的综合终点症状。这些结果不支持推荐补充海洋 ω-3 脂肪酸来降低 DED 的发生率。试验注册 ClinicalTrials.gov 标识符：NCT01880463。