State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, Guangdong, China.
Centre for Public Health, Queen's University Belfast, Belfast, Belfast, UK.
BMJ. 2024 Sep 11;386:e080474. doi: 10.1136/bmj-2024-080474.
To assess efficacy and safety of laughter exercise in patients with symptomatic dry eye disease.
Non-inferiority randomised controlled trial.
Recruitment was from clinics and community and the trial took place at Zhongshan Ophthalmic Center, Sun Yat-sen University, the largest ophthalmic centre in China, between 18 June 2020 to 8 January 2021.
People with symptomatic dry eye disease aged 18-45 years with ocular surface disease index scores ranging from 18 to 80 and tear film break-up time of eight seconds or less.
Participants were randomised 1:1 to receive laughter exercise or artificial tears (0.1% sodium hyaluronic acid eyedrop, control group) four times daily for eight weeks. The laughter exercise group viewed an instructional video and participants were requested to vocalise the phrases "Hee hee hee, hah hah hah, cheese cheese cheese, cheek cheek cheek, hah hah hah hah hah hah" 30 times per five minute session. Investigators assessing study outcomes were masked to group assignment but participants were unmasked for practical reasons.
The primary outcome was the mean change in the ocular surface disease index (0-100, higher scores indicating worse ocular surface discomfort) from baseline to eight weeks in the per protocol population. The non-inferiority margin was 6 points of this index score. Main secondary outcomes included the proportion of patients with a decrease from baseline in ocular surface disease index score of at least 10 points and changes in dry eye disease signs, for example, non-invasive tear break up time at eight weeks.
299 participants (mean age 28.9 years; 74% female) were randomly assigned to receive laughter exercise (n=149) or 0.1% sodium hyaluronic acid (n=150). 283 (95%) completed the trial. The mean change in ocular surface disease index score at eight weeks was -10.5 points (95% confidence interval (CI) -13.1 to -7.82) in the laughter exercise group and -8.83 (-11.7 to -6.02) in the control group. The upper boundary of the CI for difference in change between groups was lower than the non-inferiority margin (mean difference -1.45 points (95% CI -5.08 to 2.19); P=0.43), supporting non-inferiority. Among secondary outcomes, the laughter exercise was better in improving non-invasive tear break up time (mean difference 2.30 seconds (95% CI 1.30 to 3.30), P<0.001); other secondary outcomes showed no significant difference. No adverse events were noted in either study group.
The laughter exercise was non-inferior to 0.1% sodium hyaluronic acid in relieving subjective symptoms in patients with dry eye disease with limited corneal staining over eight weeks intervention.
ClinicalTrials.gov NCT04421300.
评估笑运动疗法对有症状的干眼患者的疗效和安全性。
非劣效性随机对照试验。
中山大学中山眼科中心，这是中国最大的眼科中心，招募工作于 2020 年 6 月 18 日至 2021 年 1 月 8 日期间在诊所和社区进行。
年龄在 18-45 岁之间、眼表疾病指数评分在 18-80 分之间、泪膜破裂时间在 8 秒或以下的有症状的干眼患者。
参与者以 1:1 的比例随机接受笑运动疗法或人工泪液（0.1% 透明质酸钠滴眼液，对照组），每天四次，持续八周。笑运动疗法组观看教学视频，参与者被要求每五分钟进行 30 次“嘻嘻嘻，哈哈哈，奶酪奶酪奶酪，脸颊脸颊脸颊，哈哈哈哈哈哈”的发声。评估研究结果的调查人员对分组情况不知情，但由于实际原因，参与者是知情的。
主要结局指标是从基线到八周时方案人群中眼表疾病指数（0-100，得分越高表示眼表面不适越严重）的平均变化。非劣效性边界为该指数得分 6 分。主要次要结局包括从基线开始眼表疾病指数评分至少下降 10 分的患者比例以及干眼疾病迹象的变化，例如八周时非侵入性泪膜破裂时间。
299 名参与者（平均年龄 28.9 岁；74%为女性）被随机分配接受笑运动疗法（n=149）或 0.1%透明质酸钠（n=150）。283 名（95%）完成了试验。笑运动疗法组八周时眼表疾病指数评分的平均变化为-10.5 分（95%置信区间[CI]为-13.1 至-7.82），对照组为-8.83 分（-11.7 至-6.02）。组间差异变化的 CI 上限低于非劣效性边界（平均差异-1.45 分[95%CI-5.08 至 2.19]；P=0.43），支持非劣效性。在次要结局中，笑运动疗法在改善非侵入性泪膜破裂时间方面更好（平均差异 2.30 秒[95%CI 1.30 至 3.30]，P<0.001）；其他次要结局无显著差异。两组均未发生不良事件。
在八周的干预期间，笑运动疗法在缓解干眼患者的主观症状方面不劣于 0.1%透明质酸钠，且角膜染色有限。
ClinicalTrials.gov NCT04421300。
