Alan Huang, Annie Zhang, Daniel Lee, Gui-Shuang Ying
{"title":"随机对照试验中安慰剂或载体对干眼体征和症状的影响:一项系统回顾和荟萃分析","authors":"Alan Huang, Annie Zhang, Daniel Lee, Gui-Shuang Ying","doi":"10.1016/j.survophthal.2025.08.014","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Dry eye disease (DED) is one of the most prevalent ophthalmic conditions. Placebo or vehicle administration is frequently used in DED trials, yet its effects remain poorly characterized. This study evaluates the presence, magnitude, and factors associated with DED vehicle or placebo effects to inform future trial design.Eligible vehicle- or placebo-controlled dry eye trials were identified using PubMed. Three authors independently extracted trial characteristics and outcome measures, including Schirmer test, tear breakup time (TBUT), conjunctival and corneal staining, and Ocular Surface Disease Index (OSDI). Random-effect models and meta-regression were used to evaluate placebo/vehicle effects and predictors. Forty-nine trials with 3529 participants in placebo/vehicle groups were included. Meta-analyses revealed significant placebo/vehicle effects on DED symptoms measured by OSDI (mean difference: -8.44; 95 % CI: -11.56 to -5.33, p < 0.01) and on signs including TBUT (0.50; 95 % CI: 0.13-0.87, p = 0.01), corneal staining (-0.55; 95 % CI: -0.90 to -0.20, p < 0.01), and conjunctival staining (-0.46; 95 % CI: -0.91 to -0.02, p = 0.04). Meta-regression revealed that a higher percentage of female participants and worse baseline OSDI scores were associated with a greater vehicle or placebo responses for OSDI (p = 0.04 and p = 0.001, respectively). No predictors were found for placebo/vehicle effects on DED signs. Placebo/vehicle effects in DED trials are substantial and should be considered in trial design. Female sex and worse baseline symptoms were associated with larger effects on OSDI. Future studies should explore mechanisms underlying these effects and approaches to mitigate their impact in DED trials.</p>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":" ","pages":""},"PeriodicalIF":5.9000,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Placebo or vehicle effects on dry eye signs and symptoms in randomized controlled trials: A systematic review and meta-analysis.\",\"authors\":\"Alan Huang, Annie Zhang, Daniel Lee, Gui-Shuang Ying\",\"doi\":\"10.1016/j.survophthal.2025.08.014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Dry eye disease (DED) is one of the most prevalent ophthalmic conditions. Placebo or vehicle administration is frequently used in DED trials, yet its effects remain poorly characterized. This study evaluates the presence, magnitude, and factors associated with DED vehicle or placebo effects to inform future trial design.Eligible vehicle- or placebo-controlled dry eye trials were identified using PubMed. Three authors independently extracted trial characteristics and outcome measures, including Schirmer test, tear breakup time (TBUT), conjunctival and corneal staining, and Ocular Surface Disease Index (OSDI). Random-effect models and meta-regression were used to evaluate placebo/vehicle effects and predictors. Forty-nine trials with 3529 participants in placebo/vehicle groups were included. Meta-analyses revealed significant placebo/vehicle effects on DED symptoms measured by OSDI (mean difference: -8.44; 95 % CI: -11.56 to -5.33, p < 0.01) and on signs including TBUT (0.50; 95 % CI: 0.13-0.87, p = 0.01), corneal staining (-0.55; 95 % CI: -0.90 to -0.20, p < 0.01), and conjunctival staining (-0.46; 95 % CI: -0.91 to -0.02, p = 0.04). Meta-regression revealed that a higher percentage of female participants and worse baseline OSDI scores were associated with a greater vehicle or placebo responses for OSDI (p = 0.04 and p = 0.001, respectively). No predictors were found for placebo/vehicle effects on DED signs. Placebo/vehicle effects in DED trials are substantial and should be considered in trial design. Female sex and worse baseline symptoms were associated with larger effects on OSDI. Future studies should explore mechanisms underlying these effects and approaches to mitigate their impact in DED trials.</p>\",\"PeriodicalId\":22102,\"journal\":{\"name\":\"Survey of ophthalmology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2025-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Survey of ophthalmology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.survophthal.2025.08.014\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Survey of ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.survophthal.2025.08.014","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Placebo or vehicle effects on dry eye signs and symptoms in randomized controlled trials: A systematic review and meta-analysis.
Purpose: Dry eye disease (DED) is one of the most prevalent ophthalmic conditions. Placebo or vehicle administration is frequently used in DED trials, yet its effects remain poorly characterized. This study evaluates the presence, magnitude, and factors associated with DED vehicle or placebo effects to inform future trial design.Eligible vehicle- or placebo-controlled dry eye trials were identified using PubMed. Three authors independently extracted trial characteristics and outcome measures, including Schirmer test, tear breakup time (TBUT), conjunctival and corneal staining, and Ocular Surface Disease Index (OSDI). Random-effect models and meta-regression were used to evaluate placebo/vehicle effects and predictors. Forty-nine trials with 3529 participants in placebo/vehicle groups were included. Meta-analyses revealed significant placebo/vehicle effects on DED symptoms measured by OSDI (mean difference: -8.44; 95 % CI: -11.56 to -5.33, p < 0.01) and on signs including TBUT (0.50; 95 % CI: 0.13-0.87, p = 0.01), corneal staining (-0.55; 95 % CI: -0.90 to -0.20, p < 0.01), and conjunctival staining (-0.46; 95 % CI: -0.91 to -0.02, p = 0.04). Meta-regression revealed that a higher percentage of female participants and worse baseline OSDI scores were associated with a greater vehicle or placebo responses for OSDI (p = 0.04 and p = 0.001, respectively). No predictors were found for placebo/vehicle effects on DED signs. Placebo/vehicle effects in DED trials are substantial and should be considered in trial design. Female sex and worse baseline symptoms were associated with larger effects on OSDI. Future studies should explore mechanisms underlying these effects and approaches to mitigate their impact in DED trials.
期刊介绍:
Survey of Ophthalmology is a clinically oriented review journal designed to keep ophthalmologists up to date. Comprehensive major review articles, written by experts and stringently refereed, integrate the literature on subjects selected for their clinical importance. Survey also includes feature articles, section reviews, book reviews, and abstracts.