Placebo Effects in DED Studies Associated with Women and Lower Baseline Scores

This recent study presented at ARVO found that placebo effects on DED symptoms and signs were substantial and should be accounted for in trial design. It found no predictors for DED signs. Photo: Pam Theriot, OD. Click image to enlarge. Though many clinical trials have been run in the past to address dry eye disease (DED), the placebo effect seen in these trials is poorly understood. Researchers based out of Philadelphia evaluated the presence, magnitude and factors associated with placebo effects in randomized clinical trials of DED to improve future trial design. They determined that these effects were associated with the percent of women in these trial cohorts as well as the baseline symptom severity of participants. The team presented their findings at ARVO 2025 in Salt Lake City last week.Eligible placebo-controlled dry eye trials were identified using PubMed. The study authors independently extracted data for trial characteristics and outcome measures for DED signs (e.g., Schirmer’s test, tear breakup time [TBUT], conjunctival staining, corneal staining) and symptoms (e.g., Ocular Surface Disease Index [OSDI]) for the placebo group. The analysis included 49 eligible trials and 3,529 participants in placebo groups.Meta-analyses revealed significant placebo effects on DED symptoms as measured by OSDI (mean change: -8.44), as well as the signs TBUT (0.50), corneal staining (-0.55) and conjunctival staining (-0.46). Meta-regression found that a higher percentage of female participants and lower baseline scores were independently associated with a greater placebo response for OSDI. The researchers found no significant factors for placebo effects on DED signs.The study authors concluded that future studies should explore mechanisms underlying placebo effects and approaches to mitigate their impact in DED trials.Original abstract content ©2025 Association for Research in Vision and Ophthalmology. Huang AY, Zhang A, Lee D, Ying GS. News Placebo effects on dry eye symptoms and signs in randomized clinical trials of dry eye disease: a systematic review and meta-analysis. ARVO 2025 annual meeting.