Abstract
Purpose :
To determine the magnitude and predictors of the placebo effects on dry eye symptoms and signs in the Dry Eye Assessment and Management (DREAM) study.
Methods :
Secondary analysis of data from the DREAM participants randomized to the placebo group (daily supplement of five soft-gelatin capsules containing 1000 mg of refined olive oil for one year). At baseline, 3, 6, and 12 months, DED symptoms were evaluated using the Ocular Surface Disease Index (OSDI), and DED signs were assessed using conjunctival staining, corneal staining, tear break-up time (TBUT), Schirmer testing, and meibomian gland dysfunction (MGD). Placebo effects were calculated as change from baseline in DED symptoms and signs over 12 months follow-up. Baseline demographics, systemic diseases, DED symptoms, and signs were evaluated as predictors for placebo effects using univariable and multivariable regression models.
Results :
Among the 186 participants in the placebo group, 164 (88%) completed 12-month follow-up. The mean baseline age was 58 years, 82% female, 74% White. There were statistically significant (p<0.001, Table 1) placebo effects on DED symptoms and signs that were evident by 3 months and remained until 12 months as demonstrated by decline (e.g., symptoms improvement) in OSDI total score (mean decline 10.4 points), subscale scores of vision-related functions (mean decline 11.3 points), ocular symptoms (mean decline 10.9 points) and environment trigger (mean decline 8.5 points), improvement in conjunctival staining score (mean decline 0.5 points, p<0.001), corneal staining score (mean decline 0.9 points, p<0.001), tear break-up time (mean increase 0.7 seconds, p<0.001), and MGD (mean decline 0.3 points, p=0.01). In multivariable analyses (Table 2), higher baseline OSDI total score (p<0.001) and absence of rheumatoid arthritis (p=0.01) predicted more improvement in OSDI total score with an R2=0.25. Higher OSDI total score (p=0.01), higher tear break-up time (p=0.002), higher conjunctival staining score (p=0.02), and higher MGD score (p<0.001) at baseline predicted more decline in MGD score with an R2 value of 0.29.
Conclusions :
The DREAM study revealed significant placebo effects on dry eye symptoms and signs, with worse baseline dry eye symptoms and signs predicting a larger placebo effect. Future dry eye clinical trials should consider placebo effects in both trial design and statistical analysis.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.