Placebo Administration for Dry Eye Disease: a Level I Evidence Based Systematic Review and Meta-analysis

Background: The efficacy of various common treatment options for dry eye disease (DED) has been investigated against placebo. However, the potential beneficial effect of placebo in the management of DED is still unclear.

Aim: This meta-analysis investigated the impact of placebo administration in DED in Ocular Surface Disease Index (OSDI), Schirmer I test (SIT), tear breakup time (TBUT), corneal staining, and complications.

Method: This meta-analysis and systematic review was conducted according to the 2020 PRISMA guidelines. In March 2022, Pubmed, Web of Science, Google Scholar, and Embase were accessed. All the randomised clinical trials which investigated any active treatment against a placebo control group were considered. The following data were extracted at baseline and at last follow-up: Ocular Surface Disease Index (OSDI), tear breakup time test (TBUT), Schirmer I test (SIT), corneal staining.

Results: Data from 56 studies (12,205 patients) were retrieved. Placebo administration is not effective in improving TBUT (P = 0.3), OSDI (P = 0.2), SIT (P = 0.1) and corneal staining (P = 0.1) from baseline to last follow-up. Active treatment led to a higher TBUT and SIT compared to placebo administration (P < 0.0001). The active treatment resulted in a lower OSDI compared to placebo administration (P = 0.0005). Five studies reported data on the corneal staining. No difference was found between placebo administration and active treatment (P = 0.8).

Conclusion: Placebo administration does not impact symptoms of DED and can be successfully employed to evaluate the efficacy of active treatments.