Placebo administration for dry eye disease: a level I evidence based systematic review and meta-analysis

Abstract

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.

Effects of Carboxymethylcellulose Artificial Tears on Ocular Surface Microbiome Diversity and Composition, A Randomized Controlled Trial

“… 58 Considering that few of our participants had DES and OSDI reductions were small, the Hawthorne effect may also have resulted in study bias. 59 Our study also had no objective measures for DES such as Schirmer's test, tear breakup time, or tear osmolarity to confirm reduction of DES signs.…”

Chloroquine and Hydroxychloroquine in the Treatment of Dry Eye Disease

“…However, artificial tears only yield symptomatic improvement and do not treat the underlying pathomechanism of the disease, involving inflammation of the ocular surface [19]. The efficacy of various topical anti-inflammatory agents, such as corticosteroids, lifitegrast, and cyclosporine in the treatment of dry eye disease compared against placebo has been shown in previous studies [20][21][22][23]. Additionally, the efficacy and feasibility of a range of complementary medicines in patients with dry eye disease has been demonstrated, including herbal and natural products [24,25], honey [24,26], or acupuncture [24,27].…”