Outcome parameters in studies investigating dry eye disease: A systematic literature review

The development of effective therapeutics for dry eye disease (DED) is challenging due to its complex pathophysiology, heterogeneous patient presentation and the significant failure rate of previous clinical development programs. This underlines the importance of the selection of appropriate endpoints for clinical trials. The presented systematic review retrospectively analyzes the endpoints used in controlled clinical trials in studies of DED. Published clinical trials in the field of DED were reviewed from 2000 to 2023 and the used clinical endpoints were recorded by type and frequency of use. All studies that met the primary keyword search across various databases (PubMed, Embase, The Cochrane Library, Web of Science and Medline) were imported into Rayyan which was used to facilitate the screening process and support the collaboration between the reviewers. 93 876 studies were found of which 33 908 remained after duplicates were removed. All abstracts were screened for eligibility independently by two reviewers. 355 articles remained for full-text review, of which 194 were included in the present systematic review. The most frequently investigated product was topical medicinal products (88 studies), followed by topical lubricants (57 studies) and nutritional supplements (22 studies). Corneal fluorescein staining (45 studies) and the ocular surface disease index (OSDI; 96 studies) were the most frequently used primary objective and subjective outcome parameters. However, a sustainable number of studies failed to show statistically significant differences between treatment and control groups, despite improvements from baseline. Our findings show that corneal fluorescein staining and OSDI are the most frequently used endpoints in clinical studies, although they frequently are not able to detect differences between the treatment and control groups. Therefore, to enhance the efficiency and reliability of DED clinical trials, a consensus on optimal outcome measures is crucial, and the exploration of novel endpoints should be prioritized. PROSPERO Registration Number: CRD42022350817.