Efficacy of topical mesenchymal stem cell exosome in Sjögren's syndrome-related dry eye: a randomized clinical trial.

BACKGROUND: Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder affecting salivary and lacrimal glands, leading to distressing ocular symptoms. Existing therapeutic approaches for SS-associated dry eye syndrome (DES) show insufficient efficacy. This study investigates the use of topical MSC-derived exosomes in primary SS-related DES. METHODS: In phase 1 and 2, triple-blinded, randomized trial, two vials of eye drops are given to each participant, one with code A and one with code B and only the supervisor knows the content of each vial. The treatment group (n = 8 eyes) received 10 µg of MSC-derived exosomes twice daily for two weeks and the control group (n = 8 eyes) received Phosphate buffered saline(PBS) for their respective eyes. Safety was assessed through ophthalmic exams, while DES assessment tests evaluated treatment effectiveness. Non-parametric tests employed to examine assumptions. The differences of ocular examination results between day 0 and month 3 were analyzed using a paired Student's t test. Measurement data that were not normally distributed are represented by the median (interquartile range), and comparisons were performed using the Wilcoxon rank-sum test. RESULTS: The treatment showed promising results, with significant improvements observed in various indicators such as reduced Ocular Surface Disease Index scores, increased tear secretion, lower fluorescein scores, and longer tear-film break-up time before and after treatment and between the controls and the treated groups. Our results showed a significant increase in multifunctional proteins such as Epidermal Growth Factor and thrombospondin-1 and conversely, the levels of pro-inflammatory cytokines, including interleukin-6 and Matrix metalloproteinase-9 significantly decreased in tear of participant before and after treatment and between the controls and the treated groups. CONCLUSIONS: Our study underscores the safety and substantial therapeutic potential of using MSC-derived extracellular exosomes eye drops to treat SS-associated DES. TRIAL REGISTRATION: IRCT20211102052948N1 The study protocol has been approved in Iranian Registry of Clinical Trials at 2022-04-20.