Abstract:AIM: To investigate the efficacy and mechanisms of indirect intense pulsed light (IPL) irradiation on meibomian gland dysfunction (MGD). METHODS: A total of 60 MGD patients was included in this prospective randomized controlled trial. Patients were randomly assigned 1:1 into two groups (3-mm group and 10-mm group) in which IPL was applied at distances from the lower eyelid margin of 3 and 10 mm, respectively. Both groups received three times treatment with 3-week interval. Meibomian gland yield secretion score (MGYSS), standard patient evaluation of eye dryness (SPEED) questionnaire, tear break-up time (TBUT), corneal fluorescein staining (CFS), and in vivo confocal microscopy were performed at baseline and after every treatment. RESULTS: After three IPL treatments, both groups had significant improvement in MGYSS (both P<0.05). The non-inferiority test showed that improvement in 10-mm group was not inferior to that in 3-mm group (P<0.001). In both groups, temporal regions of both upper and lower eyelids showed significant improvement in MGYSS. Scores of SPEED questionnaire in both groups declined significantly (both P<0.001) and changes of SPEED had no difference between two groups (P=0.57). Density of central corneal subepithelial nerves and TBUTs showed no statistically significant changes. The 3-mm group had improvement on corneal fluorescein staining (P=0.048) and meibomian gland morphology (acini wall thickness P=0.003, hyperreflective points P=0.024) while the 10-mm group had not. CONCLUSION: The efficacy of IPL indirect irradiation in improving meibomian gland secretion and alleviating dry eye symptoms remains unchanged with increase in treatment distance. IPL may primarily act on the functional improvement of the meibomian glands and corneal nerves.