Intense Pulsed Light Therapy to Inhibit Meibomian Gland Inflammation: Untargeted Metabolomics Analysis of Meibomian Gland Secretions

Objective: To assess the inhibitory effects of intense pulsed light (IPL) on meibomian gland (MG) inflammation. Background: IPL treatment is effective for dry eye disease (DED) caused by meibomian gland dysfunction (MGD). However, the anti-inflammatory and regeneration stimulating effects of IPL on MGD remain unclear. Moreover, studies on inflammatory metabolites in MG secretions are lacking. Methods: Six patients with DED were administered two IPL treatments. Ocular surface disease index (OSDI) questionnaires were used to assess DED, MGD signs, including degree of obstruction, secretion, and atrophy of the MG, tear film break-up time (TBUT) was assessed before and after treatments. To determine IPL treatment-induced changes in metabolites, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze MG secretions. Results: Data were gathered before the first treatment (time A) and 2 weeks after the second treatment (time B). Average OSDI score showed a significant decrease (time A and B measurements were 44.07 and 16.65, respectively). Besides, statistically significant differences were observed in MG signs before and after treatments: degree of obstruction improved and secretions became thinner. TBUT was significantly increased to the normal range. LC-MS/MS led to the identification of 53 differential metabolites: 23 were upregulated (e.g., estradiol, coenzyme Q, and azelaic acid) and 30 were downregulated (e.g., prostaglandins, 20-hydroxyeicosatetraenoic acid, and arachidonic acid). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that most differential metabolites were involved in steroid hormone biosynthesis. Conclusions: Periorbital IPL treatment can improve chronic inflammation of the MG and promote its normal secretion. The steroid hormone biosynthetic pathways may be activated to participate in this anti-inflammatory effect.