Cytokine upregulation and ocular surface dysbiosis in lacrimal drainage pathway disease and its associated keratopathy: a prospective multicenter observational study

Abstract

Abstract Background To elucidate the pathogenesis of lacrimal drainage pathway disease-associated keratopathy (LDAK), we investigated the cytokine profile in tear fluid and the ocular surface microbiome in patients with lacrimal duct disorders. Methods This multi-center prospective study enrolled patients with dacryocystitis or lacrimal duct obstruction treated between January 2020 and March 2023. Tear fluid cytokines from 25 samples from affected and contralateral eyes each were analyzed using a multiplex bead assay. Affected eyes were classified into severe ( n = 17) and non-severe ( n = 8) groups. In 12 eyes, samples were re-collected 3 months after lacrimal tube insertion. The conjunctival sac microbiota from 27 samples from affected eyes were analyzed using 16S rRNA gene sequencing. Alpha and beta diversity were evaluated using the Kruskal–Wallis test and PERMANOVA, respectively. Results Inflammatory cytokines, including IL-1β, IL-6, IL-8, TNF-α, MIP-1β, and MCAF, were significantly elevated in affected eyes compared with contralateral eyes (all P < 0.01). These levels were significantly higher in severe cases than in non-severe cases (all P < 0.05) and decreased significantly following lacrimal duct tube insertion (all P < 0.05). Microbiome analysis revealed that both alpha and beta diversity were significantly increased in affected eyes (Faith’s PD P < 0.001 and PERMANOVA P < 0.001, respectively); however, these alterations resolved and returned to a normal state following surgical treatment. Conclusions Lacrimal duct disorders were associated with increased cytokine expression and altered microbiome composition on the ocular surface, which may be associated with the development of LDAK. The normalization of both the immune environment and microbiota following surgical intervention suggests that interactions between the immune system and the microbiome play a critical role in the clinical course of LDAK.