Longitudinal, prospective evaluation of inflammatory tear cytokine ratios and their association with ocular surface disease

PURPOSE: To evaluate longitudinal, prospective associations of pro- and anti-inflammatory tear cytokine ratios with signs of dry eye disease (DED), in young adults. METHODS: Fifty young adults, aged 18 to 25, were recruited; detailed ocular surface parameters were assessed including ocular staining, lid wiper epitheliopathy, ocular redness, and meibomian gland parameters. Tears were collected using Schirmer strips and analysed for ten cytokines using a Luminex Assay. All measures were repeated after 1 year ± 2 months. The ratios of two anti-inflammatory cytokines, IL-10 and IL-1Ra, with four key pro-inflammatory cytokines, IL-1β, IL-6, TNF-α, and IL-8 were investigated and correlations with clinical parameters explored. RESULTS: Participants mean age at baseline was 19.9 ± 1.6 years; 72% females and 56% diagnosed with DED (TFOS DEWS II diagnostic criteria). While IL-1Ra was upregulated at the second visit (p = 0.047), and IL-10, IL-1β, and IL-8 were upregulated at both study visits in dry eye participants (p > 0.05), the anti-to pro-inflammatory cytokine ratios did not distinguish them from the non-DED participants. Certain cytokine ratios, in particular IL-10:IL-6 and IL-10:IL-8, revealed several moderately significant correlations (p < 0.05) with increasing clinical signs of DED; these included horizontal and sagittal lid wiper epitheliopathy, corneal staining, and most notably limbal and bulbar redness, which showed longitudinal repeatability. CONCLUSIONS: Upregulation of both pro- and anti-inflammatory cytokines, and correlation of their ratios with clinical signs, provides support for a coordinated inflammatory network in DED. The correlation of several cytokine ratios with both bulbar and limbal redness and their longitudinal repeatability, suggest ocular redness to be a key consideration in early diagnosis of non-aqueous DED.