Abstract
Purpose :
To test the association between serum inflammatory markers and dry eye disease (DED) using a hypothesis-free proteomic approach in a longitudinal population study.
Methods :
A total of 2602 unselected community-based participants (mean age 61.5 (range 17-92 years), 94.4% female) in the TwinsUK cohort from across the United Kingdom were included. Dry eye disease was assessed with the validated Women’s Health Study (WHS) questionnaire at three time points in 2010, 2013 and 2017. Cases were defined by either a previous diagnosis of DED by a clinician or the presence of highly symptomatic dry eye at any of these time points. Serum inflammatory markers were assessed with the Olink Target 96 Inflammation protein biomarker panel, following standard procedures. Association analyses were performed with logistic regression mixed effect models that included age, BMI, family and sex as covariates, corrected for multiple testing using a false discovery rate approach.
Results :
Prevalence of WHS-defined DED was 30.1%, with 26.2% having a previous diagnosis of DED and 11.5% having highly symptomatic dry eye. A total of 74 inflammatory markers were included in the analysis after quality control. After strict correction for multiple testing, no significant associations with serum inflammatory markers were found for WHS-defined DED or a clinical diagnosis. Suggestive associations for WHS-defined DED that almost reached statistical significance were found for neurotrophin-3 (unadjusted P=0.0008), natural killer-cell receptor 2B4 (CD244) (P=0.003), C-X-C motif chemokine (CXCL) 9 (P=0.002), and CXCL10 (P=0.003). Strong and significant associations with highly symptomatic dry eye were found with increased levels of the markers CXCL10 (P=0.0003) , CXCL9 (P=0.0005), C-C motif chemokine (CCL) 19 (P=0.0009), and CCL20 (P=0.001). Other suggestive associations with highly symptomatic dry eye were found for interleukin-8 (IL-8) (P=0.004), CCL25 (P=0.006), programmed cell death 1 ligand 1 (PD-L1) (P=0.008), and tumor necrosis factor receptor superfamily member 9 (TNFRSF9) (P=0.009).
Conclusions :
This large population-based study found several serum inflammatory proteins are biomarkers for dry eye. This confirms and adds to previous targeted tear and corneal and conjunctival expression studies in murine models and clinic-based case-control studies. In addition, novel potential biomarkers were identified.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.