Dry eye disease (DED) can be extremely distressing and is common in type 2 diabetes (T2D). To investigate potential biomarkers of DED in T2D, panels of proteins in tears, alongside clinical signs and symptoms of DED, were assessed. Patients were classified into four groups: T2D + DED (n = 47), T2D-only (n = 41), DED-only (n = 17) and healthy controls (n = 17). All patients underwent the Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality of Life (DEQS) questionnaires, tear evaporation rate (TER), fluorescein tear break-up time (fTBUT), corneal fluorescein staining (CFS) and Schirmer 1 test assessments. Six metabolic proteins and 14 inflammatory cytokines were analyzed with multiplex bead analysis. Interleukin (IL)-6 and IL-8 concentrations in tears were significantly higher in the T2D + DED group, and these biomarkers were positively correlated with CFS. In addition, tear IL-6 was negatively correlated with fTBUT in the T2D + DED group. Clinical signs of DED in the T2D + DED group were similar to the DED-only group. The T2D + DED group had more patients with moderate and severe DED (versus the DED-only group), suggesting a different pathogenesis for DED in T2D versus DED-only. Therefore, IL-6 and IL-8 could potentially be diagnostic biomarkers of DED in T2D.

The concentrations of insulin, leptin, active ghrelin, C-peptide and gastric inhibitory polypeptide (GIP) and their inter-day variations were examined in normal human tears. In addition, correlations between the concentrations of these metabolic proteins and ocular surface parameters were determined. Subjects with healthy ocular surfaces attended three visits, with 7-day intervals. Tear evaporation rate (TER) and non-invasive tear break-up time (NITBUT) were assessed, and a total of 2 µL tears were collected from all subjects. Tear fluid concentrations of insulin, leptin, active ghrelin, C-peptide and GIP were measured by multiplex bead analysis. Insulin was the most highly expressed metabolic protein, followed by leptin, C-peptide, active ghrelin and GIP. Of these, only active ghrelin had a significant inter-day variation (p < 0.05). There was no inter-day variation in the mean concentrations of the other metabolic proteins. Leptin had a strong intra-class reproducibility. No correlation was detected between tear metabolic protein concentrations and ocular surface parameters. This pilot study shows, for the first time, that active ghrelin and GIP are detectable in healthy tears. The strong intra-class reproducibility for leptin shows that it could be used as a potential tear fluid biomarker and, possibly, in determining the effects of metabolic disorders on the ocular surface.

Dry eye disease (DED) can be extremely distressing and is common in type 2 diabetes (T2D). To investigate potential biomarkers of DED in T2D, panels of proteins in tears, alongside clinical signs and symptoms of DED were assessed. Patients were classified into four groups: T2D+DED (n=47), T2D-only (n=41), DED-only (n=17) and healthy controls (n=17). All patients underwent the Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality of Life (DEQS) questionnaires, tear evaporation rate (TER), fluorescein tear break-up time (fTBUT), corneal fluorescein staining (CFS) and Schirmer 1 test assessments. Six metabolic proteins and 14 inflammatory cytokines were analyzed with multiplex bead analysis. Interleukin (IL)-6 and IL-8 concentrations in tears were significantly higher in the T2D+DED group and these biomarkers were positively correlated with CFS. In addition, tear IL-6 was negatively correlated with fTBUT in the T2D+DED group. Clinical signs of DED in the T2D+DED group were similar to the DED-only group. The T2D+DED group had more patients with moderate and severe DED (versus the DED-only group), suggesting a different pathogenesis for DED in T2D versus DED-only. Therefore, IL-6 and IL-8 could potentially be diagnostic biomarkers of DED in T2D.