Relationship of Inflammatory Mediators (Interleukin and Cortisol Concentrations) with Corneal Epithelial Quantifiable Metrics

Abstract

PurposeTo investigate the relationship of inflammatory biomarkers with corneal epithelial quantifiable metrics in patients with keratoconus and in healthy eyes. DesignProspective observational comparative study. ParticipantsThis study included 100 eyes of 100 patients, 48 eyes of 48 patients with KC, and 52 healthy eyes of 52 healthy controls. MethodsThe concentrations of tear cytokines were investigated in both groups: interleukin (IL) 1B, IL6, IL8, IL10, IL12p70 and TNFα were obtained by capillary flow and measured using flow cytometer. Cortisol concentrations were determined in both groups from the most proximal hair segment as an index of cumulative secretion and measured by liquid chromatography mass spectrometry. Epithelial variables were obtained with optical coherence tomography (OCT). Pearson correlation (r) was used to measure linear dependence between two different variables. Main Outcome MeasuresInvestigating the existence, strength, and significance of any correlation between inflammatory biomarkers (IL1B, IL6, IL8, IL10, IL12p70, TNFα and hair cortisol concentration) and OCT corneal epithelial quantifiable variables such as minimum and maximum epithelial thickness of the map, difference between the minimum and maximum (Epithelial Min-Max) and standard deviation of the epithelial thickness of the map (Epithelial Std Dev) and average epithelial thickness of the superior and inferior regions of the map. ResultsEyes with keratoconus presented statistically significantly higher levels of IL1b (p=0.02), IL6 (p <0.0001), IL8 (p <0.0001), and TNFα (p <0.0001) and hair cortisol concentration (p=0.01) compared to healthy controls.There was a significant correlation between IL6 and measurement Epithelium Min-Max [Pearson= -0.59 (-0.69, -0.47); p<0.0001] and Epithelial standard deviation (Std Dev) [Pearson= +0.56 (0.44, 0.67); p<0.0001]. There was a significant correlation between hair cortisol concentration and Epithelium Min-Max [Pearson=-0.27 (-0.42, -0.1); p<0.0001] and Epithelium Std Dev groups [Pearson= +0.2 (0.03, 0.36); p=0.021]. There was also a significant correlation between TNFα and Epithelial Max. [Pearson= -0.37 (-0.55, 0.17); p<0.0001]. We found no significant correlation between the concentration of IL1b, IL8, IL10 and IL2p70 with any epithelium parameters. ConclusionsThe higher concentration of inflammatory markers (IL6 and hair cortisol) in eyes with keratoconus present a significant correlation with OCT metrics identifying epithelial variability, such as Epithelial Min-Max and Std Dev. These findings demonstrate the role of chronic inflammation in eyes with keratoconus, and that these epithelial changes detectable with OCT are sensitive to this inflammatory process.