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

Abstract

Purpose: To investigate the relationship of inflammatory biomarkers with corneal epithelial quantifiable metrics in patients with keratoconus and in healthy eyes. Design: Prospective observational comparative study. Participants: This study included 100 eyes of 100 patients: 48 eyes of 48 patients with keratoconus and 52 healthy eyes of 52 healthy controls. Methods: The concentrations of tear cytokines were investigated in both groups: interleukin (IL) 1B, IL6, IL8, IL10, IL12p70, and tumor necrosis factor α (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 OCT. Pearson correlation (r) was used to measure linear dependence between 2 different variables. Main Outcome Measures: Investigating 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. Results: Eyes 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 with 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 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. Conclusions: The 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. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Keywords

• Epithelial map
• Cortisol, Interleukin 6
• Keratoconus