Santhiago Marcony R, Stival Larissa R, Araujo Daniella C, Antunes-Foschini Rosalia, Toledo Marcia C, Nunes Ianne L S, Morgado Claudia R, Kara-Junior Newton
Department of Ophthalmology at University of Sao Paulo, Sao Paulo, Brazil.
Department of Ophthalmology at Federal University of Goias, Goiania, Brazil.
Ophthalmol Sci. 2024 Sep 19;5(1):100624. doi: 10.1016/j.xops.2024.100624. eCollection 2025 Jan-Feb.
To investigate the relationship of inflammatory biomarkers with corneal epithelial quantifiable metrics in patients with keratoconus and in healthy eyes.
Prospective observational comparative study.
This study included 100 eyes of 100 patients: 48 eyes of 48 patients with keratoconus and 52 healthy eyes of 52 healthy controls.
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.
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.
Eyes with keratoconus presented statistically significantly higher levels of IL1b ( = 0.02), IL6 ( < 0.0001), IL8 ( < 0.0001), and TNFα ( < 0.0001) and hair cortisol concentration ( = 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); < 0.0001] and Epithelial Std Dev (Pearson = +0.56 [0.44, 0.67]; < 0.0001). There was a significant correlation between hair cortisol concentration and Epithelium Min-Max (Pearson = -0.27 [-0.42, -0.1]; < 0.0001]) and Epithelium Std Dev groups (Pearson = +0.2 [0.03, 0.36]; = 0.021). There was also a significant correlation between TNFα and Epithelial Max (Pearson = -0.37 [-0.55, 0.17]; < 0.0001). We found no significant correlation between the concentration of IL1b, IL8, IL10, and IL2p70 with any epithelium parameters.
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.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
研究圆锥角膜患者和健康眼中炎症生物标志物与角膜上皮可量化指标之间的关系。
前瞻性观察性比较研究。
本研究纳入了100例患者的100只眼：48例圆锥角膜患者的48只眼和52例健康对照者的52只健康眼。
对两组患者的泪液细胞因子浓度进行研究：通过毛细管流动获取白细胞介素（IL）1B、IL6、IL8、IL10、IL12p70和肿瘤坏死因子α（TNFα），并使用流式细胞仪进行测量。从最靠近头皮的毛发段测定两组患者的皮质醇浓度，作为累积分泌的指标，并通过液相色谱质谱法进行测量。使用光学相干断层扫描（OCT）获取上皮变量。采用Pearson相关性（r）来测量两个不同变量之间的线性相关性。
研究炎症生物标志物（IL1B、IL6、IL8、IL10、IL12p70、TNFα和毛发皮质醇浓度）与OCT角膜上皮可量化变量之间是否存在相关性、相关性强度及意义，这些变量包括地形图的最小和最大上皮厚度、最小和最大厚度之差（上皮最小 - 最大厚度差）以及地形图上皮厚度的标准差（上皮标准差），以及地形图上下区域的平均上皮厚度。
与健康对照相比，圆锥角膜患者的眼睛中IL1b（P = 0.02）、IL6（P < 0.0001）、IL8（P < 0.0001）、TNFα（P < 0.0001）和毛发皮质醇浓度（P = 0.01）在统计学上显著更高。IL6与测量的上皮最小 - 最大厚度差[Pearson r = -0.59（-0.69，-0.47）；P < 0.0001]和上皮标准差（Pearson r = +0.56 [0.44，0.67]；P < 0.0001）之间存在显著相关性。毛发皮质醇浓度与上皮最小 - 最大厚度差（Pearson r = -0.27 [-0.42，-0.1]；P < 0.0001）和上皮标准差组（Pearson r = +0.2 [0.03，0.36]；P = 0.021）之间存在显著相关性。TNFα与上皮最大厚度之间也存在显著相关性（Pearson r = -0.37 [-0.55，0.17]；P < 0.0001）。我们发现IL1b、IL8、IL10和IL12p70的浓度与任何上皮参数之间均无显著相关性。
圆锥角膜患者眼中较高浓度的炎症标志物（IL6和毛发皮质醇）与识别上皮变异性的OCT指标（如上皮最小 - 最大厚度差和标准差）存在显著相关性。这些发现证明了慢性炎症在圆锥角膜患者眼中的作用，并且OCT检测到的这些上皮变化对这种炎症过程敏感。
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