IOBA (Institute of Applied OphthalmoBiology), University of Valladolid, Valladolid, Spain.
IOBA (Institute of Applied OphthalmoBiology), University of Valladolid, Valladolid, Spain; CIBER-BBN (Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine), Spain.
Ocul Surf. 2018 Jul;16(3):368-376. doi: 10.1016/j.jtos.2018.05.001. Epub 2018 May 14.
To evaluate the effect of 0.1%-fluorometholone (FML) on tear inflammatory molecule levels after 22-days treatment in dry eye disease (DED) patients exposed to an adverse controlled environment (ACE), identifying different biomarkers.
Analysis of a double-masked randomized clinical trial. Forty-one DED patients received 4-drops daily of topical FML (FML-group) or polyvinyl-alcohol (PA-group) for 22 days. At day 21, patients were exposed to an ACE. Tear samples were collected at V1 (baseline), V2 (pre-ACE), V3 (post-2-h-ACE) and V4 (24-h post-ACE). Concentrations of 18 molecules (EGF, IFN-γ, TNF-α, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8/CXCL8, IL-10, IL-12, IL-13, IL-17A, IP-10/CXCL10, MCP-1/CCL2, MIP-1α/CCL3, RANTES/CCL5 and MMP-9) were analyzed. Similarities among patients in molecule concentrations at V1 were evaluated. A linear-mixed effect model analyzed the influence of different variables on concentrations changes.
Multidimensional scaling (MDS) divided patients into two groups based on differences in EGF, IFN-γ, IL-8/CXCL8, RANTES/CCL5, and MMP-9 levels at V1. Groups had different clinical severities based on Schirmer test and conjunctival and corneal staining. IL-1RA, IL-2, and TNF-α were differentially affected by time, depending on treatment. Between V2-V3, there were significant changes in EGF, IL-1RA, IL-2, IL-8/CXCL8, IL-13, IP-10/CXCL10, TNF-α, and MMP-9. The strongest biomarker candidates were IFN-γ, RANTES/CCL5, and MMP-9 as DED severity biomarkers; IL-2 as DED therapeutic biomarker; and EGF as DED activity biomarker.
This clinical trial design using a controlled environment and the identified tear biomarkers could be useful to objectively select target patients, to define stress response, and to evaluate therapeutic endpoints in clinical trials.
评估 0.1%-氟米龙（FML）对暴露于不良控制环境（ACE）的干眼症（DED）患者在 22 天治疗后的泪液炎症分子水平的影响，确定不同的生物标志物。
这是一项双盲随机临床试验的分析。41 例 DED 患者接受每日 4 滴局部 FML（FML 组）或聚乙烯醇（PA 组）治疗 22 天。在第 21 天，患者暴露于 ACE。在 V1（基线）、V2（ACE 前）、V3（ACE 后 2 小时）和 V4（ACE 后 24 小时）采集泪液样本。分析了 18 种分子（EGF、IFN-γ、TNF-α、IL-1β、IL-1RA、IL-2、IL-4、IL-6、IL-8/CXCL8、IL-10、IL-12、IL-13、IL-17A、IP-10/CXCL10、MCP-1/CCL2、MIP-1α/CCL3、RANTES/CCL5 和 MMP-9）的浓度。评估了 V1 时患者在分子浓度上的相似性。线性混合效应模型分析了不同变量对浓度变化的影响。
多维尺度分析（MDS）根据 V1 时 EGF、IFN-γ、IL-8/CXCL8、RANTES/CCL5 和 MMP-9 水平的差异将患者分为两组。根据 Schirmer 测试和结膜及角膜染色，两组的临床严重程度不同。IL-1RA、IL-2 和 TNF-α受时间影响，取决于治疗。在 V2-V3 之间，EGF、IL-1RA、IL-2、IL-8/CXCL8、IL-13、IP-10/CXCL10、TNF-α和 MMP-9 均有显著变化。IFN-γ、RANTES/CCL5 和 MMP-9 是 DED 严重程度的最佳生物标志物候选物；IL-2 是 DED 的治疗生物标志物；EGF 是 DED 活性的生物标志物。
本临床试验设计使用控制环境和鉴定的泪液生物标志物可用于客观选择目标患者，定义应激反应，并评估临床试验中的治疗终点。
