RT info:eu-repo/semantics/article T1 Response profiles to a controlled adverse desiccating environment based on clinical and tear molecule changes A1 Fernández Martínez, Itziar A1 López Miguel, Alberto A1 Enriquez De Salamanca Aladro, Amalia A1 Tesón Yudego, María Luisa A1 Stern, Michael A1 González García, María Jesús A1 Calonge, Margarita AB Purpose:To investigate response profiles in the lacrimal functional unit of dry eye disease (DED) and healthy volunteers after exposure to a controlled adverse desiccating environment (CADE) by identifying groups of individuals with similar clinical and molecular changes.Methods:Clinical parameters and tear molecule levels of 20 mild-moderate DED patients and 20 healthy volunteers were evaluated pre- (baseline) and post-CADE exposure. Clustering based on relative change from baseline values was used to identify response profiles. One-vs-all logistic regression was used to identify baseline predictors for response clusters.Results: Four response profiles were identified. Cluster 1: tear break-up time (TBUT) decrease and matrix metalloproteinase 9 (MMP-9) increase. Cluster 2: marked increase in corneal staining, up-regulation of both MMP-9 and interleukin (IL)-6 levels, and down-regulation of epithelial growth factor (EGF). Cluster 3: increase in fractalkine, vascular endothelial growth factor (VEGF), MMP-9, IL-6, IL-8, IL-1 receptor antagonist (IL-1Ra) and RANTES (regulated on activation, normal T expressed and secreted) tear levels; and increased corneal staining and decreased TBUT and phenol red thread scores. Cluster 4: decreased single-item score dry eye questionnaire (SIDEQ) scores and increased corneal staining. Predictive models using baseline variables found that cluster membership depended on: corneal and conjunctival staining, SIDEQ score, interferon gamma-induced protein (IP)-10, VEGF, and IL-1Ra concentrations.Conclusions:The response of both mild-moderate DED and healthy asymptomatic individuals to environmental stress (CADE) can be predicted based on baseline (pre-exposure) clinical and tear molecular parameters. Thus, identifying individuals with a predictable response could improve patient enrollment in DED clinical trials. PB Elsevier YR 2019 FD 2019 LK http://uvadoc.uva.es/handle/10324/45253 UL http://uvadoc.uva.es/handle/10324/45253 LA eng NO Ocul Surf, 2019 Jul;17(3):502-515. NO Producción Científica DS UVaDOC RD 28-nov-2024