Journal
OCULAR SURFACE
Volume 17, Issue 3, Pages 502-515Publisher
ELSEVIER
DOI: 10.1016/j.jtos.2019.03.009
Keywords
Dry eye disease; Controlled adverse desiccating environment; Clustering; Predictors; Clinical signs; Tear molecules
Categories
Funding
- Instituto de Salud Carlos III (Ministerio de Ciencia, Innovacion y Universidades, Spain), through research project RETICS [RD16/008/0001]
- Instituto de Salud Carlos III (Ministerio de Ciencia, Innovacion y Universidades, Spain), through research project Centro de Investigacion Biomedica en Red de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN) [CB06/01/003]
- Agencia Estatal de Investigacion (AEI) [SAF2016-77080-P]
- Fondo Europeo de Desarrollo Regional (FEDER), UE
- Ministerio de Ciencia, Innovacion y Universidades (Spain)
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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.
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