Simulation of Acute Symptomatic Exacerbation in Dry Eye (DE) Patients After a Two Hour Exposure to Adverse Conditions in an Environmental Chamber

Abstract

Purpose: To simulate, in an environmental chamber, the acute exacerbation in symptoms and signs that Dry Eye (DE) patients often suffer when they are exposed to adverse conditions, usually consisting of low humidity and/or air flow.

Methods: Twenty mild-moderate DED patients (6 males, 14 females; 64.7 ± 1.8 years old) were subjected to a controlled adverse condition (5% relative humidity, 23°C temperature and localized air flow) for two hours in an environmental chamber (CERLab, IOBA, University of Valladolid, Spain). The following diagnostic tests were performed immediately before and after exposure: modified SIDEQ questionnaire, tear osmolarity, phenol red thread test, conjunctival hyperemia, fluorescein tear-breakup time (T-BUT), Schirmer’s test, corneal staining (Oxford and Baylor schemes), and conjunctival staining (Oxford scheme). Additionally, 16 molecules were analyzed in unstimulated tears (4 μl) by multiplex bead analysis in a Luminex IS-100: EGF, CX3CL1/fractalkine, IFN-γ, IL-10, IL-12p70, IL-17A, IL-1β, IL-1RA, IL-2, IL-6, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, TNF-α, VEGF, and MMP-9.

Results: After 2 hours in the controlled adverse condition, DE patients showed a significant (p<0.01) increase in corneal global staining (from 0.65 ± 0.15 to 1.10 ± 0.14) as well as in the nasal (p< 0.05), temporal (p<0.01) and inferior (p< 0.001) areas. Fluorescein T-BUT values significantly (p<0.001) decreased from 2.75 ± 0.53 to 1.90 ± 0.24. Interestingly, all patients complained about their eyes feeling remarkably worse after exiting the chamber but SIDEQ questionnaire failed to show that. Tear IL-6 levels significantly (p<0.05) increased from 38.6 ± 8.5 to 55.7 ± 9.7 pg/ml after exposure. Tear MMP-9 levels greatly increased, also significantly (p<0.01), from 894.8 ± 260.1 to 3829.0 ± 1202.3 pg/ml after the exposure.

Conclusions: Mild to moderate DE patients can be “acutely” inflamed in an environmental chamber resembling the sudden episodes of worsening that DE patients frequently suffer in their daily life. These exacerbations should be taken into account not only for the easiness of clinical trial recruitments and the reliability of the end points, but also for the design of therapeutics that can ameliorate these inflammatory episodes.

Keywords: 486 cornea: tears/tear film/dry eye • 490 cytokines/chemokines