Response profiles to a controlled adverse desiccating environment based on clinical and tear molecule changes

Area of Science:

• Ophthalmology
• Immunology
• Molecular Biology

Background:

• Dry eye disease (DED) affects the lacrimal functional unit, leading to discomfort and visual impairment.
• Understanding individual responses to environmental stressors is crucial for managing DED.
• Controlled adverse desiccating environment (CADE) exposure simulates real-world conditions to study ocular surface stress.

Purpose of the Study:

• To identify distinct response profiles within the lacrimal functional unit of DED patients and healthy volunteers.
• To characterize clinical and molecular changes following exposure to a controlled adverse desiccating environment (CADE).
• To identify baseline predictors for these response profiles.

Main Methods:

• Evaluated clinical parameters and tear molecule levels in 20 mild-moderate DED patients and 20 healthy volunteers.
• Utilized clustering based on relative changes from baseline after CADE exposure to define response profiles.
• Employed logistic regression to identify baseline predictors for cluster membership.

Main Results:

• Four distinct response profiles were identified based on changes in tear break-up time (TBUT), corneal staining, and specific tear cytokines (MMP-9, IL-6, EGF, fractalkine, VEGF, IL-8, IL-1Ra, RANTES).
• One profile showed decreased TBUT and increased MMP-9; another exhibited increased corneal staining, MMP-9, IL-6, and decreased EGF.
• A third profile presented elevated levels of multiple inflammatory markers and reduced TBUT/phenol red thread scores, while the fourth showed decreased dry eye questionnaire scores and increased corneal staining.
• Baseline predictors for cluster membership included corneal/conjunctival staining, SIDEQ scores, IP-10, VEGF, and IL-1Ra concentrations.

Conclusions:

• Individual responses to environmental stress in both DED patients and healthy individuals can be predicted using baseline clinical and molecular data.
• Identifying predictable response patterns can optimize patient selection for DED clinical trials.
• This approach offers a pathway to more targeted and efficient research in dry eye disease.