New tools in dry eye disease research: a more efficient clinical trial design using controled environment and molecular biomarkers, and a new clinical questionnaire

Abstract

The main aims of this doctoral thesis were 3: 1) to study the usefulness of a new two-step design of clinical trials using a controlled environment chamber to evaluate the safety and efficacy of new dry eye disease (DED) therapies; 2) to evaluate the effect of a common DED therapy on clinical symptoms and signs and tear inflammatory molecule levels at different time points (i.e. pre- and post-treatment, pre- and post-adverse environmental condition [ACE; 23°C temperature, 5% relative humidity, 0.43 m/s localized airflow] exposure), identifying different biomarkers (disease severity, therapeutic efficacy, and disease activity); 3) to analyze why clinical symptoms usually fail at translating what patients feel and to develop a new and simpler questionnaire that can detect changes in DED-related symptoms between two time-points in an easier and yet more accurate way than the current questionnaires. Methodology: To meet the first and second aims, a single-center, double masked, randomized, vehicle-controlled, phase II clinical trial was conducted, assessing the efficacy of topical 0.1%-fluorometholone in moderate-to-severe DED patients for ameliorating the worsening of the ocular surface when exposed to an adverse environment. A total of 41 patients randomly received one drop 4 times daily of either topical 0.1%-fluorometholone (FML group) or polyvinyl alcohol (PA group) for 22 days. During the 4 visits of the study (V1, day 0, baseline / V2; day 21, pre-ACE exposure / V3, day 21, post-ACE exposure / V4, day 22, 24h post-ACE exposure) DED signs and symptoms were evaluated. Also, tear samples were collected at the beginning of each visit for further analysis. An immune bead-based array analyzed the 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, IP10/CXCL10, MCP-1/CCL2, MIP-1α/CCL3, RANTES/CCL5 and MMP-9).