Characterization of tear production in subjects with dry eye disease during intranasal tear neurostimulation: Results from two pivotal clinical trials.

Purpose: The intranasal tear neurostimulator (ITN) activates the nasolacrimal pathway, which is involved with basal and bolus tear secretion. These studies characterized the acute and long-term effectiveness of the ITN in stimulating tear production in subjects with dry eye disease (DED). Methods: Study 1: Randomized, double-masked, dual-controlled, 1-day crossover. Study 2: Single-arm, open label, 180-day prospective cohort. Eligible subjects had basal unstimulated Schirmer test (with anesthesia) <= 10 mm and intranasal cotton swab stimulated Schirmer test at least 7 mm greater in the same eye, and Ocular Surface Disease Index >= 13 and >= 23, in Studies 1 and 2, respectively. Study 1: Subjects (n = 48) received three randomized test applications: active intranasal, extranasal (active control), and sham intranasal (inactive control) stimulation, 3 min/application with 1-hour minimum between applications. Primary outcome measure was the difference in Schirmer test scores during active intranasal and control applications. Study 2: Subjects (n = 97) performed intranasal neurostimulation for <= 3 min/application, 2-10 times/day. Primary outcome measure was the difference in Schirmer scores (stimulated minus unstimulated) at day 180. Both studies recorded device-related adverse events (AEs). Results: Study 1: Schirmer scores (mean SEM) were significantly greater (p < 0.0001) with active intranasal (25.3 +/- 1.5 mm) vs extranasal (9.5 +/- 1.2 mm) and sham (9.2 +/- 1.1 mm) applications. Study 2: Schirmer scores were significantly greater (p < 0.0001) with ITN stimulation vs unstimulated at day 180 (17.3 +/- 1.3 mm vs 7.9 +/- 0.7 mm). No serious device-related AEs were reported in either study. Conclusion: The ITN was well-tolerated and effective in stimulating tear production with acute and long-term use in DED.