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

Abstract

PURPOSE\nThe 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).\n\n\nMETHODS\nStudy 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\u202fmm and intranasal cotton swab-stimulated Schirmer test at least 7\u202fmm greater in the same eye, and Ocular Surface Disease Index® ≥13 and\u202f≥\u202f23, in Studies 1 and 2, respectively. Study 1: Subjects (n\u202f=\u202f48) received three randomized test applications: active intranasal, extranasal (active control), and sham intranasal (inactive control) stimulation, 3\u202fmin/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\u202f=\u202f97) performed intranasal neurostimulation for ≤3\u202fmin/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).\n\n\nRESULTS\nStudy 1: Schirmer scores (mean\u202f±\u202fSEM) were significantly greater (p\u202f<\u202f0.0001) with active intranasal (25.3\u202f±\u202f1.5\u202fmm) vs extranasal (9.5\u202f±\u202f1.2\u202fmm) and sham (9.2\u202f±\u202f1.1\u202fmm) applications. Study 2: Schirmer scores were significantly greater (p\u202f<\u202f0.0001) with ITN stimulation vs unstimulated at day 180 (17.3\u202f±\u202f1.3\u202fmm vs 7.9\u202f±\u202f0.7\u202fmm). No serious device-related AEs were reported in either study.\n\n\nCONCLUSION\nThe ITN was well-tolerated and effective in stimulating tear production with acute and long-term use in DED. CLINICALTRIALS.\n\n\nGOV IDENTIFIER\nNCT02680158 and NCT02526290.