Randomized Controlled Crossover Trial Comparing the Impact of Sham or Intranasal Tear Neurostimulation on Conjunctival Goblet Cell Degranulation

Purpose The aim of the study was to investigate the effects of the Allergan Intranasal Tear Neurostimulator (ITN) on conjunctival goblet cell (GC) degranulation. Design A randomized, double-masked, placebo-controlled crossover trial. Methods A total of 15 subjects (5 normal and 10 dry eye) were enrolled in a 3-visit study consisting of 1 screening and 2 separate randomized-masked ITN treatments (sham extranasal or intranasal). Tear meniscus height (TMH) was measured by anterior segment optical coherence tomography before and after applications. Impression cytology (IC) was taken from the bulbar conjunctiva of the right eye for periodic acid–Schiff staining and from the left eye for MUC5AC mucin immunostaining at baseline and after each treatment. The ratio of degranulated to nondegranulated GCs was measured as a marker of secretion. Results In all participants, both inferior bulbar (IB) and temporal bulbar (TB) cytology specimens stained for MUC5AC revealed a significantly higher ratio of degranulated to nondegranulated GCs after the ITN (IB: 2.28 ± 1.27 and TB: 1.81 ± 1.01) compared to baseline (IB: 0.56 ± 0.55, P  = .015) (TB: 0.56 ± 0.32, P  = .003) and extranasal sham application (IB: 0.37 ± 0.29, P  = .001) (TB: 0.39 ± 0.33, P  = .001). When the same analysis was repeated in the dry eye or control groups, the ratio was significantly higher after ITN than the baseline ratio and ratio after extranasal application in both groups ( P Conclusions These preliminary results document that the Allergan ITN can stimulate degranulation of goblet cells in the conjunctiva, which is a promising new approach for the management of dry eye.