title: Randomized Controlled Crossover Trial Comparing the Impact of Sham or Intranasal Tear Neurostimulation on Conjunctival Goblet Cell Degranulation.
abstract: OBJECTIVE
  The aim of the study was to investigate the effects of the Allergan Intranasal Tear Neurostimulator (ITN) on conjunctival goblet cell (GC) degranulation.
  
  
  METHODS
  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 < .05). Moreover, although control subjects had a higher ratio of degranulated to nondegranulated GCs at baseline (0.75 ± 0.52) compared with the dry eye group (0.41 ± 0.27), the ratio became slightly higher in dry eye (2.04 ± 1.12 vs 1.99 ± 1.21 in control) after the ITN application. There was no significant difference between the IB or TB conjunctiva locations in terms of the effectiveness of the ITN application on conjunctival goblet cell secretory response.
  
  
  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.
authors.affiliation: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas; Erciyes University School of Medicine, Department of Ophthalmology, Kayseri, Turkey.
authors.forename: Koray
authors.initials: K
authors.lastname: Gumus
authors.affiliation: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.
authors.forename: Karri L
authors.initials: KL
authors.lastname: Schuetzle
authors.affiliation: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas. Electronic address: stevenp@bcm.edu.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D015550:Cell Degranulation / Q000187:drug effects*; D003228:Conjunctiva / Q000187:drug effects / Q000473:pathology*; D018592:Cross-Over Studies; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000628:therapy*; D005260:Female; D020397:Goblet Cells / Q000473:pathology*; D006801:Humans; D065346:Lubricant Eye Drops / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013666:Tears / Q000378:metabolism*; D041623:Tomography, Optical Coherence
chemical_list: D065346:Lubricant Eye Drops