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

Abstract

Purpose The aim of the study was to investigate the effects of the Oculeve Intranasal Lacrimal Neurostimulator (ILN) on conjunctival goblet cell 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 three-visit study consisting of one screening and two separate randomized-masked ILN treatments (sham extranasal or intranasal). Tear meniscus height (TMH) was measured by AS-OCT before and after applications. Impression cytology (IC) was taken from the bulbar conjunctiva of the right eye for PAS staining and from the left eye for MUC5AC mucin immunostaining at baseline and after each treatment. The ratio of degranulated to non-degranulated GCs was measured as a marker of secretion. Results In all participants, both IB and TB cytology specimens stained for MUC5AC revealed a significantly higher ratio of degranulated to non-degranulated GCs after the ILN (IB: 2.28 ± 1.27 and TB: 1.81 ± 1.01) compared to baseline (IB: 0.56 ± 0.55, p= 0.015) (TB: 0.56 ± 0.32, p= 0.003) and extranasal sham application (IB: 0.37 ± 0.29, p= 0.001) (TB: 0.39 ± 0.33, p= 0.001). When the same analysis was repeated in the dry eye or control groups, the ratio was significantly higher after ILN than the baseline ratio and ratio after extranasal application in both groups (p< 0.05). Moreover, while control subjects had higher ratio of degranulated to non-degranulated GCs at baseline (0.75 ± 0.52) compared to 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 ILN application. There was no significant difference between the IB or TB conjunctiva locations in terms of the effectiveness of the ILN application on conjunctival goblet cell secretory response. Conclusions These preliminary results document that the Oculeve ILN can stimulate degranulation of goblet cells in the conjunctiva, which is a promising new approach for the management of dry eye. This study protocol was registered on ClinicalTrials.gov (#NCT02385292)

Novel Extranasal Tear Stimulation: Pivotal Study Results

“…Further studies of the TrueTear device confirmed its efficacy for the treatment of DED using additional parameters, including tear meniscus height, degranulation of conjunctival goblet cells, and their area. [19][20][21][22][23][24][25][26][27] The effects of the ITN device on corneal staining as well as the protein and lipid component of tears differ across various studies, 8,20,22,[24][25][26][27] warranting further investigation. Despite its efficacy and safety for the treatment of DED, the ITN device requires deep insertion into the nose, which makes it not practical or comfortable for many patients.…”

BCLA CLEAR – Contact lens technologies of the future

“…An alternative approach to the treatment of DED focuses on increasing tear production by incorporation of an electrical stimulator into a contact lens. This concept is based on a similar intranasal stimulator technology (TrueTear, Allergan, CA, USA) which delivers an intranasal electrical stimulus to stimulate tearing [151] and promote goblet cell secretion [152]. A recent patent highlighted the potential for this type of technology to be manufactured in the form of a contact lens [153].…”

Review of Biomarkers in Ocular Matrices: Challenges and Opportunities

“…Gumus et al . investigated the effects of the Allergan Intranasal Tear Neurostimulator (ITN) on conjunctival goblet cell function in a 15-participant (5 normal and 10 dry eyes), study ( 134 ). IC samples were taken at baseline and after each treatment: right eye samples were used for PAS staining and left eye samples were used for MUC5AC mucin immunostaining.…”