Neurostimulation of the Lacrimal Nerve for Enhanced Tear Production

Kossler, Andrea L; Wang, Jianhua; Feuer, William J.; Tse, David T.

doi:10.1097/iop.0000000000000234

Cited by 22 publications

(23 citation statements)

References 43 publications

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“…28 Furthermore, histopathologic examination of the lacrimal glands showed no tissue damage from chronic neurostimulation. 28 In another study, Brinton and his colleagues implanted bipolar platinum foil electrodes beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve of rabbits. 30 A 4.5 mm (125%) increase in the Schirmer test was noted after lacrimal gland stimulation with 3mA, 500 μs pulses at 70 Hz.…”

Section: Discussionmentioning

confidence: 92%

“…28 The UHR-OCT revealed a 441% average increase in tear production after LNS. 28 Furthermore, histopathologic examination of the lacrimal glands showed no tissue damage from chronic neurostimulation. 28 In another study, Brinton and his colleagues implanted bipolar platinum foil electrodes beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve of rabbits.…”

Section: Discussionmentioning

confidence: 94%

“…24 Previous studies have demonstrated that the lacrimal gland secretes in response to cholinergic (acetylcholine, vasoactive intestinal peptide - VIP) and α-and β-adrenergic neurotransmitters. 25–27 Tear secretion can also be induced by electrical stimulation of the afferent and efferent nerves proximal to the lacrimal gland 28, 29 One study that investigated the response pathways and electrical parameters to maximize tear secretion have documented that electrical stimulation of the lacrimal gland engages primarily the efferent cholinergic pathway to enhance tear secretion. 30 …”

Section: Discussionmentioning

confidence: 99%

“…28, 30 In one study, Kossler and his colleagues implanted a neurostimulator adjacent to the right lacrimal nerve. 28 After 2 minutes of lacrimal nerve stimulation (LNS) (100 μs, 1.6 mA, 20 Hz, 5–8V), the authors measured tear volume using ultra high-resolution optical coherence tomography (UHR-OCT). 28 The UHR-OCT revealed a 441% average increase in tear production after LNS.…”

Section: Discussionmentioning

confidence: 99%

“…28 After 2 minutes of lacrimal nerve stimulation (LNS) (100 μs, 1.6 mA, 20 Hz, 5–8V), the authors measured tear volume using ultra high-resolution optical coherence tomography (UHR-OCT). 28 The UHR-OCT revealed a 441% average increase in tear production after LNS. 28 Furthermore, histopathologic examination of the lacrimal glands showed no tissue damage from chronic neurostimulation.…”

Section: Discussionmentioning

confidence: 99%

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

Gümüş

Schuetzle

Pflugfelder

2017

American Journal of Ophthalmology

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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)

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Section: Discussionmentioning

confidence: 92%