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

Sheppard, John D.; Torkildsen, Gail; Geffin, Joel A.; Dao, Jung; Evans, David G.; Ousler, George W; Wilson, Jasmine; Baba, Stephanie N.; Senchyna, Michelle; Holland, Edward J.

doi:10.1016/j.jtos.2018.11.009

Cited by 30 publications

(43 citation statements)

References 29 publications

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“…This finding is likely explained by an afferent defect in the neural pathway of lacrimation possibly due to herpesvirus-induced corneal hypoesthesia, and is supported by corneal aesthesiometry data in our study population. This highlights the importance of assessing the nasolacrimal reflex for clinical and diagnostic purposes (3,17,31).…”

Section: Discussionmentioning

confidence: 99%

Altered Corneal Innervation and Ocular Surface Homeostasis in FHV-1-Exposed Cats: A Preliminary Study Suggesting Metaherpetic Disease

et al. 2021

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Metaherpetic disease is recognized in humans affected by herpes simplex virus-1 but is not reported in cats affected by feline herpesvirus-1 (FHV-1) despite the high prevalence of herpetic disease in this species and strong similarities in viral biology between alphaherpesviruses of humans and cats. This preliminary work evaluated cats naïve to FHV-1 (n = 9 cats, 18 eyes; control population) and cats naturally exposed to FHV-1 (n = 4 cats, 7 eyes), as confirmed by serologic testing and review of medical records. Antemortem assessment included clinical scoring, blink rate, corneal aesthesiometry, tear film breakup time (TFBUT), and Schirmer tear test-1 (STT-1) with or without the nasolacrimal reflex. Post-mortem assessment involved confocal microscopy of the corneas and evaluation of corneal nerves with ImageJ. Groups were compared with Student's t-tests and results are presented as mean ± standard deviation. Compared to control, herpetic cats had significantly higher (P ≤ 0.010) clinical scores (0.2 ± 0.4 vs. 4.6 ± 2.8) and response to nasolacrimal stimulation (7.8 ± 10.8% vs. 104.8 ± 151.1%), significantly lower (P < 0.001) corneal sensitivity (2.9 ± 0.6 cm vs. 1.4 ± 0.9 cm), STT-1 (20.8 ± 2.6 mm/min vs. 10.6 ± 6.0 mm/min), TFBUT (12.1 ± 2.0 s vs. 7.1 ± 2.9 s), and non-significantly lower blink rate (3.0 ± 1.5 blinks/min vs. 2.7 ± 0.5 blinks/min; P = 0.751). All parameters evaluated for corneal nerves (e.g., nerve fiber length, branching, occupancy) were notably but not significantly lower in herpetic vs. control cats (P ≥ 0.268). In sum, cats exposed to FHV-1 had signs suggestive of corneal hypoesthesia and quantitative/qualitative tear film deficiencies when compared to cats naïve to the virus. It is possible these are signs of metaherpetic disease as reported in other species.

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Section: Discussionmentioning

confidence: 99%

Altered Corneal Innervation and Ocular Surface Homeostasis in FHV-1-Exposed Cats: A Preliminary Study Suggesting Metaherpetic Disease

et al. 2021

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“…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.…”

Section: Discussionmentioning

confidence: 99%

Novel Extranasal Tear Stimulation: Pivotal Study Results

Moshfeghi

Periman

et al. 2020

Trans. Vis. Sci. Tech.

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“…The LFU is comprised of the lacrimal glands and the ocular surface, including the conjunctiva, cornea, and goblet cells, as well as the sensory and motor nerves that connect these structures to maintain tear production and quality. 7 The afferent pathway of this system includes the ophthalmic and maxillary branches of the trigeminal nerve, with abundant nerve fiber endings in the nasal mucosa. Normally, the trigeminal nerve is responsible for sensing pain and irritation in the nasal cavity and works to expel any foreign body or irritant that enters into the nasal cavity by prompting tear secretion.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 Previous clinical trials have demonstrated that the ITN is effective at stimulating tear production. 6,7,10 For example, Friedman et al found that stimulation with the ITN significantly increased Schirmer scores and decreased ocular staining and symptom scores from baseline. 10 In addition, Cohn et al found that the ITN was effective in inducing acute tear production after 90 days of use.…”

Section: Introductionmentioning

confidence: 99%

“…11 Sheppard et al also found that the ITN was effective in stimulating tear production with acute and long-term use. 7 There is also evidence that in addition to stimulating the lacrimal glands, the ITN may also stimulate the production of other components of the tear film including mucin and lipid. 12,13 While there is growing evidence that the ITN is effective at stimulating various components of the tear film, previous studies only included a few SS patients.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of an Intranasal Tear Neurostimulator in Sjögren Syndrome Patients

Lilley¹,

O’Neil²,

Bunya³

et al. 2021

OPTH

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Purpose: To assess the efficacy and safety of an intranasal tear neurostimulator (ITN) device in Sjögren syndrome (SS) patients. Methods: This was a two-visit prospective, randomized, controlled, same-day crossover study in participants with SS. Inclusion criteria were assessed at a baseline screening visit and included an Ocular Surface Disease Index (OSDI) score ≥13, and a Schirmer with anesthesia ≤10 mm/5 min (in at least one eye), with a cotton swab stimulation induced increase of ≥4 mm in the same eye. Participants returned for the application visit, where they received intranasal and extranasal applications of the ITN in random sequence, separated by at least 60 min. Schirmer scores were measured in both eyes after each application and compared to baseline values. Generalized linear models were performed to compare the change in Schirmer scores from baseline, and generalized estimating equations were used to account for correlations from repeated measurements in the same eye and measurements from two eyes of the same patient. Results: Fifty-five participants were screened and 35 were enrolled (all female), ranging in age from 31 to 72 years (mean, 57 years). The baseline OSDI score ranged from 14 to 91 (mean, 50.5), and the baseline Schirmer score had a mean (SD) of 6.4 (3.5) ranging from 0 to 20 (mm/5min). Improvement in Schirmer scores was significantly greater for intranasal device application (13.5 mm/5min, 95% CI: 10.4, 16.5) compared to extranasal device application (0.8mm/5min, 95% CI: −0.9, 2.4) (p<0.0001). The effects of the intranasal device application were significant regardless of the participant's baseline Schirmer score and systemic SS medication usage (p<0.05). Conclusion: Intranasal application of the ITN device significantly increased tear production in a subset of SS patients compared to baseline and was more effective than extranasal application. While production of the ITN device was recently discontinued, our findings suggest that other therapies that neurostimulate the lacrimal function unit may be effective in a subset of SS patients.

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

Cited by 30 publications

References 29 publications

Altered Corneal Innervation and Ocular Surface Homeostasis in FHV-1-Exposed Cats: A Preliminary Study Suggesting Metaherpetic Disease

Altered Corneal Innervation and Ocular Surface Homeostasis in FHV-1-Exposed Cats: A Preliminary Study Suggesting Metaherpetic Disease

Novel Extranasal Tear Stimulation: Pivotal Study Results

Efficacy of an Intranasal Tear Neurostimulator in Sjögren Syndrome Patients

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