A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease

Abstract

Background: Dry eye disease (DED), a chronic disorder affecting the tear film and lacrimal functional unit, is a widely prevalent condition associated with significant burden and unmet treatment needs. Since specific neural circuits play an important role in maintaining ocular surface health, microelectrical stimulation of these pathways could present a promising new approach to treating DED. This study evaluated the efficacy and safety of nasal electrical stimulation in patients with DED.

Methods: This prospective, open-label, single-arm, nonrandomized pilot study included 40 patients with mild to severe DED. After undergoing two screening visits, enrolled subjects were provided with a nasal stimulation device and instructed to use it at home four times daily (or more often as needed). Follow-up assessments were conducted up to day 180. The primary efficacy endpoint was the difference between unstimulated and stimulated tear production quantified by Schirmer scores. Additional efficacy endpoints included change from baseline in corneal and conjunctival staining, symptoms evaluated on a Visual Analog Scale, and Ocular Surface Disease Index scores. Safety parameters included adverse event (AE) rates, visual acuity, intraocular pressure, slit-lamp biomicroscopy, indirect ophthalmoscopy, and endoscopic nasal examinations.

Results: Mean stimulated Schirmer scores were significantly higher than the unstimulated scores at all visits, and corneal and conjunctival staining and symptom scores from baseline to day 180 were significantly reduced. No serious device-related AEs and nine nonserious AEs (three device-related) were reported. Intraocular pressure remained stable and most subjects showed little or no change in visual acuity at days 30 and 180. No significant findings from other clinical examinations were noted.

Conclusion: Neurostimulation of the nasolacrimal pathway is a safe and effective means of increasing tear production and reducing symptoms of dry eye in patients with DED.

Keywords: keratoconjunctivitis sicca; nasolacrimal reflex; neuromodulation; neurostimulation; ocular staining; tear production.

Figure 1

Schirmer scores with and without stimulation. Notes: The difference between the stimulated and unstimulated Schirmer score for each eye was statistically significant at all time points (P<0.001). Data represents mean ± SEM. The thin dashed horizontal reference line represents the mean unstimulated value for both eyes at day 0. Abbreviations: OD, right eye; OS, left eye; SEM, standard error of the mean.

Figure 2

Corneal staining. Notes: Corneal staining scores were numerically reduced from baseline in both eyes at all time points after day 7. Bars represent SEM. The thin dashed horizontal reference line represents the baseline value at day 0. Abbreviations: OD, right eye; OS, left eye; SEM, standard error of the mean.

Figure 3

Conjunctival staining. Notes: Conjunctival staining scores were significantly reduced from baseline in both eyes at all time points after day 30 (P<0.05). At day 180, the mean changes from baseline ranged from −1.8±0.5 to −2.2±0.51 (P=0.002). Bars represent SEM. The thin dashed horizontal reference line represents the baseline value at day 0. Abbreviations: OD, right eye; OS, left eye; SEM, standard error of the mean.

Figure 4

DED symptoms (VAS score). Notes: Patients used the eight-item DES VAS to rate symptoms due to ocular dryness, where 0% = no discomfort and 100% = maximal discomfort. At each study visit (days 7, 14, 30, 60, 90, and 180), the mean changes from baseline for each of the eight VAS categories were statistically significant (P<0.001). The thin dashed horizontal reference line represents the baseline value at day 0. Abbreviations: DED, dry eye disease; DES, dry eye symptom; FBS, foreign body sensation; VAS, Visual Analog Scale.

Figure 5

DED severity (OSDI score). Notes: Mean changes in OSDI scores from baseline were statistically significant (P<0.001) at all time points after the baseline (day 0) visit. The thin dashed horizontal reference line represents the baseline value at day 0 (OSDI raw score at day 0=69.3±2.6). Bars represent SEM. Abbreviations: DED, dry eye disease; OSDI, Ocular Surface Disease Index; SEM, standard error of the mean.

Figure 6

Schirmer scores at day 180 according to DEWS severity categories. Notes: Nasal stimulation led to a statistically significant increase in Schirmer scores, as compared with unstimulated values, in both patients with DEWS severity levels I–II and those with severity levels III–IV. *Indicates statistically significant difference (P<0.001) between stimulated and unstimulated Schirmer score. Bars represent SEM. Abbreviations: DEWS, Dry Eye Workshop; OD, right eye; OS, left eye; SEM, standard error of the mean.