Intranasal neurostimulation (TrueTear, Allergan) increases aqueous tear production in patients with moderate-to-severe aqueous deficiency dry eye disease (DED). In addition, the therapy maintains its benefit over 180 days of use, and continues to be safe and well-tolerated, according to results of an open-label study conducted to evaluate the long-term safety and effectiveness of the recently approved novel treatment.
Data collected in the study also demonstrated that the treatment improved corneal fluorescein staining (CFS) and symptoms, said Edward J. Holland, MD, professor of ophthalmology, University of Cincinnati, Cincinnati, OH.
“Certainly, the overall results of this research suggest that intranasal neurostimulation could be a potential treatment option to increase tear production in patients with moderate-to-severe DED,” Dr. Holland said. “We look forward to further clinical trials investigating this device.”
The treatment targets the nasolacrimal reflex by stimulating an ophthalmic branch of afferent trigeminal nerve fibers in the nasal cavity. It is a handheld device comprised of a reusable base unit that transmits small electrical pulses to a two-armed disposable tip that is inserted into the nasal cavities in contact with the anterior nasal mucosa.
Stimulation intensity can be adjusted using buttons on the device base, and the stimulation stimulation causes upregulation of parasympathetic activity in the superior salivatory nucleus of the brain.
“Intranasal neurostimulation with this device not only stimulates aqueous tear secretion from lacrimal glands, but recent studies show that the goblet cells and meibomian glands are also stimulated,” Dr. Holland said.
The long-term study screened 223 patients and enrolled 97 patients. Eligibility criteria required a baseline Schirmer score with anesthesia ≤10 mm/5min; CFS score ≥2 in at least one corneal region and a sum ≥4 for all regions in the same eye; Ocular Surface Disease Index (OSDI) ≥23; and no contact lens wear or history of chronic/recurrent epistaxis.
Entered patients had a mean CFS score in the study and fellow eye of 7.5 and a mean OSDI of 52.2.
Patients were instructed to use the neurostimulator at least twice a day and up to 10 times a day as needed, but for no more than 3 minutes per use.
“Analyses of device usage showed that patients used the device as was expected,” Dr. Holland said.
Mean number of device applications per subject over the entire study was 288 with an average of 1.7 uses per day for an average application time of 2.16 minutes. Eighty-nine of the 97 enrolled patients were evaluated at day 180.
The study met its primary effectiveness endpoint that assessed difference in Schirmer test score during stimulation compared with before stimulation at day 180 in the study eye. Acute tear production was also significantly increased in the fellow eye at day 180 and in both the study and fellow eyes when assessed at all earlier study visits (days 0, 7, 30, 90).
CFS score was significantly improved in the study eye for the total score and inferior region at day 7 and in the fellow eye for the central and temporal regions at day 7 and for the total score and central region at day 30.
At days 7 and 30, statistically significant improvements from baseline were observed for all items in a dry eye symptom questionnaire and in the total OSDI score. In a satisfaction survey, almost two-thirds of patients reported that their dry eye symptoms were better or somewhat better at day 180.
Discussing safety, Dr. Holland said that when the concept was originally proposed, there were concerns about the potential for serious adverse events. No serious device-related events were reported in the study, however.
Overall, there were 36 device-related adverse events reported by 30 patients. Nearly all were self-limited, and none led to permanent sequelae. The only device-related adverse events occurring at a rate >5% were nasal pain, discomfort or burning (10.3%); nosebleed (5.2%); and transient electrical discomfort (5.2%).
Dr. Holland is a consultant to Allergan.