By Liz Hillman
Intranasal device stimulates a reflex pathway that produces natural tears for dry eye patients
From warm compresses to drops to punctal plugs, there are a range of options to offer some relief to dry eye patients. Yet a 2008 survey of nearly 8,000 ophthalmologists in the U.S. revealed that 94% felt more treatment options were needed for patients with a moderate to severe form of the disease.
Michael Ackermann, PhD, vice president of neurostimulation, Allergan, San Francisco, held a biodesign fellowship at Stanford University from 2010 to 2012. There he spent a month in the ophthalmology department, observing clinical care and looking for opportunities where it could be improved. Dry eye quickly presented itself as an obvious problem. It seemed like every third patient was coming in the door with dry eye, he said. Doing a deep dive into the pathophysiology of this disease, Dr. Ackermann and his colleagues gained an understanding of the neural pathways involved in tear production. This led them to create a device that could stimulate natural tear production using electrical stimulation, a technique common in other areas of medicine such as pain control and movement disorder treatment. Neurostimulation in general is a very widely used type of technology. Whats so neat about it is it offers clinicians the opportunity to allow patients to treat themselves by activating their own tear production system, Dr. Ackermann said. It turns out that the tear film is made of up 3 components, all of which are neurally innervated. Dr. Ackermann started the company Oculeve, which was acquired by Allergan (Dublin) in July 2015, to further develop the device, which began as a surgical implant less than the size of a fingertip. In its current design iteration though, the Oculeve Intranasal Tear Neurostimulator is a nonsurgical, externally applied device. It consists of a rechargeable handheld unit and a disposable hydrogel tip, which is inserted into the nasal passage and used to stimulate the trigeminal nerve. Three studies using the neurostimulator were presented at the 2016 ASCRS•ASOA Symposium & Congress in New Orleans: 1 randomized and controlled trial showing increased tear production over 2 controls (Richard Lewis, MD); 1 study showing safety and effectiveness over 180 days of use (Arturo Chayet, MD); and 1 randomized and controlled study showing that the device increases the mucin layer and the aqueous layer of the tear film with stimulation (Stephen Pflugfelder, MD).
Oculeve was not originally destined to be an externally applied device, but a chance observation in some patients with the implant led to this discovery. We realized that some of the patients, even though they had a unilateral implant on in 1 orbit, were actually getting bilateral tearing. It became pretty obvious that our best responding patients were getting an activation through an afferent reflex of the tearing process, Dr. Ackermann said. While having lunch with a colleague, Jim Loudin, PhD, and discussing other reflex pathways that could be used to stimulate this tear production, the possibility of using the nasal pathway came up. The next thing we knew, we were finishing up lunch pretty quickly and were getting back to start that process, Dr. Ackermann said, adding later that the nasal pathways effect on tear production was known before, but no one had thought to tap it for dry eye treatment. A study published earlier this year in the Journal of Neural Engineering described the actual pathway stimulated by the system. This study was conducted to evaluate the earlier implant version of the device and use of the the nasal reflex device in rabbit subjects. It found that while electrical stimulation of the lacrimal gland was effective at producing tears, stimulation of the afferent ethmoid nerve (nasal) pathway was more effective.2 Whats more, this latter stimulation activated other glands that secreted lipids and proteins, creating a more satisfying and natural dry eye treatment. It turns out this activation was much more potent, said 1 of the study authors Daniel Palanker, PhD, professor, Department of Ophthalmology and Hansen Experimental Physics Laboratory, Stanford University, Stanford, California. Its a more natural kind of tears that are secreted. Dr. Palanker said dry eye patients with electro-neural stimulated tears had improved symptomatology and corneal staining in clinical trials, which he said indicates that their disease was reverting. Dr. Ackermann said Allergan hopes to submit the Oculeve Intranasal Tear Neurostimulator to the U.S. Food and Drug Administration for approval this summer. Were very optimistic about the device, he said. [Weve had a] very positive response from patients and clinicians, and I think the future is bright.
1. Asbell PA, et al. Ophthalmologist perceptions regarding treatment of moderate-to-severe dry eye: results of a physician survey. Eye Contact Lens. 2010;36:338.
2. Brinton M, et al. Electronic enhancement of tear secretion. J Neural Eng. 2016;13:016006.