Neural stimulation for dry eye enters FDA clinical trial phase.


In the United States alone, moderate and severe dry eye disease afflicts nearly 5 million individuals over age 65, and many more suffer from less-severe cases. Dry eye symptoms range from mild itchy irritation to severe eye pain and occurs when the eye does not produce tears properly, or when tears are not of the correct consistency and evaporate too quickly.  In addition, inflammation of the surface of the eye may occur along with dry eye. If left untreated, this condition can lead to pain, ulcers, or scars on the cornea, and some loss of vision.  Currently it does not have an effective treatment.  Now, researchers from Stanford University state that they have developed a device that electronically stimulates tear production, which will offer hope to sufferers of dry eye syndrome, one of the most common eye diseases in the world.  The opensource study is published in the Journal of Neural Engineering.

Previous studies show that treatments to increase tear volume at the eye surface, which include anti-inflammatory drugs, artificial ointments, surgery or eye drops, provide only short-term relief or are plagued with side effects.  Early electrophysiological studies, aimed at identifying the nerves responsible for lacrimation, discovered enhanced tear secretion upon electrical stimulation of the efferent facial nerve, superior cervical ganglion neurons, and afferent branches of the trigeminal nerve. Acinar cell voltage–gated ion channels play a key role in tear secretion and are also electrically excitable. Earlier studies from the team introduced electrical stimulation of the lacrimal nerve and gland to increase tear volume and treat dry eye disease.  The current study reveals the stimulation pathways and identifies electrical parameters for maximum tear secretion to determine acute tissue damage thresholds using a chronically implanted stimulator.

The current study used a device, 16 mm long, 3-4 mm wide and 1-2 mm thick, implanted beneath the inferior lacrimal gland in rabbit eyes. Results show that when it is activated wirelessly, it increases the generation of tears by nearly 57%.  Data findings show that the afferent neural pathway, the neural pathway from sensory neurons to the brain which activates the reflex tearing, offered an even more efficient way to enhance tear production.

To determine the neural pathways involved in enhanced tear secretion during lacrimal gland stimulation, the lab delivered scopolamine, prazosin and hexamethonium.  Results show that scopolamine blocked the response to gland stimulation, which indicates that the parasympathetic pathway facilitated the tear response, not the sympathetic pathway. Data findings show that gland stimulation did not produce reflex tearing, as evidenced by the lack of change in the tear volume after the reflex pathway was inhibited with hexamethonium. The group note that reflex response to nerve stimulation of the cornea and ethmoid nerve was completely blocked by the application of hexamethonium.

Results show that electrical stimulation of the lacrimal gland engages primarily the efferent cholinergic pathway to enhance tear secretion and although isofluorane anesthesia should not affect efferent stimulation, it could inhibit a reflex tear response originating from the sensory portion of the lacrimal nerve within the gland. Data findings show that stimulating the afferent ethmoid nerve pathway increased tearing nearly as much as gland stimulation using less current and pulse duration. Therefore, the team conclude that ethmoid nerve stimulation or another sensory branch of the ophthalmic nerve may be more productive for eliciting tearing, and future experiments will attempt afferent nerve stimulation without general anesthesia.

The team surmise that electrical stimulation of the lacrimal gland can safely and significantly increase tear secretion, and this effect is mediated by efferent parasympathetic nerves. They go on to add that stimulation of the afferent nerves also enhances tear production, and both targets could be explored in clinical tests. For the future, the researchers state that the next phase of the research will be to evaluate the ‘quality’ of the tears produced, as in addition to volume, protein and lipid content are important. They go on to conclude that the device is currently undertaking clinical trials for FDA approval.

Source: Stanford Biodesign

Chronic stimulator and placement. (a) Fully-implantable stimulator with a 3 mm diameter active electrode. (b) Wireless power transmitter with pulse duration control. (c) Stimulator within the orbit, adjacent to the inferior lacrimal gland. Electronic enhancement of tear secretion. Palankar et al 2015.

Chronic stimulator and placement. (a) Fully-implantable stimulator with a 3 mm diameter active electrode. (b) Wireless power transmitter with pulse duration control. (c) Stimulator within the orbit, adjacent to the inferior lacrimal gland. Electronic enhancement of tear secretion. Palankar et al 2015.

 

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