In the third episode of Dry Eye Fireside Chat, Damon Dierker, OD, FAAO, speaks with Hardeep Kataria, OD, FAAO, and Ahmad Fahmy, OD, FAAO, Dipl. ABO, about the relationship between the lacrimal functional unit (LFU) and neurostimulation.
The clinicians discuss how neurostimulation offers an alternative pathway to treating dry eye disease (DED) in patients, particularly in those with poor treatment responses from other pharmaceutical interventions.
Key physiological characteristics of DED: tear film instability and inflammation
To start, Dr. Dierker highlighted the evolving understanding of the pathogenesis of DED and how that impacts treatment and management approaches. When diagnosing dry eye patients, Dr. Fahmy expressed that, in his medical opinion, tear film instability is one of the most reproducible signs of dryness, making it a useful indicator while evaluating patients.
Additionally, tear film instability is a common factor across various types of dry eye, including evaporative, aqueous deficient, and neurogenic, or a combination thereof. Further, now that it is better understood that dry eye can have a multitude of causes, Dr. Kataria explained that combining this knowledge with the fundamentals of how the tear film functions—namely in delivering nutrients to the ocular surface/structures—can be crucial to treating dryness.
It is also important to keep in mind that the tear film is exposed to different particulate matter in the air from distinct environments (i.e., industrial pollution, dust, smoke, allergens, etc.), which can induce a dry eye flare-up, added Dr. Fahmy. As a major feature of ocular surface disease (OSD), inflammation is another characteristic that is helpful for clinicians to target during diagnostic testing and evaluations.
Dr. Kataria mentioned that DED almost always has an inflammatory component, but other factors, such as hyperosmolarity of the tear film and neurosensory abnormalities, are also important to consider when treating a patient. Research into the neurogenic pathogenesis of dry eye continues to uncover many exciting approaches to effectively treating DED.
What is the lacrimal functional unit?
Dr. Kataria explained that the lacrimal functional unit is a self-regulating system made up of the corneal and conjunctival epithelium, lacrimal gland, accessory lacrimal glands, meibomian glands, and goblet cells.
In addition, she highlighted that it’s important not to forget that the LFU does include all of the innervation involved in maintaining those structures, allowing it to respond to stimuli and be responsible for tear production, clearance, and distribution on the ocular surface.
Neurostimulation’s unique mechanism of action to treat DED
Disruption of the neural feedback loop leads to downstream effects such as corneal epithelial changes, remarked Dr. Fahmy. As such, the LFU provides clinicians with a reminder to treat DED with a comprehensive understanding of the different causes of epitheliopathy. While many patients may present with similar symptoms, the underlying cause can be unique to every individual, which is why it’s crucial to understand that the LFU is a complex system with many moving parts.
When talking about the nasolacrimal reflex, mentioning the accessory pathway of tear production is essential, highlighted Dr. Kataria. She explained that chronic inflammation in the trigeminal parasympathetic pathway impacts the innervation surrounding the LFU, sending a signal to the brain to stimulate the efferent secretomotor nerve fibers synapsing at the lacrimal gland amongst other ocular surface structures.
But what if there is a breakdown within one of the structures of the LFU, she asked, how can clinicians continue to access this pathway? She answered that there is a branch of the nasociliary nerve, called the anterior ethmoidal nerve, where clinicians can still access the tearing reflex through a parallel process. This mechanism is thought to be how neurostimulation can be used to treat dry eye.
How to implement neurostimulation into clinical practice
While initially device-driven, neurostimulation has shifted recently to feature a pharmacological agent, such as Tyrvaya (varenicline solution nasal spray 0.03mg, Viatris), which was approved by the Food and Drug Administration (FDA) in October 2021. Dr. Fahmy noted that while electrical stimulation differs from pharmacological stimulation, they function similarly to increase basal tear secretion, meaning that all three layers of the tear film are being reintroduced to the ocular surface, not simply reflexive tearing.
Dr. Fahmy added that in his practice, many of his patients have dry eye with components from both aqueous deficient and evaporative dry eye. As such, neurostimulation-based treatments could be considered in his professional medical opinion as one of the fundamental therapies that he recommends to dry eye patients because they can work so broadly and effectively.
Dr. Kataria highlighted that her approach to implementing neurostimulation interventions into clinical practice is slightly different, as she finds it to be helpful as an adjunctive therapy. Due to the fact that she treats many glaucoma patients and those with multiple co-morbid conditions, such as meibomian gland dysfunction, ocular rosacea, blepharitis, etc., she often starts patients on immunomodulators to target specific inflammatory mediators to prevent disease progression.
Then, she considers prescribing a neurostimulatory therapy like Tyrvaya as an adjunctive therapy to reduce the medication burden for glaucoma patients while still stimulating endogenous tear production.
Patient selection for neurostimulatory interventions
Dr. Fahmy mentioned that even for patients with hyper-evaporative dry eye and a slightly low tear meniscus, he recommends neurostimulation as a first-line therapy because, in his medical opinion, the need for quality of tears is of very high priority since they are being produced by the body. Other pharmacological agents, such as lubricants and immunomodulators, are unable to achieve the same level of nutrient density, as that capability doesn’t currently exist for artificial tears.
Dr. Kataria mentioned that neurostimulation can be a good recommendation for a subset of patients who struggle with instilling eye drops due to various forms of arthritis. She has found that this different mode of administration can improve compliance for patients with physical challenges.
Additionally, she emphasized that she is excited to learn more about how neurostimulation impacts the blink rate of dry eye patients, especially in patients with neurotrophic keratitis. She was also curious to explore the potential application of neurostimulation for corneal neuropathic pain.
Final thoughts on neurostimulation
Over his time prescribing neurostimulation treatments for DED, Dr. Fahmy observed that he has noticed many more patients are accepting of this therapeutic approach as it is considered less of an outlier compared to conventional topical medications. It has been particularly helpful for patients on polytherapy and contact lens patients.
Dr. Kataria is motivated to learn more about using Tyrvaya as an earlier or even first-line treatment for dry eye. She highlighted that if clinicians can reduce the medication burden on the ocular surface via neurostimulation, then there is the potential for significantly more application in DED treatment regimens.
