Editor's Commentary

Have you ever tried to translate “transient receptor potential melastatin 8 agonist” into something digestible for your patient? Cue up the blank stare now, unless they happened to go to medical school. But tell them that it activates temperature sensors on your eye to increase tear production, you’re likely to get an understanding head no.

Explaining complex medical concepts to patients is likely one of the biggest challenges in health care. When patients don’t understand their diagnosis or treatment plan, it’s not just an issue of clarity; it’s a lost opportunity to build trust, ensure safety, and support compliance. It’s a delicate balance, though: Over-simplification can dilute the message so much that it loses meaning, and too much detail can overwhelm and confuse. A lack of understanding may cause a patient to take their condition too seriously (or not seriously enough) and could even result in avoidance of care altogether.

So how do we strike the right balance of delivering complicated scientific information to enable patients to make informed decisions about their own health without drowning them in medical jargon? I think it begins with empathy, lots of practice, and intentional communication. Working hard to identify gaps in understanding before they turn into problems is important, and using visual aids, metaphors, and analogies can help. The next time you have a challenging concept or treatment plan to deliver, ask your patient to explain it back to you in their own words (this is known as the “teach-back method”) to verify understanding. It’s important to do this in a way that isn’t perceived as a “quiz” but more of a double-check that you did your job correctly. 

Health care is most effective when it’s a partnership. Of course, for any partnership to be successful, all parties need to speak the same language. Achieving clear, compassionate, two-way communication is not just a courtesy; it is a requirement for patient empowerment which usually leads to improved health outcomes. Win-win.

Amber Gaume Giannoni, OD, FAAO

Editor

Clinician’s Corner

Jaclyn Garlich, OD, FAAO
Glance by Eyes on Eyecare, President
Envision Optometry, Owner

Explaining Alternate Tear Production Pathways to Patients

As optometrists, we often encounter patients with dry eye who feel frustrated after trying multiple therapies with little relief. Despite the expanding arsenal of treatments—ranging from over-the-counter artificial tears to prescription immunomodulators and anti-inflammatory and anti-evaporative drops—many of us have realized that one thing remains difficult to replicate: the body’s own natural tears.

Patients may not fully realize just how important—and complex—tears really are. Despite being a tiny amount of liquid, they represent a remarkably complex blend of electrolytes, mucins, proteins, and lipids, all of which are crucial for ocular surface health and comfort.

The body's ability to produce these basal tears involves stimulation of an intricate neural network. This is where newer pharmaceutical options such as varenicline nasal spray—and, in the near future, acoltremon—offer a novel and elegant approach. While varenicline is delivered through the nose and acoltremon is delivered topically, both work by activating the lacrimal functional unit (LFU), which modulates the basal tear response. The result? Endogenous tear production initiated through the body’s natural reflex arc.

As complex as this sounds, we need to find a way to simplify this message to a patient. Effectively explaining this mechanism to patients is key to improving understanding, compliance, and outcomes.

Some patients want the “science,” but most appreciate a quick, relatable explanation. I like to start with messages that are short and to the point, and then I can elaborate if the patient desires. One way to start: “This medication activates nerve receptors in the nose/on the eye that stimulate your own natural tear production. It tells your body to produce more tears naturally, using a reflex that’s already built into your system.”

From there, I can tailor the level of detail to each patient’s curiosity. By breaking it down into relatable language and building trust in the mechanism, we can empower our patients, improve compliance, and help them feel like they’re doing more than just adding drops—they’re tapping into their body’s own healing potential.

Research Update: 
Commentary on Abstract of the Week

Blair Lonsberry, MS, OD, MEd, FAAO
American Board of Optometry, Diplomate
Pacific University College of Optometry, Professor of Optometry

Sensory innervation of the ocular surface is responsible for responding to external stimuli to maintain corneal integrity, blinking, and tear homeostasis. The innervation of the cornea has traditionally been divided into three categories of peripheral receptors: mechanonociceptors, which are responsible for detecting dangerous mechanical stimuli; cold-thermosensitive receptors, which are activated by cold temperatures, dryness, and tear hyperosmolarity; and polymodal nociceptors, which detect touch, chemical stimulation, and noxious heating.

Most studies regarding the ocular surface sensory system have focused on the peripheral innervation with very little research delving into central nervous system (CNS) involvement. The goal of this study was to determine the somatosensory representation of the ocular surface in the CNS, including the peripheral ophthalmic branch of the trigeminal ganglion (TG), the central somatosensory thalamus (Th), and primary somatosensory cortex (S1).

Utilizing anesthetized rats, single and multi-unit electrophysiological recordings were obtained when various stimuli were applied to the ocular surface. The stimulation consisted of the topical application of 20 μL saline drops at different temperatures (range 10°–60°C, inducing ocular surface temperature changes between −20° and +30°C with respect to a basal ocular surface temperature of 30°C), with 30-second intervals between stimuli.

To record the neurons, the examiners used the stereotaxic coordinates for neurons innervating the TG, Th, and S1 that had been determined from previous studies. Extracellular recordings were made using tungsten electrodes, which were then amplified (×500) and filtered in DC mode (0–3 kHz) using a preamplifier, filter, and amplifier sequential circuit. Analog signals were then converted to digital for analysis. Recordings were contralateral for S1 and Th and ipsilateral for TG with respect to the stimulated eye.

The data demonstrated that the TG, Th, and S1 responses to the same stimulus modality are different in temporal profile and magnitude. Importantly, each sensory modality was processed in a different way inside the same structure of the sensory pathway, especially in the Th and cortex (Cx). Additionally, the percentage of single neurons with multimodal responses was increased from the TG to Th, reaching the highest in Cx.

The authors concluded that the sensory modalities responsible for stimulating the ocular surface S are processed differently from the periphery (TG) to the central structures of the somatosensory system, (Th and Cx), which demonstrates an increased complexity of response profiles and multimodal integration. These results could help us better understand why changes on the ocular surface seem to cause variable somatosensory responses.

The mechanisms involved remain poorly understood, although it appears that ocular surface changes result in plastic changes of the thalamocortical circuits, such as those reported for dry eye disease in the brainstem.

Abstract

Ocular surface information seen from the somatosensory thalamus and cortex

Velasco E, Zaforas M, Acosta MC, Gallar J, Aguilar J. Ocular surface information seen from the somatosensory thalamus and cortex. J Physiol. 2024;602:1405–1426. doi:10.1113/JP285008

Ocular Surface (OS) somatosensory innervation detects external stimuli producing perceptions, such as pain or dryness, the most relevant symptoms in many OS pathologies. Nevertheless, little is known about the central nervous system circuits involved in these perceptions, and how they integrate multimodal inputs in general. Here, we aim to describe the thalamic and cortical activity in response to OS stimulation of different modalities. Electrophysiological extracellular recordings in anaesthetized rats were used to record neural activity, while saline drops at different temperatures were applied to stimulate the OS. Neurons were recorded in the ophthalmic branch of the trigeminal ganglion (TG, 49 units), the thalamic VPM-POm nuclei representing the face (Th, 69 units) and the primary somatosensory cortex (S1, 101 units). The precise locations for Th and S1 neurons receiving OS information are reported here for the first time. Interestingly, all recorded nuclei encode modality both at the single neuron and population levels, with noxious stimulation producing a qualitatively different activity profile from other modalities. Moreover, neurons responding to new combinations of stimulus modalities not present in the peripheral TG subsequently appear in Th and S1, being organized in space through the formation of clusters. Besides, neurons that present higher multimodality display higher spontaneous activity. These results constitute the first anatomical and functional characterization of the thalamocortical representation of the OS. Furthermore, they provide insight into how information from different modalities gets integrated from the peripheral nervous system into the complex cortical networks of the brain.

KEY POINTS: Anatomical location of thalamic and cortical ocular surface representation. Thalamic and cortical neuronal responses to multimodal stimulation of the ocular surface. Increasing functional complexity along trigeminal neuroaxis. Proposal of a new perspective on how peripheral activity shapes central nervous system function.

Pipeline

Patrick Vollmer, OD FAAO
Medical Director, Charlotte Ophthalmic Research
Vita Eye Clinic
Core, Inc

Using Acoltremon to Treat Dry Eye Disease

In an exciting update for patients with dry eye, Alcon’s AR-15512 (acoltremon ophthalmic solution) 0.003% has recently shown a positive long-term effect in treating the signs and symptoms of dry eye disease (DED).¹ For those unfamiliar, acoltremon is a first-in-its-class investigational product designed to treat DED by its mechanism of action. Acoltremon is a topical transient receptor potential melastatin 8 agonist (TRPM8) and works via the simulation of TRPM8 receptors located on the sensory nerves of the cornea and eyelids.

TRPM8 receptors detect temperature and osmolarity changes on the ocular surface that, when activated, generate a “cooling sensation.” This triggers the trigeminal nerve to produce basal tears. Using the same mechanism, TRPM8 channels also regulate ocular blink rate. Problems with TRPM8 receptors can cause pain on the surface of the eye, but stimulating TRPM8 lowers pro-inflammatory substances that cause inflammation.²

Touting a favorable safety and tolerability profile during phase-3 pivotal trials (COMET-1 and COMET-2), acoltremon use showed statistically significant improvements in DED signs and symptoms when dosed twice a day over a 12-week period. Traditionally, treatments for DED have focused on increasing lubrication and reducing inflammation. Alcon’s AR-15512 new mechanism of action would represent a revolutionary approach for the treatment of DED.

References

1. Delaney-Gesing A. Long-term data finds acoltremon 0.003% increases tear production in DED. Eyes on Eyecare. https://glance.eyesoneyecare.com/stories/2025-04-25/long-term-data-finds-acoltremon-0-003-increases-tear-production-in-ded/ Published April 25, 2025.
2. Powell W. AR-15512, a novel topical drug candidate for dry eye disease. Touch Ophthalmology. https://touchophthalmology.com/corneal-and-external-disorders/journal-articles/ar-15512-a-novel-topical-drug-candidate-for-dry-eye-disease/ Published October 10, 2024.