When dry eye treatments are not working for your patient’s symptoms or the anterior segment exam looks normal, you must ask yourself: What if the symptoms are secondary to a neurologic dysfunction in pain perception?
Most optometric treatment of dry eye involves lubrication, eyelid hygiene, and oral supplementation, with the goals of reducing ocular surface inflammation and re-establishing tear film homeostasis. Jacqueline Theis, OD, FAAO, who practices in Richmond, VA, described how those treatment options can fail in patients who present with dry eye symptoms, especially severe ocular surface pain, but no signs of ocular surface dysfunction or eyelid margin disease.
She posed these questions at 2023 American Optometric Association (AOA) Optometry’s Meeting. When dry eye treatments are not working for your patient’s symptoms or the anterior segment exam looks normal, you must ask yourself: What if the symptoms are secondary to a neurologic dysfunction in pain perception? What if the symptoms are actually secondary to an underlying neurologic disease or co-morbidity and I am treating the wrong thing? Dry eye accompanies a number of different disease processes, and Theis described how to differentiate garden variety dry eye from a neurologic cause or neuropathic or musculoskeletal eye pain.
There are 2 types of pain, both of which can be present in dry eye disease. Nociceptive pain, which results from tissue damage and inflammation leading to activation of nociceptors, is usually transient, and the most common type of primary dry eye related pain. The cornea contains nociceptors that trigger pain in response to touch, heat, cold, chemical irritants, bacterial toxins, pH, and temperature changes. Thus, the ocular surface insults that can trigger pain symptoms can include infection, inflammation, trauma, adverse environmental conditions, abnormal ocular anatomy, and high tear osmolarity.
In contrast, neuropathic pain results from a lesion or disease affecting the somatosensory system. Thus, a patient can have the perception of corneal pain, when the lesion itself is occurring in the second- or third-order neurons that are beyond the eye, located in the neck, brainstem, and brain. This pain is usually chronic and the etiology can be degenerative, traumatic, infectious, metabolic, or toxic.
Theis discussed the ocular neuro-sensory pathways and how pain develops and is transmitted, and how not treating dry eye early on in the disease can lead to pain desensitization and ultimately neuropathic eye pain.
It can occur in seemingly unrelated circumstances, Theis explained.
Recent studies have shown that dry eye and ocular pain are more common in patients with a history of traumatic brain injury than in the general population. Dry eye is also common in migraine and other pain disorders, ie, chronic regional pain syndrome and fibromyalgia as well as psychiatric conditions such as depression and anxiety.
Additionally, dry eye can be caused by sleep disorders including sleep apnea, but also just general sleep deprivation. One study found that just 2 nights of sleep deprivation can compromise the lacrimal gland and induces dry eye. Theis explained that staying up all night can induce tear hyperosmolarity and reduce tear secretion.
All of these conditions are comorbidities with traumatic brain injury. Sometimes the best way to treat dry eye in these patients is to refer them to other multi-disciplinary providers to treat the underlying conditions.
Interestingly, she noted, dry eye, traumatic brain injury, migraine, fibromyalgia, and psychiatric disorders all have one thing in common: photophobia. Studies have hypothesized connections between the intrinsically photosensitive retinal ganglion cells and symptoms seen in patients with traumatic brain injuries—headache, ocular pain, light sensitivity, and sleep disruption—as having a possible common pathophysiological etiology.
She also related that dry eye evaluation needs to go beyond the ocular surface to include eyelid evaluation for both eyelid margin disease but also blink rate, which is neurologically driven. The average blink rate is about 15-20 blinks per minute. Blink rate can decline with near activities like computer and reading, but can significantly decline in patients who have lesions in the basal ganglia leading to reduced dopamine secretion.
One of the first presentations of Parkinson disease is a reduced blink rate, which can lead to dry eye symptoms for these patients. In fact, dry eye disease is present in from 53-60% of patients with Parkinson disease. The pathophysiology of dry eye in Parkinson disease is multifaceted and involves both a decreased blink rate, leading to reduced lipid distribution, and increased aqueous evaporation and decreased tear production, resulting from abnormal autonomic innervation to the lacrimal gland. While you may (and should) treat these patients with topical lubrication, you should also encourage patients to talk to their care team about starting or adjusting systemic dopamine medications to see meaningful change in their dry eye symptoms.
Differentiating pre-clinical dry eye and neuropathic eye pain can be difficult. Clinicians can suspect if the pain is neuropathic in nature based on chronicity and persistence of pain despite topical lubrication. Neuropathic ocular pain is more likely to be chronic, and patients describe pain with more neurological descriptors such as hot, searing, burning, tingling, and electric, versus more common nociceptive symptoms of itch and foreign body sensation. Patients with chronic neuropathic pain have an exaggerated pain response to normal stimuli due to reduced pain thresholds of their nociceptors, known as hyperalgesia, so many of them may have a subtype of photophobia called photoallodynia, where they have pain from a light stimulus that should not elicit pain—like normal room lighting.
In office, you can do a proparacaine challenge, where you instill proparacaine into the eye and see if their eye pain goes away. If their eye pain persists, you should be suspicious of an underlying neuropathic pain component.
Treatment options for neuropathic ocular pain are in their infancy. One should always start with ocular surface treatments and anti-inflammatories. The key is to continue to follow up with the patient, reassure them that it may take trial and error to figure out what works best for them, and use a stepwise approach. If your typical battery does not work, consider neuro-regenerative therapies like autologous serum tears and neurotrophic growth factors. Recent studies, especially in refractory photophobia, have supported the use of Botox, which is thought to decrease signaling through primary trigeminal afferents and may decrease the release of inflammatory mediators to help both photophobia and ocular pain.
If chronic pain persists, clinicians should consider referral for further pain and psychiatric management and possible systemic treatment options such as gabapentioids, opiates, anti-epileptics, antidepressants, nerve blocks, and electrical neurostimulation therapies. Chronic pain is a physical and emotional condition that requires compassion and often a multi-disciplinary approach.