Understanding the Relationship Between Dry Eye and Migraine

In a review published in Eye and Brain, researchers outlined the link between dry eye and migraine, their possible shared pathophysiology, and therapies targeting similar pathophysiological mechanisms.

Both dry eye and migraine are prevalent in the general population, and in recent years, studies have chronicled the comorbidity of the 2 conditions. Several investigations have linked depression and anxiety to dry eye; some individuals with the condition also exhibit sleep abnormalities. These comorbidities are also frequent among migraineurs.

“The symptoms of dry eye are variable and can include sensations of dryness, grittiness, burning and stinging,” the authors wrote. “Individuals may also report that these sensations are spontaneous and/or evoked by wind or light. Others complain of visual phenomena, such as blurry or fluctuating vision.”

Researchers searched PubMed for scientific articles concerning dry eye and migraine and found that the conditions are often comorbid. One Korean population-based cross-sectional study found the frequency of dry eye diagnosis was higher among migraineurs. Additional studies yielded similar results, finding the association strongest among women 65 years and older.

Several studies have also found that dry eye symptoms, as opposed to dry eye signs, are associated with migraine. Dry eye characteristics appear to be more prevalent among migraineurs with aura compared with those without aura, and among patients with longer lifetime duration of migraine. However, definitions of dry eye were not consistent among all studies and migraine criteria were not always clearly outlined.

The presence of photophobia, or light-induced neurological symptoms, marks an additional common feature between migraine and dry eye. Photophobia can usually emerge as increased sensitivity to light or glare, intensification of headache, and ocular pain or discomfort. In addition, the presence of photophobia in both dry eye and migraine has implications for shared pathophysiology, authors explained.

Several explanations of the neural circuitry underlying photophobia involve light-evoked signals in rod and cone cells transmitted to retinal ganglion cells (RGCs) via amacrine and bipolar cells, light-sensitive neurons in the posterior thalamus which receive input from photosensitive RGCs and dural trigeminal afferents, or involve the hypothalamus, retinal rod and cone cells, and the iris.

When it comes to shared underlying pathophysiology, “One unifying theory is that dry eye symptoms and migraine involve abnormal peripheral trigeminal nerve activation with subsequent peripheral and central sensitization,” the researchers wrote.

Studies suggest that dry eye symptoms and migraine pain are driven in part by peripheral sensitization, as corneal nerve alterations have been documented in both conditions. According to the authors, photophobia has also been linked to peripheral corneal nerve abnormalities.

Central nerve abnormalities have been exhibited in migraine and dry eye, but more imaging studies are needed to validate findings.

Research indicates that inflammation is an important contributor to peripheral and central nerve abnormalities in the conditions. In particular, calcitonin gene-related peptide (CGRP), a neuropeptide involved in neurogenic inflammation, has been associated with changes in nerve function in dry eye and migraine. CGRP can also induce light sensitivity.

“The overlap between dry eye and migraine has potential implications in the evaluation and treatment of individuals with these 2 diseases,” authors said, noting:

• Eye care providers should ask individuals with dry eye about comorbid headache, and primary care doctors and neurologists should ask individuals with migraine about symptoms of dry eye.
• Eye care providers should think about nerve status when evaluating an individual with dry eye symptoms, including assessing for ocular pain via standardized questionnaires and evaluating nerve structure and function clinically.

Targeting tear dysfunction is considered first-line treatment for managing dry eye. However, the researchers noted that when this approach does not sufficiently relieve symptoms, providers should consider therapies targeting nerve dysfunction.

Overall information provided in the review “can be used to better understand pathophysiological mechanisms and develop targeted treatments by applying therapies successful in reducing migraine pain to dry eye,” the researchers concluded.

Reference

Baksh BS, Garcia JC, Galor A. Exploring the link between dry eye and migraine: from eye to brain. Eye Brain. Published online March 4, 2021. doi:10.2147/EB.S234073