Patients with migraine may have more head and eye pain because of differences in the trigeminal system, with more activation of the trigeminal cervical complex.
A close relationship exists between migraine and the eye, said Kathleen B. Digre, MD. Patients with migraine often present to ophthalmologists rather than neurologists because of the accompanying ocular pain and visual symptoms and the frequency with which the disorder occurs—migraines occur more often than asthma and diabetes combined, said Dr. Digre, professor of neurology and ophthalmology, Moran Eye Center, University of Utah, Salt Lake City.
As such, important points for ophthalmologists to keep in mind are that migraine is very common; numerous unusual visual phenomena occur in migrainous brains; the dry eye symptoms in patients with migraine can be treated and improved, and the causes of the photophobia in these patients should be identified. Migraine also is associated with autonomic features of the conjunctiva, lid, and pupil.
Unique factors of migraine
“The visual quality of life in patients with migraines is not good,” Dr. Digre emphasized. When patients have chronic and episodic migraines—that is, they are affected 15 or more days a month and fewer than 15 days a month, respectively—the visual quality of life is similar to that in patients with Graves’ disease, idiopathic intracranial hypertension, and optic neuritis. Basic to an understanding of migraine is the recognition that in addition to pain these headaches represent a sensory processing disorder in the visual system.
“The brains of these patients are different,” Dr. Digre said. “Migraine is usually an inherited disorder.”
Compared with normal individuals, patients with migraine (but especially chronic migraine) may have more sensitivity to light, more visually enhanced phenomena, and more head and eye pain because of differences in the trigeminal system, with more activation of the trigeminal cervical complex.
“The fact that the eye should be a source of pain and migraine should not be surprising,” she said. The following cases of three patients demonstrate “typical” patients with migraine presenting to ophthalmologists.
Case 1: Dry eye, migraine connection
A 32-year-old woman presented with ocular pain, light and sound sensitivity, and nausea. Physical examination showed a low tear film score of 4 mm by Schirmer’s testing. Though dry eye syndrome is common in the general population, almost one-half of patients with Sjögren’s syndrome have migraine compared with the general population, Dr. Digre noted.
Recent studies of chronic migraine have identified lower Schirmer’s scores and higher Ocular Surface Disease Index scores in patients with migraine.
Most recently, studies have identified a mismatch between dry eye symptoms and migraine or fibromyalgia or other disorders with pain dysregulation. Dr. Digre noted this possibility because of the integrated lacrimal functional unit, which links the trigeminal system and the autonomic system, which produces the tears.
“The entire sensory part of the cornea, the eye, and the lacrimal unit is innervated by the trigeminal sensory system, including the trigeminal nucleus caudalis, which and its autonomic nervous system connections,” she said. “These autonomic areas then promote tear production.
“In chronic migraine, the trigeminal system becomes activated and central sensitization occurs,” Dr. Digre said. “When this happens, pain and dry eye symptoms can be felt even when no obvious signs of dry eye is present,” she said. “This can explain why dry eye symptoms and chronic eye pain may occur more frequently in those with chronic migraine.”
To determine the presence of corneal changes, Dr. Digre and her colleagues conducted a tear film study that included 19 patients with chronic migraine (Kinard et al. Headache. 2015;55:543-549). Patients completed a questionnaire regarding their dry eye symptoms. Investigators found that all chronic migraine patients had high dry eye scores compared with normal controls, despite normal basal tear film secretion and corneal sensitivity.
Importantly, corneal microscopy showed changes in nerve fiber density and nerve fiber length, which was confirmed recently in a study by Shetty et al. (Cornea. 2018;37:72–75). The causes of the corneal changes remain undetermined. Treatment of the dry eye symptoms is the mainstay in these patients. Whether this will improve chronic migraine in patients is not yet determined.
Case 2: Visual snow
A 17-year-old student presented with migraine and visual disturbances and a question about the possibility of permanent aura. He reported a family history of migraine and a personal history of migraine without aura or migraine with aura every 3 to 6 months. The patient described silvery lines in the vision that were always present; floating and squiggly lines when gazing at the sky or snow; and grainy vision all the time unassociated with headache.
In contrast, aura is a distinct neurologic event that progresses over time, it starts small and gets larger or vice versa, Dr. Digre said. This patient described symptoms that are typical for “visual snow,” which is more common than generally recognized, she noted. The proposed criteria for visual snow that were developed include: dynamic, continuous dots in the visual field for at least three months and the presence of at least two other visual phenomena and palinopsia, enhanced entoptic phenomenon, and at least one of the following: excessive floaters, or “self-light of the eye” or photopsia, photophobia, and nyctalopia.
“The symptoms are not typical migraine aura,” she said. These should be explained to the patient because visual snow is not a persistent aura. A normal eye examination can differentiate it from another disorder. Visual snow occurs in both sexes; 59% of patients have a history of migraine, but a history of some headache type is present in 87%. About 20% of patients have anxiety and depression, and about 25% of patients have had visual snow since childhood. A high presence of tinnitus is present (63%).
“Interestingly, positron emission tomography scans show changes in the supplementary visual cortex and cerebellum,” Dr. Digre said. Patients should be reassured that they are not “crazy.” Visual snow is noise in the visual system that is real.
Dr. Digre suggested that patients ignore the visual snow as much as possible. Medications can be ineffective. Lamotrigine, nortriptyline, carbamazepine, and sertraline have been reported to be beneficial. She suggested that patients use blue-yellow filters or FL-41 spectrum filters.
Case 3: Photophobia
A 35-year-old woman presented with severe photophobia of six months’ duration. She does not leave her house and keeps the curtains drawn. She has a history of migraine and wears sunglasses in the office. The ocular and neurologic examinations were normal.
There are dozens of causes of photophobia. To simplify the differential diagnosis, ophthalmologists can perform a few tests, according to Dr. Digre. The first consideration should be the central cause of the photophobia, such as a bitemporal field defect like a pituitary tumor, and then examine the patient for dry eye or corneal staining.
Next, instilling a drop of a topical anesthetic in the eye can help determine if the pain improves. If it does, a corneal neuropathy might be the culprit. The patient can be asked to describe the quality of his or her night vision, which might point to a retinal issue causing photophobia.
Next, if a reflex blepharospasm occurs after shining a light in the patient’s eye, reflexive blepharospasm is the cause of the photophobia. Finally, the patients should be asked directly about migraine. When considering the anatomic basis of photophobia, vision is not mandatory.
Patients with migraine who are legally blind—i.e., light perception or better vision—can have photophobia.
“The melanopsin pathway has greatly helped us because it is an important part of circadian rhythm and in the pupillary light reflex,” Dr. Digre said. “Animals with melanopsin and disrupted rods and code were still light sensitive. Those without melanopsin were found to be light insensitive.”
The pain in photophobia originates from the trigeminal system and the question arises about whether there is an association between melanopsin and the trigeminal system.
Investigators reported in Nature Neuro science (Noseda et al. 2010;13:239–345) that melanopsin was co-located with the trigeminal system, which was linked to the melanopsin pathway and the visual pathway in the
thalamus. This connection projected to the somatosensory cortex and the occipital cortex.
Dr. Digre explained that the study lead her to think about the presence of photophobia circuits. There is more than one way to experience photophobia, but trigeminal input is necessary for the discomfort. The dura, cornea, iris, and eye have input into the trigeminal system.
Other studies have indicated that the sympathetic pathway also modulates the system.
Going one step further, Dr. Digre discussed the potential for an emotional component in photophobia. A study of patients with migraine and chronic photophobia, those with migraine and episodic photophobia, and normal controls found that patients with chronic photophobia had significantly higher depression and anxiety scores than the other patients and controls (Llop et al. J Headache Pain. 2016;17:34).
These results indicated that there is an emotional component to photophobia, she said.
Treatment options include no treatment, dilating acutely inflamed eyes, reducing dark adaptation, treating the migraine, using more comfortable green light to examine patients, and using tinted lenses (gray, FL-41 filter, red contact lenses). The FL-41 tint blocks blue light and decreases light sensitivity and reduced symptoms by half in children, Dr. Digre noted.
Other treatments include treatment of dry eye and botulinum toxin injections, and use of anticonvulsant drugs may be helpful anecdotally. Dr. Digre suggested partnering with a neurologist to treat the migraine, depression, and anxiety and then working with an anesthesiologist/pain clinic to consider a sympathetic block.
“Ophthalmologists matter in the treatment of migraine and the eye,” she said. Dry eye treatment might help modulate the migraines. Ophthalmologists should understand the mismatch between dry eye and eye pain, and be part of the answer to diagnose and treat these patients. Ophthalmologists should know that visual snow exists and its association with migraine.
“Finally, photophobia should be considered a serious eye complaint and can be diagnosed and treated with the FL-41 tint or medication,” she concluded.
Kathleen B. Digre, MD
E: [email protected]
This article was adapted from Dr. Digre's presentation of the William F. Hoyt Lecture at the 2017 meeting of the American Academy of Ophthalmology. Dr. Digre has no proprietary interest in any aspect of this report.