Why the Eye Should Be a Focus When Treating Migraine

 

SAN DIEGO—Among patients with migraine, eye-related symptoms such as dry eyes and photophobia are common and treatable, said Kathleen B. Digre, MD, Professor of Neurology and Ophthalmology at the University of Utah in Salt Lake City. Neurologists should treat eye-related conditions “in hopes that we can improve our patients’ migraine,” Dr. Digre said at the 58th Annual Scientific Meeting of the American Headache Society.

There are various ways the eye may contribute to migraine and headache. The first division of the trigeminal nerve innervates the eye as well as the dura mater, which may play a role in migraine pain, Dr. Digre said. Trigeminal innervation is involved in tear film production. In addition, the cornea has the densest sensory nerve innervation in the body. “Think about the eye every time you see a patient with severe migraine in the clinic,” she said.

Dry Eyes

About 20% to 30% of people over age 45 have dry eyes. Dry eyes are more common in women than in men. Reading, computer use, and watching television may worsen dry eye symptoms due to reduced blinking during those activities. Dry climate, hormones, and certain medications used for migraine, such as amitriptyline and antihistamines, can cause or worsen dry eye symptoms. About 45% of people with Sjögren’s syndrome, a condition that causes dry eyes, have migraine. Furthermore, dry eyes are associated with photophobia, Dr. Digre said.

Koktekir et al in 2012 examined tear film function in patients with episodic migraine versus controls and found that migraineurs had significantly more tear film dysfunction, as measured by Schirmer’s test, tear film breakup time, lissamine green stain, and the Ocular Surface Disease Index.

In a case–control study published in Headache in 2015, Krista I. Kinard, MD, Adjunct Assistant Professor of Ophthalmology at the University of Utah, Dr. Digre, and colleagues examined 19 patients with chronic migraine and 30 controls. Tear film breakup time, basal tear cell secretion, and corneal sensitivity did not differ between the groups. Using corneal microscopy, however, the researchers found that controls had denser nerve fibers than patients with chronic migraine. On the Dry Eye Questionnaire, all patients with chronic migraine scored above 6, a result consistent with dry eye syndrome, whereas controls scored less than 3, as expected. Future research should evaluate whether dry eye symptoms result from the migraine process or whether dry eye symptoms may lead to chronic migraine by continuous stimulation, Dr. Digre said.

Therapeutic Options

Over-the-counter artificial tears, gels, and ointments may be safe and effective treatments for dry eyes. A review published in 2016 found that in two trials, polyacrylic acid-based artificial tears more effectively treated dry eye symptoms than polyvinyl alcohol-based artificial tears. Dr. Digre avoids preservatives in artificial tears because some people are sensitive to them. Oral flaxseed oil or fish oil also may help patients. If symptoms do not improve, an ophthalmologist may consider more aggressive dry eye therapy, such as punctal plugs, she said.

Photophobia

Photophobia is one of the major diagnostic criteria of migraine, and migraine is the most common cause of photophobia, Dr. Digre said. Ninety percent of people with migraine have photophobia during a migraine attack. Ocular inflammation, including dry eye, retinal disease, and cone dystrophy, is associated with photophobia. Certain brain disorders, including meningitis, pituitary tumors, and progressive supranuclear palsy, can cause photophobia. In addition, some psychiatric conditions, such as depression, and certain medications, including stimulants, have been associated with photophobia.

Photophobia has an anatomic basis, and patients without vision may still be light sensitive, Dr. Digre said. The discovery of the melanopsin pathway, a pathway of intrinsically photoactive retinal ganglion cells that function when exposed to light and inform circadian rhythm, was a breakthrough in understanding photophobia, she said.

Delwig et al in 2012 reported that when newborn mice with melanopsin-expressing intrinsically photoactive retinal ganglion cells were exposed to light, the mice vocalized in a way that is similar to when mice are distressed by having to leave the litter. Mice without melanopsin do not exhibit this same aversive behavior, Dr. Digre said. Jones et al in 2013 described a melanopsin antagonist that reverses light aversion in mice.

Light sensitivity may be associated with depression and anxiety. To assess the prevalence of anxiety and depression symptoms in migraineurs with and without interictal photophobia, Llop et al studied 16 patients with episodic migraine who had interictal photophobia, 16 patients with episodic migraine who had photophobia only during migraine attacks, and 16 controls. Migraineurs with interictal photophobia had higher scores on the Beck Depression Inventory and Beck Anxiety Inventory, compared with subjects without interictal photophobia.

 

Treating Light Sensitivity

Tinted lenses may help patients with migraine and photophobia. Good et al in 1991 published a study that included 20 children with migraine. Patients wore glasses with FL-41–tinted lenses (ie, a rose-colored tint) or blue-tinted lenses. Patients with FL-41–tinted lenses had reduced headache frequency at four months, whereas patients with blue-tinted lenses did not experience a sustained reduction in headache frequency.

Patients with photophobia should not keep themselves in the dark. “Every single person who comes in with three layers of sunglasses, you have to tell them that the more you stay in the dark, the worse this is going to get,” Dr. Digre said. “We have to … slowly peel off the sunglasses, lift up the shades, and start getting used to more light.”

Botulinum toxin, sympathetic nerve blocks, gabapentin, and melatonin have been used in people with photophobia. Importantly, physicians should treat any underlying psychiatric or neurologic condition, including migraine, that may be driving patients’ light sensitivity, Dr. Digre said.

—Jake Remaly

Suggested Reading

Delwig A, Logan AM, Copenhagen DR, Ahn AH. Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice. PLoS One. 2012;7(9):e43787.

Good PA, Taylor RH, Mortimer MJ. The use of tinted glasses in childhood migraine. Headache. 1991;31(8):533-536.

Jones KA, Hatori M, Mure LS, et al. Small-molecule antagonists of melanopsin-mediated phototransduction. Nat Chem Biol. 2013;9(10):630-635.

Kinard KI, Smith AG, Singleton JR, et al. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015;55(4):543-549.

Koktekir BE, Celik G, Karalezli A, Kal A. Dry eyes and migraines: is there really a correlation? Cornea. 2012;31(12):1414-1416.

Llop SM, Frandsen JE, Digre KB, et al. Increased prevalence of depression and anxiety in patients with migraine and interictal photophobia. J Headache Pain. 2016;17:34.

Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci. 2010;13(2):239-245.

Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016 Feb 23;2:CD009729.

 

SAN DIEGO—Among patients with migraine, eye-related symptoms such as dry eyes and photophobia are common and treatable, said Kathleen B. Digre, MD, Professor of Neurology and Ophthalmology at the University of Utah in Salt Lake City. Neurologists should treat eye-related conditions “in hopes that we can improve our patients’ migraine,” Dr. Digre said at the 58th Annual Scientific Meeting of the American Headache Society.

There are various ways the eye may contribute to migraine and headache. The first division of the trigeminal nerve innervates the eye as well as the dura mater, which may play a role in migraine pain, Dr. Digre said. Trigeminal innervation is involved in tear film production. In addition, the cornea has the densest sensory nerve innervation in the body. “Think about the eye every time you see a patient with severe migraine in the clinic,” she said.

Dry Eyes

About 20% to 30% of people over age 45 have dry eyes. Dry eyes are more common in women than in men. Reading, computer use, and watching television may worsen dry eye symptoms due to reduced blinking during those activities. Dry climate, hormones, and certain medications used for migraine, such as amitriptyline and antihistamines, can cause or worsen dry eye symptoms. About 45% of people with Sjögren’s syndrome, a condition that causes dry eyes, have migraine. Furthermore, dry eyes are associated with photophobia, Dr. Digre said.

Koktekir et al in 2012 examined tear film function in patients with episodic migraine versus controls and found that migraineurs had significantly more tear film dysfunction, as measured by Schirmer’s test, tear film breakup time, lissamine green stain, and the Ocular Surface Disease Index.

In a case–control study published in Headache in 2015, Krista I. Kinard, MD, Adjunct Assistant Professor of Ophthalmology at the University of Utah, Dr. Digre, and colleagues examined 19 patients with chronic migraine and 30 controls. Tear film breakup time, basal tear cell secretion, and corneal sensitivity did not differ between the groups. Using corneal microscopy, however, the researchers found that controls had denser nerve fibers than patients with chronic migraine. On the Dry Eye Questionnaire, all patients with chronic migraine scored above 6, a result consistent with dry eye syndrome, whereas controls scored less than 3, as expected. Future research should evaluate whether dry eye symptoms result from the migraine process or whether dry eye symptoms may lead to chronic migraine by continuous stimulation, Dr. Digre said.

Therapeutic Options

Over-the-counter artificial tears, gels, and ointments may be safe and effective treatments for dry eyes. A review published in 2016 found that in two trials, polyacrylic acid-based artificial tears more effectively treated dry eye symptoms than polyvinyl alcohol-based artificial tears. Dr. Digre avoids preservatives in artificial tears because some people are sensitive to them. Oral flaxseed oil or fish oil also may help patients. If symptoms do not improve, an ophthalmologist may consider more aggressive dry eye therapy, such as punctal plugs, she said.

Photophobia

Photophobia is one of the major diagnostic criteria of migraine, and migraine is the most common cause of photophobia, Dr. Digre said. Ninety percent of people with migraine have photophobia during a migraine attack. Ocular inflammation, including dry eye, retinal disease, and cone dystrophy, is associated with photophobia. Certain brain disorders, including meningitis, pituitary tumors, and progressive supranuclear palsy, can cause photophobia. In addition, some psychiatric conditions, such as depression, and certain medications, including stimulants, have been associated with photophobia.

Photophobia has an anatomic basis, and patients without vision may still be light sensitive, Dr. Digre said. The discovery of the melanopsin pathway, a pathway of intrinsically photoactive retinal ganglion cells that function when exposed to light and inform circadian rhythm, was a breakthrough in understanding photophobia, she said.

Delwig et al in 2012 reported that when newborn mice with melanopsin-expressing intrinsically photoactive retinal ganglion cells were exposed to light, the mice vocalized in a way that is similar to when mice are distressed by having to leave the litter. Mice without melanopsin do not exhibit this same aversive behavior, Dr. Digre said. Jones et al in 2013 described a melanopsin antagonist that reverses light aversion in mice.

Light sensitivity may be associated with depression and anxiety. To assess the prevalence of anxiety and depression symptoms in migraineurs with and without interictal photophobia, Llop et al studied 16 patients with episodic migraine who had interictal photophobia, 16 patients with episodic migraine who had photophobia only during migraine attacks, and 16 controls. Migraineurs with interictal photophobia had higher scores on the Beck Depression Inventory and Beck Anxiety Inventory, compared with subjects without interictal photophobia.

 

Treating Light Sensitivity

Tinted lenses may help patients with migraine and photophobia. Good et al in 1991 published a study that included 20 children with migraine. Patients wore glasses with FL-41–tinted lenses (ie, a rose-colored tint) or blue-tinted lenses. Patients with FL-41–tinted lenses had reduced headache frequency at four months, whereas patients with blue-tinted lenses did not experience a sustained reduction in headache frequency.

Patients with photophobia should not keep themselves in the dark. “Every single person who comes in with three layers of sunglasses, you have to tell them that the more you stay in the dark, the worse this is going to get,” Dr. Digre said. “We have to … slowly peel off the sunglasses, lift up the shades, and start getting used to more light.”

Botulinum toxin, sympathetic nerve blocks, gabapentin, and melatonin have been used in people with photophobia. Importantly, physicians should treat any underlying psychiatric or neurologic condition, including migraine, that may be driving patients’ light sensitivity, Dr. Digre said.

—Jake Remaly

Suggested Reading

Delwig A, Logan AM, Copenhagen DR, Ahn AH. Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice. PLoS One. 2012;7(9):e43787.

Good PA, Taylor RH, Mortimer MJ. The use of tinted glasses in childhood migraine. Headache. 1991;31(8):533-536.

Jones KA, Hatori M, Mure LS, et al. Small-molecule antagonists of melanopsin-mediated phototransduction. Nat Chem Biol. 2013;9(10):630-635.

Kinard KI, Smith AG, Singleton JR, et al. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015;55(4):543-549.

Koktekir BE, Celik G, Karalezli A, Kal A. Dry eyes and migraines: is there really a correlation? Cornea. 2012;31(12):1414-1416.

Llop SM, Frandsen JE, Digre KB, et al. Increased prevalence of depression and anxiety in patients with migraine and interictal photophobia. J Headache Pain. 2016;17:34.

Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci. 2010;13(2):239-245.

Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016 Feb 23;2:CD009729.

 

SAN DIEGO—Among patients with migraine, eye-related symptoms such as dry eyes and photophobia are common and treatable, said Kathleen B. Digre, MD, Professor of Neurology and Ophthalmology at the University of Utah in Salt Lake City. Neurologists should treat eye-related conditions “in hopes that we can improve our patients’ migraine,” Dr. Digre said at the 58th Annual Scientific Meeting of the American Headache Society.

There are various ways the eye may contribute to migraine and headache. The first division of the trigeminal nerve innervates the eye as well as the dura mater, which may play a role in migraine pain, Dr. Digre said. Trigeminal innervation is involved in tear film production. In addition, the cornea has the densest sensory nerve innervation in the body. “Think about the eye every time you see a patient with severe migraine in the clinic,” she said.

Dry Eyes

About 20% to 30% of people over age 45 have dry eyes. Dry eyes are more common in women than in men. Reading, computer use, and watching television may worsen dry eye symptoms due to reduced blinking during those activities. Dry climate, hormones, and certain medications used for migraine, such as amitriptyline and antihistamines, can cause or worsen dry eye symptoms. About 45% of people with Sjögren’s syndrome, a condition that causes dry eyes, have migraine. Furthermore, dry eyes are associated with photophobia, Dr. Digre said.

Koktekir et al in 2012 examined tear film function in patients with episodic migraine versus controls and found that migraineurs had significantly more tear film dysfunction, as measured by Schirmer’s test, tear film breakup time, lissamine green stain, and the Ocular Surface Disease Index.

In a case–control study published in Headache in 2015, Krista I. Kinard, MD, Adjunct Assistant Professor of Ophthalmology at the University of Utah, Dr. Digre, and colleagues examined 19 patients with chronic migraine and 30 controls. Tear film breakup time, basal tear cell secretion, and corneal sensitivity did not differ between the groups. Using corneal microscopy, however, the researchers found that controls had denser nerve fibers than patients with chronic migraine. On the Dry Eye Questionnaire, all patients with chronic migraine scored above 6, a result consistent with dry eye syndrome, whereas controls scored less than 3, as expected. Future research should evaluate whether dry eye symptoms result from the migraine process or whether dry eye symptoms may lead to chronic migraine by continuous stimulation, Dr. Digre said.

Therapeutic Options

Over-the-counter artificial tears, gels, and ointments may be safe and effective treatments for dry eyes. A review published in 2016 found that in two trials, polyacrylic acid-based artificial tears more effectively treated dry eye symptoms than polyvinyl alcohol-based artificial tears. Dr. Digre avoids preservatives in artificial tears because some people are sensitive to them. Oral flaxseed oil or fish oil also may help patients. If symptoms do not improve, an ophthalmologist may consider more aggressive dry eye therapy, such as punctal plugs, she said.

Photophobia

Photophobia is one of the major diagnostic criteria of migraine, and migraine is the most common cause of photophobia, Dr. Digre said. Ninety percent of people with migraine have photophobia during a migraine attack. Ocular inflammation, including dry eye, retinal disease, and cone dystrophy, is associated with photophobia. Certain brain disorders, including meningitis, pituitary tumors, and progressive supranuclear palsy, can cause photophobia. In addition, some psychiatric conditions, such as depression, and certain medications, including stimulants, have been associated with photophobia.

Photophobia has an anatomic basis, and patients without vision may still be light sensitive, Dr. Digre said. The discovery of the melanopsin pathway, a pathway of intrinsically photoactive retinal ganglion cells that function when exposed to light and inform circadian rhythm, was a breakthrough in understanding photophobia, she said.

Delwig et al in 2012 reported that when newborn mice with melanopsin-expressing intrinsically photoactive retinal ganglion cells were exposed to light, the mice vocalized in a way that is similar to when mice are distressed by having to leave the litter. Mice without melanopsin do not exhibit this same aversive behavior, Dr. Digre said. Jones et al in 2013 described a melanopsin antagonist that reverses light aversion in mice.

Light sensitivity may be associated with depression and anxiety. To assess the prevalence of anxiety and depression symptoms in migraineurs with and without interictal photophobia, Llop et al studied 16 patients with episodic migraine who had interictal photophobia, 16 patients with episodic migraine who had photophobia only during migraine attacks, and 16 controls. Migraineurs with interictal photophobia had higher scores on the Beck Depression Inventory and Beck Anxiety Inventory, compared with subjects without interictal photophobia.

 

Treating Light Sensitivity

Tinted lenses may help patients with migraine and photophobia. Good et al in 1991 published a study that included 20 children with migraine. Patients wore glasses with FL-41–tinted lenses (ie, a rose-colored tint) or blue-tinted lenses. Patients with FL-41–tinted lenses had reduced headache frequency at four months, whereas patients with blue-tinted lenses did not experience a sustained reduction in headache frequency.

Patients with photophobia should not keep themselves in the dark. “Every single person who comes in with three layers of sunglasses, you have to tell them that the more you stay in the dark, the worse this is going to get,” Dr. Digre said. “We have to … slowly peel off the sunglasses, lift up the shades, and start getting used to more light.”

Botulinum toxin, sympathetic nerve blocks, gabapentin, and melatonin have been used in people with photophobia. Importantly, physicians should treat any underlying psychiatric or neurologic condition, including migraine, that may be driving patients’ light sensitivity, Dr. Digre said.

—Jake Remaly

Suggested Reading

Delwig A, Logan AM, Copenhagen DR, Ahn AH. Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice. PLoS One. 2012;7(9):e43787.

Good PA, Taylor RH, Mortimer MJ. The use of tinted glasses in childhood migraine. Headache. 1991;31(8):533-536.

Jones KA, Hatori M, Mure LS, et al. Small-molecule antagonists of melanopsin-mediated phototransduction. Nat Chem Biol. 2013;9(10):630-635.

Kinard KI, Smith AG, Singleton JR, et al. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015;55(4):543-549.

Koktekir BE, Celik G, Karalezli A, Kal A. Dry eyes and migraines: is there really a correlation? Cornea. 2012;31(12):1414-1416.

Llop SM, Frandsen JE, Digre KB, et al. Increased prevalence of depression and anxiety in patients with migraine and interictal photophobia. J Headache Pain. 2016;17:34.

Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci. 2010;13(2):239-245.

Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016 Feb 23;2:CD009729.