Secondary Logo

Journal Logo

Hoyt Lecture

More Than Meets the Eye: The Eye and Migraine—What You Need to Know

Digre, Kathleen B. MD

Author Information
Journal of Neuro-Ophthalmology: June 2018 - Volume 38 - Issue 2 - p 237-243
doi: 10.1097/WNO.0000000000000660
  • Free


The North American Neuro-Ophthalmology Society, in conjunction with the American Academy of Ophthalmology, established the annual Hoyt Lecture in 2001 in honor of William Fletcher Hoyt, MD, whose contributions to neuro-ophthalmology have spanned seven decades. A fellow of Frank Walsh, MD, the grandfather of clinical neuro-ophthalmology, Dr. Hoyt co-authored the 3rd edition of Clinical Neuro-Ophthalmology, the “bible” of our specialty. A faculty member of the departments of Ophthalmology, Neurology and Neurosurgery at the University of California San Francisco since 1958, Dr. Hoyt is world-renowned as a clinician, scholar and educator. He has published more than 300 scientific contributions and has trained more than 100 fellows, many of whom are senior professors in their own right, training the next generations of neuro-ophthalmologists on six continents.

I am deeply honored to give the 15th Hoyt lecture. The man we honor in this lecture, Dr. William F. Hoyt, was my academic grandfather; he trained both of my mentors—James J. Corbett and H. Stanley Thompson—with whom I trained at the University of Iowa. Dr. Hoyt left a huge legacy—not only the number of fellows he trained and the textbook he wrote, which for many years served as the definitive information source in neuro-ophthalmology, but also an entire optic disc collection that we include in the North American Neuro-ophthalmology Society (NANOS) Neuro-ophthalmology Virtual Education Library ( In his textbook, Hoyt recognized the prevalence of migraine, the many associated visual symptoms, and even mentioned the appearance of the cornea at the height of a migraine attack (1). Dr. Corbett also inspired my interest in migraine and headache when he and I would staff the Headache Clinic at the University of Iowa during my fellowship in neuro-ophthalmology. In addition, Dr. Thomson had me study the pupil in cluster headache patients. When I joined the faculty at the University of Utah, I started a headache clinic and restarted the neuro-ophthalmology clinic. So, you might say that for me, neuro-ophthalmology and migraine and headaches have been interwoven throughout my career. Although many of my colleagues in neuro-ophthalmology eschew migraine and headache, I hope that by connecting the 2 topics, I will at least spur better understanding between the 2 fields, and perhaps inspire neuro-ophthalmologists to embrace migraine and its various phenomena, as well as inspire headache specialists to appreciate how the eye and visual system help us understand migraine.

Approximately 18% of women and 6% of men suffer from migraine (2). This means that migraine is more common than asthma and diabetes mellitus combined, and it will be seen every day in patients who are being evaluated at ophthalmology, neurology, and neuro-ophthalmology clinics. Migraine has associated visual features such as aura and light sensitivity. It should not be surprising that there are even more features that intersect with vision, the visual system, and the eye. Although aura may only occur in about 1/3 of patients with migraine, photophobia or light sensitivity is an almost ubiquitous symptom during, and sometimes in between, an attack. Furthermore, 54% of patients when queried in a structured interview reported blurred vision with their migraine (3). Friedman and Evans (4) proposed that the blurred vision may be due to an imbalance in the sympathetic and parasympathetic systems—and may be related to tear film changes. Two facts connect migraine pain and ocular symptoms: first, trigeminal activation causes eye pain and second, autonomic dysfunction in either the sympathetic or parasympathetic pathway gives autonomic symptoms such as pupillary changes, lacrimation, redness to the eye and even blurred vision (5). It is really no wonder why migraine-related eye complaints are common in ophthalmology, neurology and neuro-ophthalmology offices.

Migraine is noted to be the second most disabling neurological condition next to stroke (6). For a disorder that affects vision, we wondered if migraine affected visual quality of life. In fact, when we were evaluating baseline quality of life measures in participants enrolled in the Idiopathic Intracranial Hypertension Treatment Trial (7), an astute reviewer asked: “How does migraine affect the visual quality of life?” Amazingly, that study had not been conducted. We used our headache clinic population to answer this question. We had patients with migraine complete the National Eye Institute (NEI) Visual Quality of Life instrument (VFQ-25) (8), the NEI Neuro-ophthalmic supplement (9), a migraine quality of life self-assessment (MSQ) (10,11), and the Headache Impact Test (HIT-6) (12,13). We found that chronic migraine affected the VFQ-25, Composite score to be 85 compared with controls at 96 (P < 0.001). NEI supplement score was 72 in chronic migraine and 95 in controls (P < 0.001); the MSQ scores compared with those obtained from controls were lower as expected. The higher the HIT-6 score was, the lower the VFQ-25 turned out to be, which was similar to the findings in the 11HTT (7). The subtests most involved included ocular pain. We found that the visual quality of life in chronic migraine affects the visual quality of life as much as Graves disease (14), IIH (7), and multiple sclerosis-associated optic neuritis (15).

Why would the eye be so important in migraine? To understand this, we need to understand: what is migraine? Migraine is believed to be an inherited disorder of sensory integration (16). The primary pain for this disorder comes from the trigeminal system, which includes the 3 branches of the peripheral cranial nerve; however, this system is more complicated than that—it also includes several trigeminal nuclei within the brainstem. The caudal nucleus of the trigeminal nerve (V) is an important relay station to the thalamus and then into the sensory system of the brain. The first division of the trigeminal nerve has rich arborizing branches to the eye and orbit. In fact, the cornea has the highest density of trigeminal nerve endings anywhere in the body (17). The first division of V, which supplies sensation to the eye and orbit, also supplies a large part of the dura (18). It has been postulated that dural afferents sensitive to peptides such as calcitonin gene-related peptide and other peptides are important in this migraine process (19). However, pain is only one part of migraine. There are prominent autonomic features in the migraine process, such as nausea and vomiting—and often prominent autonomic features during migraine and cluster headache that affect the eye: eyelid edema, pupillary changes, and tearing. Both the parasympathetic system by way of several nuclei such as the Edinger–Westphal nucleus, superior salivatory nucleus link to ganglia to the ciliary, facial, and lacrimal nerves. The sympathetic system has its headquarters in the hypothalamus and descends to the C8-T1 center, where after synapsing, it traverses up the carotid artery and enters the orbit through the first division of V to supply the pupil and lacrimal gland. These autonomic nerves also connect to blood vessels and regulate blood flow in the eye—with parasympathetic function often causing dilation and sympathetic function causing vasoconstriction. So, the proposed mechanisms of migraine, with its connection to the dura and autonomic elements, exactly parallels the innervation of the eye and orbital contents—it is NO surprise that the eye could be intimately involved in migraine (Fig. 1).

FIG. 1.:
The pathophysiology of migraine as a sensory processing disorder receives peripheral pain input from the dura and from the ocular sensory system—both by way of the first division of the trigeminal nerve. This, in turn, connects to the central trigeminal system including the nucleus caudalis. The autonomic system by way of the superior salivatory nucleus connects to both the dura and the eye through nerves emanating from the pterygopalatine (sphenopalatine) ganglia. These connections to the autonomic system affect blood vessels in the eye and dura and these autonomic connections cause many migraine symptoms such as nausea, tearing, pupillary changes, and others. Centrally, pain fibers ascend to connect to the thalamus, the amygdala, and the somatosensory cortices to give us conscious perception of pain, photophobia, and even an emotional aspect to migraine pain. The eye almost exactly mirrors the trigeminal input of the dura to the central structures and should, therefore, connect the eye into the pathophysiology of migraine. Reproduced with permission from (30).

By way of presentation of 4 cases, I hope that you will gain a greater understanding of these connections. The first patient is a 32-year-old woman who presents with eye pain. She asks her ophthalmologist for help. She has a history of migraine which used to be episodic but is now chronic (more than 15 days each month of migraine or migrainous features). Her eye examination is normal, but her Schirmer test result is 4 mm in each eye. Are these related?

Can tear film dysfunction (either dry eye or dry eye symptoms) be related to migraine? There are several clues in the literature. First, patients with classic dry eye associated with Sjögren disease have a higher prevalence of migraine—46% of patients have migraine (20). However, other studies have shown that you do not have to have Sjögren disease to have dry eye symptoms in migraine. Sarac et al (21) demonstrated that dry eyes and dry eye symptoms were more common in individuals with migraine than in normal controls, and that none of these individuals who were systematically studied had Sjögren disease. Although some studies (22) have shown that patients with migraine have lower Schirmer test results and tear film break-up time, many studies (22–26) have shown that the ocular symptoms of dry eyes are definitely increased in migraine. Shetty et al (25) found that even the optical properties of the tear film are abnormal in individuals with chronic migraine. Celikbilik and Adam (26) found that individuals with dry eye symptoms had longer duration of migraine attacks.

There are several clues as to why dry eye symptoms are increased in chronic migraine patients. First, the tear film is a balance between the trigeminal innervation to the eye (lacrimal gland along with the parasympathetic and sympathetic tone). Pflugfelder (27) has written extensively about the “integrated lacrimal functional unit.” The importance of the unit is that the trigeminal system and the parasympathetic/sympathetic systems are linked together. However, individuals may have more pain and normal or dysfunctional tear function. Migraine patients may have more trigeminal symptoms than nonmigraine patients related to the corneal nerve irritation. We have shown that patients with chronic migraine had excessive dry eye symptoms on questionnaires but normal basal tear secretion, corneal sensitivity, and results of Schirmer testing (28). Moreover, patients with chronic migraine exhibited decreased corneal nerve fiber density on confocal microscopy (28). A change in corneal nerve density also has been documented by Shetty et al (29). So, the corneal nerves may be abnormal in chronic migraine as a result of the migraine disease process, or the corneal nerve changes may be exacerbating the migraine disease process. Just as researchers have proposed that dural afferents play a role in migraine (19), so, too, the eye innervated by the same trigeminal system plays a role in the migraine process (Fig. 1).

We do not know if treatment of dry eye symptoms will improve migraine or not—but at least this is another level of understanding that we can add in taking care of our migraine patients, especially those with chronic migraine. Shetty et al (25) opined that treating dry eye symptoms may help with tear film aberrations and also may improve chronic migraine. In the patient described above, we treated her dry eye symptoms and her migraine, with improvement in her complaints.

Knowledge about migraine also helps the clinician when evaluating a patient with eye pain. The second case is a 30-year-old woman who had laser in situ keratomileusis (LASIK) surgery 6 months before we saw her. The procedure had gone well, but she returned with severe eye pain. She reported a “burning pain” (7 out of a 10-point pain scale) and worse when she used the computer. She had moderate photophobia and was using eye drops regularly. Her examination was normal except for a mild papillary reaction of the conjunctiva and very small punctate corneal erosions. She has a history of fibromyalgia and also migraines. She has some post-LASIK eye pain but we can learn more from her (30). Eye pain in the ophthalmology clinic usually divides between “red eye pain” due to conjunctivitis, dry eye, blepharitis, keratopathy, uveitis, iritis, foreign body, postsurgical, and scleritis/episcleritis. With “white eye pain,” we are thinking migraine, cluster headaches, optic neuritis, and idiopathic intracranial hypertension. We reviewed all the causes of eye pain in an ophthalmology clinic and a neurology clinic at 2 tertiary centers—University of Zurich and University of Utah (31). The most common causes of eye pain in the ophthalmology clinic were those “red eye pain” complaints: conjunctivitis, keratitis, dry eye, blepharitis, keratopathy; however, in the neurology clinic, migraine, optic neuritis, and cranial neuropathy were most common. You may find that asking about migraine will help you understand your patient's eye complaint. Although post-LASIK eye pain can be seen 6 months after LASIK in 20%–50% of patients (32), knowledge about the aforementioned anatomical structures involving migraine may hold true for persistent postoperative pain complaints of our patients.

We begin to see that migraine and eye pain can be a pain-processing problem. A recent study by Shtein et al (33) brings home this point. They compared patients with dry eyes to patients with fibromyalgia (a central pain processing problem) and normal controls (without any eye disease). They divided the dry eye patients into 2 groups: those with eyes that looked dry vs those whose eyes appeared normal. They found that the dry eye testing results with the Schirmer test were indeed lower in eyes that appeared dry, but dry eye symptom score was higher in those whose eyes did not look dry and who were similar to patients with fibromyalgia. They proposed that this was due to phenomenon of central sensitization (which we also see in migraine); this would account for patients who complained of dry eye symptoms but did not have dry eye signs (33). They also found that those patients with discordant dry eye scores (normal Schirmer test but abnormal dry eye scores) showed decreased corneal nerve density similar to what was seen in chronic migraine (28) as well as decreased visual quality of life. The decreased nerve density suggests that there is a neuropathic component to the pain which sets up peripheral sensitization (firing of peripheral nerves after an insult has occurred) and central sensitization where trigeminal neurons of the brainstem can fire independently. In migraine, central sensitization is believed to be a key factor in the migraine process leading to allodynia (34). The eye pain associated with dry eye symptoms could be another form of allodynia as a result of peripheral and/or central sensitization (35), and that just as allodynia may play a role in the chronicity of migraine (36), the dry eye symptoms may also play a similar role. This means that migraine as a sensory processing disorder also can involve the eye! In the case presented above, treating the cornea maximally with tears but also treating the patient's migraine with a preventative medication brought improvement of her complaints.

A third case shows us that patients with migraine have other visual symptoms—some related to the eye. A 17-year-old high school student presented with the chief complaint: “what is wrong with my vision?” He had a family history of migraine, and typical migraine with aura started when he was 9 years old. Typical migraines with aura occurred every 3–6 months. When questioned, he said he was experiencing several visual symptoms. First, he had “silvery lines” that were always present when he concentrated on them. He had floating and squiggly lines when he looked at the sky or snow. He stated he has had “grainy vision” all the time—as long as he can remember. These visual symptoms were NOT associated with any headache, and while he could see through these phenomena, they were very distracting. His entire examination is normal.

He was exhibiting the symptom of visual snow—a term that comes from analog television sets of the past when they were poorly tuned. Schankin et al (37) proposed several criteria for visual snow, including dynamic and continuous tiny dots in the visual field for at least 3 months. In addition, visual snow may include the presence of 2 additional visual symptoms: palinopsia (either trailing images or seeing the intact image when looking away), and enhanced entoptic phenomena (excessive floaters, “self-light of the eye” photopsias), photophobia, and nyctalopia. The symptoms are not typical of migraine aura and are not explained by another disorder (37). These symptoms are NOT migraine aura, which according to the International Classification of Headache Disorders 3 (38) is defined as a unilateral visual symptom gradually developing over 5–60 minutes and either followed by a headache (migraine with aura) or not (migraine aura without headache). It is not prolonged aura (an aura lasting over 60 minutes but less than 4 hours) (39); it is not persistent aura without infarction (38), which is a typical visual aura that lasts longer than a week with no imaging signs of infarction. It is not migraine aura status (38), which is a typical visual aura in a patient with migraine aura who experiences 2 aura episodes each day for at least 3 days.

Visual snow was described by Liu et al (40) as “persistent positive visual phenomena of migraine.” Visual snow is more commonly seen in individuals with migraine. About 60% of all patients with visual snow have migraine, but headache is a more ubiquitous complaint in almost 90% (37). The disorder is seen in both women and men and often is present in childhood (as in our case) in about 25% of cases. There is a high prevalence of tinnitus (63%). Other complaints include palinopsia 86%, floaters 81%, blue field entoptic phenomenon 79%, photopsias 63%, photophobia 74%, and nyctalopia 74% (37). Many of these symptoms, including floaters and blue field entoptic phenomenon, must come from the eye (retina, vitreous) (41); but, it also is recognized that visual snow is associated with a central processing problem—“noise” in the visual system (41). Positron emission tomography has shown hypermetabolism in the right and left lingual gyri (supplementary visual cortex), as well as in the cerebellum (42). Lauschke et al (43) called it a “thalamocortical dysrhythmia” due to dysfunctional neuronal excitability and impaired habituation response. Bou Ghannam and Pelak (44) called it a hyperexcitability of the primary visual cortex. Whatever the mechanism, visual snow is another example of a sensory integration problem seen with migraine (16)—integrating input along the visual pathway from the retina to the cortex.

Treatment of visual snow may be as simple as reassurance. Medications do not always work, but include lamotrigine, nortriptyline, carbamazepine, sertraline (45), and blue-yellow filters and FL-41 lens filters (43). We treated our patient with gentle reassurance that the phenomenon that he was experiencing was not aura but rather visual snow. We used migraine-specific treatments for his migraine.

Our final case is a 35-year-old woman with severe photophobia since a minor motor vehicle accident 6 months previously. She was no longer leaving her house due to her extreme photophobia. She did have a previous history of migraine, and her migraines had been somewhat more frequent (from 1 each month to 4–5 per month). She was wearing sunglasses in the office. Her visual and neurological examinations were normal.

Photophobia is a very common complaint (46). Many of the causes, including iritis, corneal abrasion, uveitis, and retinitis pigmentosa, will be readily diagnosed by an ophthalmic examination. Other causes such as blepharospasm, migraine, or posttraumatic brain injury may not be so obvious (47,48). Photophobia is a symptom worthy of an approach to a diagnosis. First, take a careful history and conduct a careful eye examination—look for dry eyes and corneal neuropathy. A drop of lidocaine eye drops can assist in making a diagnosis of a peripheral cause of photophobia. A complete eye examination will uncover ocular inflammatory or retinal disease. Then, look for blepharospasm—not all blepharospasm will be frequent blinking and squeezing, but can be “reflexive” to a light shine in the eye. Ask about migraine. Three simple questions can help you diagnose migraine. Are headaches disabling? Is there associated photophobia? Is there nausea and/or vomiting? If 2/3 of your questions are answered affirmatively, the predictive value is very high that this is migraine (49). If the patient complains of unilateral photophobia, also consider a trigeminal autonomic cephalagia (50). Of importance is that green light has been found to be the most tolerable light (51). When we examine patients with photophobia, we usually use the green light during ophthalmoscopy.

Photophobia also is a disorder of sensory processing. Whether it is processing input from rod/cones or the intrinsically photosensitive ganglion cells of the eye to the thalamus, these light sensors connect with dural/trigeminal pain afferents in the area of the posterior thalamus (52). Numerous studies have shown that the melanopsin pathway plays an active role in photophobia. Hattar et al (53) showed that mice with disruption of rods/cones but an intact melanopsin system were still light sensitive despite no formed vision, but those without melanopsin were light insensitive. Photophobia also involves disruption in the integration of the autonomic nervous system because pupillary light reflexes are altered in individuals with chronic migraine (54).

Why do we avoid seeing a patient wearing sunglasses in our waiting rooms? The “sunglass sign” may be an indicator of a psychogenic disorder (55). Is there an emotional component to photophobia? We studied this question in patients with migraine with interictal photophobia, migraine without interictal photophobia, and controls without migraine. We found depression and anxiety scores to be elevated in the patients with interictal photophobia (56). Animal studies have shown that emotional brain centers are involved in the process. Delwig et al found (57) that newborn mice (having only intrinsically photosensitive ganglion cells [melanopsin] at this stage) responded to light shone on them with vocalizations similar to distressed vocalizations when isolated from the litter. They also found that there was C-Fos expression in the posterior thalamus and light-induced activation in the amygdala (57). Recober et al (58) found that calcitonin gene-related peptide (CGRP) also was important in light sensitivity in mice. In fact, CGRP inhibitors reversed behavioral light aversion.

Treatment of photophobia requires a correct diagnosis. There are some principles to follow. First, reduce dark adaptation—those in the dark need to slowly come into the light. Treat underlying migraine, anxiety, and depression. Consider the use of tinted lenses. First described by Good et al (59) for prevention of migraine, FL41 tinted lenses have been studied in blepharospasm and migraine (60,61). All ophthalmologists should look carefully for dry eyes or dry eye symptoms and treat with lubrication, as well as with lid hygiene. Onabotulinum toxin has been reported to be helpful in the treatment of photophobia after head injury (62). Other treatments to consider include a sympathetic block, which has been shown to be helpful both in photophobia after a corneal injury (63) and in blepharospasm with severe photophobia (64). In our patient, we diagnosed that she had dry eyes and treated her with tears and lid hygiene, and we maximally treated her migraines with preventive medications. If she did not respond, we were considering treatment with onabotulinum toxin.

Migraine is a sensory processing disorder that involves the eye in many ways. Ophthalmologists, neurologists, and neuro-ophthalmologists need to know all about migraine—we will see it every day. We must realize that migraine is a factor in dry eyes, corneal neuropathy, and central sensitization after corneal surgery or injuries. We should be aware of symptoms of visual snow and correctly diagnose and treat our patients with photophobia. Ultimately, our efforts will lead to an improved quality of life for our patients with migraine.


The author would like to acknowledge her great neuro-ophthalmic partners Bradley Katz, Judith Warner, and Alison Crum; and her great headache partners Susan Baggaley, KC Brennan, Melissa Cortez, Karly Pippitt, and Christina Bokat, who collectively understand the importance of knowing neuro-ophthalmology and migraine phenomena. Also, the author would like to thank all the fellows he have had who have worked on projects related to migraine and the eye including Krista Kinard, Laura Hanson, Zubair Ahmed, Anastasia Neufeld, and Seniha Ozudogru. Finally, the author would like to thank the great medical students she has worked with in many of the studies mentioned above. And of course, the author would like to thank all of her patients that have taught her clinical headache and neuro-ophthalmology every day.

The author would like to thank Susan Schulman for her help in finalizing this manuscript.


1. Walsh FB, Hoyt WF. Clinical Neuro-Ophthalmology. Baltimore, MD: Williams & Wilkins, 1969:1654–1686.
2. Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol. 2010;30:107–119.
3. Queiroz LP, Friedman DI, Rapoport AM, Purdy RA. Characteristics of migraine visual aura in Southern Brazil and Northern USA. Cephalalgia. 2011;31:1652–1658.
4. Friedman DI, Evans RW. Are blurred vision and short-duration visual phenomena migraine aura symptoms? Headache. 2017;57:643–647.
5. Jacobson DM. Benign episodic unilateral mydriasis. Clinical characteristics. Ophthalmology. 1995;102:1623–1627.
6. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211–1259.
7. Digre KB, Bruce BB, McDermott MP, Galetta KM, Balcer LJ, Wall M. Quality of life in idiopathic intracranial hypertension at diagnosis: IIH Treatment Trial results. Neurology. 2015;84:2449–2456.
8. Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD. Development of the 25-item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol. 2001;119:1050–1058.
9. Raphael BA, Galetta KM, Jacobs DA, Markowitz CE, Liu GT, Nano-Schiavi ML, Galetta SL, Maguire MG, Mangione CM, Globe DR, Balcer LJ. Validation and test characteristics of a 10-item neuro-ophthalmic supplement to the NEI-VFQ-25. Am J Ophthalmol. 2006;142:1026–1035.
10. Jhingran P, Osterhaus JT, Miller DW, Lee JT, Kirchdoerfer L. Development and validation of the Migraine-Specific Quality of Life Questionnaire. Headache. 1998;38:295–302.
11. Bagley CL, Rendas-Baum R, Maglinte GA, Yang M, Varon SF, Lee J, Kosinski M. Validating Migraine-Specific Quality of Life Questionnaire v2.1 in episodic and chronic migraine. Headache. 2012;52:409–421.
12. Yang M, Rendas-Baum R, Varon SF, Kosinski M. Validation of the Headache Impact Test (HIT-6) across episodic and chronic migraine. Cephalalgia. 2011;31:357–367.
13. Rendas-Baum R, Yang M, Varon SF, Bloudek LM, DeGryse RE, Kosinski M. Validation of the Headache Impact Test (HIT-6) in patients with chronic migraine. Health Qual Life Outcomes. 2014;12:117.
14. Bradley EA, Sloan JA, Novotny PJ, Garrity JA, Woog JJ, West SK. Evaluation of the National Eye Institute visual function questionnaire in Graves' ophthalmopathy. Ophthalmology. 2006;113:1450–1454.
15. Mowry EM, Loguidice MJ, Daniels AB, Jacobs DA, Markowitz CE, Galetta SL, Nano-Schiavi ML, Cutter GR, Maguire MG, Balcer LJ. Vision related quality of life in multiple sclerosis: correlation with new measures of low and high contrast letter acuity. J Neurol Neurosurg Psychiatry. 2009;80:767–772.
16. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97:553–622.
17. Muller LJ, Vrensen GF, Pels L, Cardozo BN, Willekens B. Architecture of human corneal nerves. Invest Ophthalmol Vis Sci. 1997;38:985–994.
18. Feindel W, Penfield W, Mc Naughton F. The tentorial nerves and localization of intracranial pain in man. Neurology. 1960;10:555–563.
19. Goadsby PJ, Lipton RB, Ferrari MD. Migraine–current understanding and treatment. N Engl J Med. 2002;346:257–270.
20. Pal B, Gibson C, Passmore J, Griffiths ID, Dick WC. A study of headaches and migraine in Sjogren's syndrome and other rheumatic disorders. Ann Rheum Dis. 1989;48:312–316.
21. Sarac O, Kosekahya P, Yildiz Tasci Y, Keklikoglu HD, Deniz O, Erten S, Cagil N. The prevalence of dry eye and Sjogren syndrome in patients with migraine. Ocul Immunol Inflamm. 2017;25:370–375.
22. Koktekir BE, Celik G, Karalezli A, Kal A. Dry eyes and migraines: is there really a correlation? Cornea. 2012;31:1414–1416.
23. Yang S, Kim W, Kim HS, Na KS. Association between migraine and dry eye disease: a nationwide population-based study. Curr Eye Res. 2017;42:837–841.
24. Wong M, Dodd MM, Masiowski P, Sharma V. Tear osmolarity and subjective dry eye symptoms in migraine sufferers. Can J Ophthalmol. 2017;52:513–518.
25. Shetty R, Deshpande K, Jayadev C, Wadia K, Mehta P, Shroff R, Rao HL. The impact of dysfunctional tear films and optical aberrations on chronic migraine. Eye Vis (Lond). 2017;4:4.
26. Celikbilek A, Adam M. The relationship between dry eye and migraine. Acta Neurol Belg. 2015;115:329–333.
27. Pflugfelder SC. Tear dysfunction and the cornea: LXVIII Edward Jackson Memorial Lecture. Am J Ophthalmol. 2011;152:900–909.e901.
28. Kinard KI, Smith AG, Singleton JR, Lessard MK, Katz BJ, Warner JE, Crum AV, Mifflin MD, Brennan KC, Digre KB. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015;55:543–549.
29. Shetty R, Deshmukh R, Shroff R, Dedhiya C, Jayadev C. Subbasal nerve plexus changes in chronic migraine. Cornea. 2018;37:72–75.
30. Lee M, Digre K. A Case-Based Guide to Eye Pain: Perspectives From Ophthalmology and Neurology. New York, NY: Springer, 2018.
31. Bowen RC, Koeppel JN, Christensen CD, Snow KB, Ma J, Katz BJ, Krauss HR, Landau K, Warner JEA, Crum AV, Straumann D, Digre KB. The most common causes of eye pain at 2 tertiary ophthalmology and neurology clinics. J Neuroophthalmol. [published online ahead of print January 12, 2018] doi: 10.1097/WNO.0000000000000601.
32. Levitt AE, Galor A, Weiss JS, Felix ER, Martin ER, Patin DJ, Sarantopoulos KD, Levitt RC. Chronic dry eye symptoms after LASIK: parallels and lessons to be learned from other persistent post-operative pain disorders. Mol Pain. 2015;11:21.
33. Shtein RM, Harper DE, Pallazola V, Harte SE, Hussain M, Sugar A, Williams DA, Clauw DJ. Discordant dry eye disease (an American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc. 2016;114:T4.
34. Burstein R, Jakubowski M, Rauch SD. The science of migraine. J Vestib Res. 2011;21:305–314.
35. Crane AM, Feuer W, Felix ER, Levitt RC, McClellan AL, Sarantopoulos KD, Galor A. Evidence of central sensitisation in those with dry eye symptoms and neuropathic-like ocular pain complaints: incomplete response to topical anaesthesia and generalised heightened sensitivity to evoked pain. Br J Ophthalmol. 2017;101:1238–1243.
36. Louter MA, Bosker JE, van Oosterhout WP, van Zwet EW, Zitman FG, Ferrari MD, Terwindt GM. Cutaneous allodynia as a predictor of migraine chronification. Brain. 2013;136:3489–3496.
37. Schankin CJ, Maniyar FH, Digre KB, Goadsby PJ. “Visual snow”—a disorder distinct from persistent migraine aura. Brain. 2014;137:1419–1428.
38. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629–808.
39. Viana M, Afridi S. Migraine with prolonged aura: phenotype and treatment. Naunyn Schmiedebergs Arch Pharmacol. 2018;391:1–7.
40. Liu GT, Schatz NJ, Galetta SL, Volpe NJ, Skobieranda F, Kosmorsky GS. Persistent positive visual phenomena in migraine. Neurology. 1995;45:664–668.
41. Puledda F, Schankin C, Digre K, Goadsby PJ. Visual snow syndrome: what we know so far. Curr Opin Neurol. 2018;31:52–58.
42. Schankin CJ, Maniyar FH, Sprenger T, Chou DE, Eller M, Goadsby PJ. The relation between migraine, typical migraine aura and “visual snow.” Headache. 2014;54:957–966.
43. Lauschke JL, Plant GT, Fraser CL. Visual snow: a thalamocortical dysrhythmia of the visual pathway? J Clin Neurosci. 2016;28:123–127.
44. Bou Ghannam A, Pelak VS. Visual snow: a potential cortical hyperexcitability syndrome. Curr Treat Options Neurol. 2017;19:9.
45. Schankin CJ, Viana M, Goadsby PJ. Persistent and repetitive visual disturbances in migraine: a review. Headache. 2017;57:1–16.
46. Katz BJ, Digre KB. Diagnosis, pathophysiology, and treatment of photophobia. Surv Ophthalmol. 2016;61:466–477.
47. Digre KB, Brennan KC. Shedding light on photophobia. J Neuroophthalmol. 2012;32:68–81.
48. Truong JQ, Ciuffreda KJ, Han MH, Suchoff IB. Photosensitivity in mild traumatic brain injury (mTBI): a retrospective analysis. Brain Inj. 2014;28:1283–1287.
49. Lipton RB, Dodick D, Sadovsky R, Kolodner K, Endicott J, Hettiarachchi J, Harrison W. A self-administered screener for migraine in primary care: the ID Migraine validation study. Neurology. 2003;61:375–382.
50. Irimia P, Cittadini E, Paemeleire K, Cohen AS, Goadsby PJ. Unilateral photophobia or phonophobia in migraine compared with trigeminal autonomic cephalalgias. Cephalalgia. 2008;28:626–630.
51. Noseda R, Bernstein CA, Nir RR, Lee AJ, Fulton AB, Bertisch SM, Hovaguimian A, Cestari DM, Saavedra-Walker R, Borsook D, Doran BL, Buettner C, Burstein R. Migraine photophobia originating in cone-driven retinal pathways. Brain. 2016;139:1971–1986.
52. Noseda R, Kainz V, Jakubowski M, Gooley JJ, Saper CB, Digre K, Burstein R. A neural mechanism for exacerbation of headache by light. Nat Neurosci. 2010;13:239–245.
53. Hattar S, Lucas RJ, Mrosovsky N, Thompson S, Douglas RH, Hankins MW, Lem J, Biel M, Hofmann F, Foster RG, Yau KW. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature. 2003;424:76–81.
54. Cortez MM, Rea NA, Hunter LA, Digre KB, Brennan KC. Altered pupillary light response scales with disease severity in migrainous photophobia. Cephalalgia. 2017;37:801–811.
55. Trobe JD. Photophobia in anterior visual pathway disease. J Neuroophthalmol. 2002;22:1–2.
56. Llop SM, Frandsen JE, Digre KB, Katz BJ, Crum AV, Zhang C, Warner JE. Increased prevalence of depression and anxiety in patients with migraine and interictal photophobia. J Headache Pain. 2016;17:34.
57. 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:e43787.
58. Recober A, Kuburas A, Zhang Z, Wemmie JA, Anderson MG, Russo AF. Role of calcitonin gene-related peptide in light-aversive behavior: implications for migraine. J Neurosci. 2009;29:8798–8804.
59. Good PA, Taylor RH, Mortimer MJ. The use of tinted glasses in childhood migraine. Headache. 1991;31:533–536.
60. Blackburn MK, Lamb RD, Digre KB, Smith AG, Warner JE, McClane RW, Nandedkar SD, Langeberg WJ, Holubkov R, Katz BJ. FL-41 tint improves blink frequency, light sensitivity, and functional limitations in patients with benign essential blepharospasm. Ophthalmology. 2009;116:997–1001.
61. Hoggan RN, Subhash A, Blair S, Digre KB, Baggaley SK, Gordon J, Brennan KC, Warner JE, Crum AV, Katz BJ. Thin-film optical notch filter spectacle coatings for the treatment of migraine and photophobia. J Clin Neurosci. 2016;28:71–76.
62. Shoari M, Katz BJ. Treatment of the photo-oculodynia syndrome with botulinum toxin A. Neuroophthalmology. 2007;31:105–109.
63. Fine PG, Digre KB. A controlled trial of regional sympatholysis in the treatment of photo-oculodynia syndrome. J Neuroophthalmol. 1995;15:90–94.
64. McCann JD, Gauthier M, Morschbacher R, Goldberg RA, Anderson RL, Fine PG, Digre KB. A novel mechanism for benign essential blepharospasm. Ophthal Plast Reconstr Surg. 1999;15:384–389.
Copyright © 2018 by North American Neuro-Ophthalmology Society