MD Roundtable: Solving the Photophobia Puzzle

Clinical Update

NEURO-OPHTHALMOLOGY MD Roundtable: Solving the Photophobia Puzzle

moderated by leah levi, md with kathleen b. digre, md, and randy h. kardon, md, phd

his article is part of an occa- Research Target sional series of MD Round- tables, in which a group 1 of experts discuss a topic of interest in their field. ThisT month, Leah Levi, MD, of the Scripps Clinic, leads a roundtable on photophobia. She is joined by Kath- leen B. Digre, MD, of the University of Utah, and Randy H. Kardon, MD, PhD, of the University of Iowa. Fol- lowing are edited excerpts from their conversation.

Case Presentation Dr. Levi: I saw a 58-year-old woman yesterday who had a history of migraine with visual aura for about 3 years when she was in her 20s. That was followed by a long migraine-free The trigeminal nerve may be the link between dry eye symptoms and photophobia. interval until her early 50s, when she This image demonstrates the density of the trigeminal nerves in a cornea labeled began to get migraines 2 or 3 times a with antitubulin (a marker for nerves). year. About 5 years ago, the frequency of her migraines started to increase headaches. She has tried tinted glass- Defining Photophobia markedly, and they have remained es—and, in fact, had a brownish tint Dr. Levi: Help us understand photo- frequent since that time. on her glasses when I saw her yester- phobia. What is it? Challenging Symptoms. The day—and also tried a computer glare Dr. Digre: Photophobia is a misno- patient became increasingly light sen- screen. However, these have not helped mer, because photo means light and sitive to the point where she needed very much. phobia means fear. But it really isn’t a to wear dark glasses even in the house In addition, the patient has dry fear of light; it’s an unusual sensitiv- and would, when possible, stay in her eyes, but artificial tears haven’t helped ity to light. In other words, the light room with the curtains drawn. She was her light sensitivity even though they gives people a feeling of discomfort or put on amitriptyline, which allowed help the dry feeling. even pain. You need to differentiate it her to go outside, tolerate room lights, Finally, the patient has convergence from things like dazzle or hemeralo- and continue her job as a teacher. She insufficiencies, and her migraines are pia, because photophobia doesn’t cause was also treated with Botox and topi- also triggered by reading, but she’s people to have washout of their vision ramate, and they helped. However, she unable to do the computer-based con- or blindness. It causes discomfort— has remained intolerant of computer vergence insufficiency exercises at this and, in extreme cases like this one, it or other digital screens. These make point because she’s so light sensitive to triggers migraines and pain.

randy h. kardon, md, phd her photophobic and also trigger her the computer screen. Dr. Levi: Randy, can you talk about

eyenet 47 Neuro-Ophthalmology the connection between light sensitiv- patients complain of being more light Dr. Kardon: We have funding from ity and pain? averse under fluorescent lights that the U.S. Department of Defense to Emerging Research. Dr. Kardon: have a bluer component of light. try to develop an objective method This is an emerging area, both from of assessing light sensitivity. And by a neuroscience standpoint and from Individual Responses light sensitivity, I mean not only the putting this together with patients’ Dr. Levi: What factors seem to influ- amount of light reacted upon by the complaints. The pathways in the brain ence the individual variations in light retina but also the trigeminal system that are stimulated by light are still be- sensitivity? and the brain’s response to the light. ing elucidated. Some of the evidence Dr. Digre: All of us have a threshold Exaggerated Response. Of shows that light-conducting nerves for light sensitivity. If you go into a course, the amount of light getting from the eye have input to the thala- movie theater in the middle of the af- to the input side of the equation can mus. The nerves modulate pain fibers ternoon and you come out into bright be monitored by the pupil reaction to that are coming to the thalamus from sunlight, your first response is to close light. But if you look at patients who the meninges lining the brain. This your eyes or squint. But it’s clear from have an adverse, painful response to pain signal is also conveyed to the sen- studies that people with migraine and light, their pupil responses aren’t ab- sory trigeminal nucleus in the lower blepharospasm have lower light sen- normal compared with age-matched brainstem. These “way stations” that sitivity thresholds than normal, and subjects who don’t have this reac- translate light into pain are still not that’s probably part of the pathophysi- tion to light. So, most cases of light completely elucidated. It’s important ology of these conditions. sensitivity cannot be explained by an to try to understand them, because Dr. Kardon: One aspect to consider increase in sensitivity of the retina to knowing the pathways and knowing is whether more light is getting to the light. Rather, the signal from the retina the neurotransmitters leads the way to- retina or whether the patient’s reac- is being acted upon in an exaggerated ward new therapeutic interventions. tion to the light is exaggerated. For way by the recipient areas of the brain. CGRP and the Trigeminal Nerve. example, some of the work we’ve pub- Exceptions to this are patients who For example, a major neurotransmit- lished shows that in patients with blue do have exaggerated sensitivity of the ter that modulates pain is calcitonin irides lacking melanin pigment, a lot of retina to light—for example, patients gene–related peptide (CGRP). Differ- light goes right through the eye to the with achromatopsia. ent pharmaceutical companies have retina in spite of the pupil’s size. So, How can one measure an exagger- been trying to develop new drugs that even if these patients have their pupils ated sensitivity of brain areas receiving modulate the CGRP response for treat- constricted with a cholinergic agent to the retinal light signal? One good can- ment of migraines, and these drugs make them miotic, plenty of light still didate would be recording the degree may have an impact on the effect of gets through to the back of the eye. of a photic blink reflex. The photic light on pain. The trigeminal nerve, The extreme of that, of course, would blink reflex has some similarities to which has CGRP as its neurotransmit- be albinotic patients who are extremely the corneal blink reflex: If something ter, innervates the cornea, the orbital light sensitive no matter what size touches the corneal nerves, it initiates structures, and the lining of the brain. pupil they have. So, it is important to an input to the trigeminal sensory Once one part of the trigeminal nerve keep in mind that the pupil and the nucleus in the brain stem that causes becomes activated and sensitized to an eyelids may not be efficient at limit- the facial nerve to fire, and the person inciting stimulus, then other divisions ing the light getting into the retina in blinks. Similarly, if a bright light is may also become sensitized, resulting lightly pigmented patients. shined into the eye, the photic blink in different patterns of referred pain to Dr. Levi: That’s an interesting point, reflex causes the eye to blink, provid- the eye, orbit, or head. because I’ve had patients who have just ing a protective mechanism. We’ve That’s why in your patient, for ex- a general complaint that they’re getting been trying to take advantage of this ample, dry eye that may be influenc- more light sensitive as they age, and objective blink reflex by recording the ing the trigeminal nerve may in turn they don’t have any underlying pathol- electrical responses around the orbicu- adversely increase the sensitivity to ogy—and most of those patients, if not laris and procerus muscles in response other stimuli such as light and even a all of them, have blue irides. to light. We found that it’s a graduated, particular wavelength of light (Fig. 1). involuntary response—the more light Certain neurons that contain mela- Measuring Photophobia stimulus you give, the greater the acti- nopsin in the structures of the eye may Dr. Levi: One of the frustrating things vation of those muscles. be more sensitive to blue wavelengths. about photophobia is that it seems to Involuntary Muscle Contraction. This might explain why some patients be such a subjective complaint. Is there Patients who are migraineurs and who achieve some relief of their light sensi- any way of measuring this that either complain of light sensitivity have an tivity by wearing eyeglasses that have of you know about or are developing? exaggerated electrical response and an orange tint that blocks the blue If so, is it going to find its way eventu- contraction of the muscles around component of light. Many of these ally into the office? their orbicularis and procerus and

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brow muscles compared with patients uveitis. And then even in the posterior 2 who are not. We’re also trying to segment, people who have albinism— monitor this response from a video re- or some of the achromatopsias, cone cording; the amount of contraction of dystrophies, or retinitis pigmentosa— the eye muscles and the brow muscles are extremely light sensitive. can be quantified without an electrode Impact of Surgery. Dr. Levi: What using facial features extracted from about factors such as contact lens use videos. We’re trying to quantify this or LASIK? involuntary activation of the facial Dr. Digre: I’ve certainly seen many muscles in response to different doses people who’ve had LASIK or cataract of light to give an objective measure surgery or some other surgical pro- of light responsiveness that might in- cedure become more light sensitive. dicate which patients are abnormally Again, sometimes it starts out with a Reflexive blepharospasm is a common light sensitive—and, furthermore, dry eye complaint—but treating the nonocular condition associated with which agents or mitigations might re- dry eyes, as you did in your patient, of photophobia. verse the exaggerated response to light. does not seem to ameliorate their light Dr. Digre: I would like to point out sensitivity. migraine, like your patient, and turn that as people age, their blink reflex Dr. Kardon: Some of the emerging them into a chronic migraineur? Or is becomes shorter. Babies, for example, science behind this is that there are the migraine process actually produc- can stare at lights for long periods different sensory channels in the tri- ing changes in the corneal nerves? of time without blinking, but older geminal nerves that innervate the cor- I think Randy’s point about what people, even normal older people, will nea, and they have different functions. we’re learning about the cornea is blink more readily. Some sense temperature. Some sense extremely important. We need much Examination Aids. Dr. Digre: I’d acid content. Some are multimodal more science on the nerves that inner- also like to say that there are question- channels. Some sense just mechanical vate the cornea as well as these chan- naires for photophobia. Not everybody touch. And some of these channels— nels. The nerve factors, growth factors, has a machine to test for light sensitiv- and the nerve transmitters in the nerve and transmitters are going to turn out ity, but validated questionnaires are that mediates them—probably become to be very important. And so I think available in the literature. disturbed after some of the corneal there is something like corneal neu- Dr. Kardon: I’d like to amplify on procedures, and they give the feeling of ropathy. These are people whose cor- that. One interesting thing is that most dry eye even though, for example, the neal nerves are not normal. They have of these patients don’t really complain eye may be producing tears. atypical corneal sensation, and they that the light seems brighter than Further research will elucidate how tend to have really bad photophobia. normal. Most of the time, they’re com- the sensory channels in the cornea plaining that a certain brightness of modulate light sensitivity and ab- Nonocular Causes light is causing them to feel pain, and normal trigeminal activation during Dr. Levi: For most ophthalmologists, the questionnaires that Kathleen men- transduction of the signals. Future the most frustrating patient is the one tioned try to capture some of that. It’s investigations will focus on how to test who’s complaining of photophobia not just that the patient reports that these corneal sensory channels: How but has a completely normal ophthal- the light is brighter, it’s that the patient do you determine if they’re abnormal, mological examination. What are the has an adverse response to a normal and how can you restore the normal most common nonocular conditions brightness of light. sensory function of corneal channels? associated with photophobia? Corneal Neuropathy. Dr. Levi: Migraine and Blepharospasm. Ocular Causes Kathleen, there’s a concept called cor- Dr. Digre: The first and most common Dr. Levi: What are the most common neal neuropathy that’s been presented neurologic disorder is migraine. It ocular causes that lead to photophobia? by Perry Rosenthal in Boston. Can you affects 20% of all women, 10% of all Dr. Digre: I think the number-one make a few comments about that in men. As with the patient presented in thing is dry eyes or dry eye symptoms. light of Randy’s comments? your case study, photophobia patients This can occur as people get older, Dr. Digre: Well, we have looked often have a history of migraine, and it as in your patient. Previous corneal at corneal nerves in people who have tells you something about their brain injuries or inflammation may change chronic migraine, for example, and and the way they process pain that the corneal nerve structure and lead to there’s some indication that there may can set them up for things like chronic more light sensitivity and photophobia be some changes in the corneal nerves. photophobia. or pain with light. Photophobia also But what’s the chicken and what’s the The second one is blepharospasm. can occur with any kind of inflamma- egg? Are the corneal nerves abnor- Blepharospasm is not just sitting there

eyenet 49 Neuro-Ophthalmology are different types of blepharospasm. an aversion to light—or is headache a fice or anything like that. They were Some are just reflexive blepharospasm major component of this?” Most of the light sensitive all the time. —in other words, the patient is reflex- time, headache is a major component Dr. Kardon: I would echo that. Be- ive to bright light and can be in normal to the light sensitivity. sides light sensitivity, migraineurs, light and not have a problem, but as Dr. Digre: And it may not just be a between episodes, seem to be more soon as the bright light hits them, they headache. It could be eye pain as well. sensitive to other modalities of stimu- go into blepharospasm attacks (Fig. 2). And neck pain, because the trigeminal lation. Referring back to your patient Other neurologic conditions should system also serves some portions pos- with regard to how sensitive she was be considered. For example, pituitary teriorly—so there could be eye pain to computer screens, it was probably tumors can present with the chief and neck pain as well as whole head movement. Responses to different complaint of photophobia. Progres- pain. types of sensory stimulation and dif- sive supranuclear palsy, a kind of Par- Dr. Kardon: I agree with that com- ferent types of visual stimulation com- kinsonism, has been associated with pletely. monly seem to be overexaggerated in photophobia. Meningitis—anything More on Pituitary Tumors. Dr. migraineurs, even when they’re not that affects the meninges—can cause Levi: Kathleen, just to elaborate on the having a migraine. photophobia. Even medications have point you made that some people with More on Computer Use. Dr. Levi: been associated with photophobia. pituitary tumors can be light sensitive. What is it about computer screens? Traumatic Brain Injury. Dr. Kar- I presume that those patients would This is such a common complaint. I don: One of the common emerging have some compression of the chiasm certainly hear in my practice about causes that we’re seeing, both in the or the optic nerves that might show up how patients can do everything else, veteran population and in sports, is on another examination such as a vi- but the computer screen or some other that traumatic brain injury and con- sual field (VF) test that can be done in screen or fluorescent lighting really cussions also seem to trigger light sen- the office. bothers them. sitivity. In veterans who have returned Dr. Digre: You could do a VF, but it’s Dr. Digre: Well, fluorescent lights from recent battle, about 59% report probably the stretch of the dural sheath and some computer screens have a light sensitivity. And the brain injury around the pituitary—again, the dura little oscillation and movement. As often causes a migraine-like headache and the meninges of the brain are in- Randy said, this movement—any in addition. And so we have a mixture nervated by the trigeminal system. So movement in the periphery—is a great of light sensitivity and headache that getting a VF is a good first start. Then, trigger for developing a migraine. worsened after traumatic brain injury. maybe asking—both women and These people just are extremely sen- It’s not uncommon for people to show men—about galactorrhea or changes sitive to all sensory input and move- up in the waiting room wearing very in ring size and hat size; those might be ment and contrast. Heavily contrasted dark sunglasses who are disabled and reasonable to do in the office. or figured items—stripes or checker- who’ve had a history of concussion and More on Migraines. Dr. Levi: Can boards or anything with contrast and traumatic brain injury. you talk about photophobia in patients pattern—can really trigger migraines Dr. Levi: A lot of patients are in mo- with migraine even when they’re not in certain susceptible people. ■ tor vehicle accidents, for example, and having a headache? A lot of them seem are rear-ended and have whiplash, and to just be generally more light sensitive Dr. Digre is professor of ophthalmology and that’s followed by various headaches than the rest of us. visual sciences and neurology at the John A. and photosensitivity. In my practice, Dr. Digre: That’s been shown in Moran Eye Center at the University of Utah in that’s a common scenario as well. numerous studies. For the experience Salt Lake City. Relevant financial disclosures: Complexity of Pain. Dr. Levi: of migraine headache, one of the key None. Many patients who’ve had a concus- components is photophobia; 90% or Dr. Kardon is professor of ophthalmology and sion and who complain of photosen- more of people with a migraine will visual sciences and director of the Neuro-oph- sitivity also have a migraine history. have photophobia. Sound sensitivity is thalmology Service at the University of Iowa Randy, do you see patients who have another question to ask that points to in Iowa City. Relevant financial disclosures: no migraine history but then do have migraine. Nausea, also, can go along Department of Defense TATRC: S; MedFace: photophobia after concussions or trau- with migraine. But even between mi- O; National Eye Institute: S; Novartis: C; Vet- matic brain injuries? graine attacks, these individuals have erans Health Administration: S. Dr. Kardon: Almost all of these cases been shown to be more light sensitive. Dr. Levi is director of ophthalmology at seem to be associated with headache In fact, one study was done just ask- Scripps Clinic in La Jolla, Calif. Relevant fi- and migraine-like symptoms, in my ing people, “Are you light sensitive all nancial disclosures: None. experience. The light triggers head- the time?” If they answered “Yes,” it See the disclosure key, page 8. ache, so an important question to ask was very predictive of them having is, “Are you light sensitive but have underlying migraine, even though they NEXT MONTH: Photophobia Roundtable, no headache from it, and you just feel weren’t wearing dark glasses in the of- Part 2: Diagnosis and Treatment.

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