Transcript of Cyberseminar
Mild TBI Diagnosis and Management Strategies
Photosensitivity after Traumatic Brain Injury (TBI): Mechanism, Diagnosis and Treatment
Presenter: Randy Kardon, MD, PhD
October 10, 2013
Moderator: And we are now at the top of the hour. So I am just going to double check real quick. Dr. Depalma, do I have you on the call. Okay, I do not see him in the meeting. Generally, we have the series organizer present the speaker. But Dr. Depalma is not in the meeting currently. So I will take the pleasure of introducing Dr. Randy Kardon. He is a professor and director of neuro-ophthalmology, also director of Iowa City VA Center for Prevention and Treatment of Vision Loss and Pomerantz Family Chair of Ophthalmology in the Department of Ophthalmology and Visual Sciences. So at this time, I would like to turn it over to you Randy.
Dr. Randy Kardon: Thank you. Thank you all for joining in today. One of the reasons I wanted to give a webinar on this topic is that many of you out there are seeing patients that have photosensitivity of different causes and because this seems to be appearing more in patients after traumatic brain injury. We are seeing more of these patients especially in the VA system. And many people who try to treat these patients are frustrated. And the patients are frustrated. And many of these patients are sometimes referred for psychological or psychiatric evaluation because there does not seem to be anything wrong on their examination. Yet they are suffering from light sensitivity that is very debilitating. And many people want to run in the opposite direction when these see these patients because they are sitting in the waiting room with sunglasses on and it is very frustrating.
So I thought I would try to bring some of the science to there and this topic today and also our clinical experience and what we are doing to try to objectively determine whether patients have photosensitivity. And how we might use this to monitor new treatments, which I will share with you today.
Moderator: Randy, I apologize for interrupting. Can I ask you to please increase the volume on your telephone or speak a little louder? It is coming through quite softly. Thank you.
Dr. Randy Kardon: How is that?
Moderator: That is a little bit better thanks.
Dr. Randy Kardon: Okay. I did want to disclose any financial interests I have. These come in the form of funding from the National Eye Institute and also funding from the Department of Defense and funding from the VA Rehabilitation Research and Development. I also serve on steering committee for Novartis for monitoring MS using optical coherence tomography of the retina. And I serve on the steering committee for Acorda advising them about visual symptoms in MS. And I also give advice to Zeiss Meditec on better ways of doing perimetry and optical coherence tomography. None of these should have any impact on what I am going to tell you today.
I wanted to first start out with a poll question just to give us an idea of what your role is in the VA. So if you could please check whichever one applies to you. The last choice is other if we did not categorize every single person who is out there.
Moderator: Thank you very much. We do have the answers streaming in. So thank you to our attendees for responding to this poll question. It does help give us an idea of who is in our audience and who best to direct this towards. So your options are ophthalmologist, optometrist, neurologist, primary care physician or physician’s assistant, occupational/physical therapist, social worker, research scientist, or other. And it looks like the results have stopped streaming in. Do you want to review those real quick?
Dr. Randy Kardon: So it looks like about 28 percent are optometrists, about 2 of you out there are neurologists, 2 are primary care or physician’s assistants, 5 are occupational therapists, 7 are in the field of social work, 4 are research scientists, and 31 are in the other category.
Moderator: Thank you.
Dr. Randy Kardon: Second poll question just out of interest is how many new patients with photosensitivity do each of you see in a year? And the choices are 1 -5 patients a year, 6 – 10 patients a year, 11 – 20 patients a year, or over 20 patients. And I guess if you do not see any, you could put in no vote.
So it looks like the great majority about over 70 percent sees more than 20 patients a year. About 11 percent see 11 – 20 patients. And 10 percent see about 6 – 10 patients. And about 8 percent see 1 – 5 patients. So most of the audience seems like you are seeing some of these patients in your different venues with the VA. Thank you.
Anyone who deals with the patients with photosensitivity recognizes that there is not just one cause. And I want to just briefly review the known causes of the patients that do come in with photosensitivity. There are patients who just come in with an eye problem with acute uveitis, which is commonly associated with photosensitivity. These patients usually do not have any other causes. Patients with retinal dystrophies, particularly cone dystrophies and there are some other rare dystrophies often have photosensitivity. And the reasons for this are not entirely known. Patients who have had a previous meningitis and after the meningitis clears, there is often an effect of photosensitivity that is long lasting that usually never goes away.
There are some brain tumors that present with photosensitivity. These are sometimes thalamic tumors such as thalamic gliomas. And there are a few patients reported with pituitary tumors, benign pituitary tumors that have photosensitivity.
The great majority of patients at this point in time are patients who have a history of migraines. And I do not mean just patients who have photosensitivity during their migraine, which is very common as well as sound sensitivity. But many migraine patients are left with photosensitivity even when they are not having a headache. It is a very common complaint. And the other common complaint is the recent self-reported survey shows that after traumatic brain injury in the military, about 59 percent report that as a common symptom. So that is one of the reasons, I think, many of you out there are seeing more of this in the last few years. Because it is the most common visual symptom reported in traumatic brain injury whether it is mild, moderate, or severe.
Some people have questioned whether there is a psychogenic component. I think that is still on the table. There might be psychological factors that may influence it. But I do not think there is much evidence that is purely just psychogenic in nature.
I wanted to review some of the literature that brings to bare some of what is the current thinking about light sensitivity. And I wanted to preface this by saying that most of this falls into two categories in terms of clinical patients. Those that perceive the light as being brighter, but they do not really have a headache or pain component. And that would be usually in the minority. The great majority have more of a pain component that is exacerbated by light, pain either around their eyes or headache. And many patients, as I mentioned, are known migraineurs and it may induce a migraine headache when they see light. So you should keep this in mind when you are questioning a patient which of the two they fall in to.
The reason this is important is some current thinking is that patients with increased perception of brightness may be caused by a retinal or a visual cortical abnormality. But patients who have pain, actual discomfort and pain with photosensitivity are more likely to be having something that involves the thalamus and the trigeminal system of the brain.
This is one paper that was interesting because it brought together information from both patients and also from animal models. And this was out of Harvard. And Dr. Rami Burstein is a headache specialist at Harvard and also deals with a lot of photosensitivity. And I am going to show some summary diagrams. And in a nutshell, what this study found is first that there are patients that have loss of photoreceptors. They do not have any functioning rods and cones that also have photosensitivity. So this was a paper that highlighted the fact that you do not need rods and cones to be photosensitive. And the second important aspect in the animal model is they showed that the neurons conveying a light signal from the eye, the ganglion cells that contain the photopigment, melanopsin, a relatively new class of retinal ganglion cells that have been discovered in the last 10 – 12 years. These melanopsin containing retinal ganglion cells that can be directly activated by light, they feed into areas of the thalamus that modulate pain sensitivity that is converging onto the thalamus from the meninges and from other pain sensitive areas of the brain including the peripheral trigeminal nerve.
This is a diagrammatic view of this. And what you are seeing here is that in the eye diagram in the upper left hand corner of your screen, there are these intrinsically photosensitive retinal ganglion cells that are labeled red that convey their input from light directly into the optic nerve. And most of these either project to the areas of the brain in the hypothalamus that set the circadian rhythm. They also project to the pupil centers of the brain. So they are the main nerve that conveys our pupillary light reflex, the after arms of the brain. But they also project to the thalamus. And it was in this area of the thalamus where they actually did recording of nerves there. It showed when you record from nerves in the thalamus, the recording of the thalamic nerves that convey pain sensation, the firing increased dramatically when light was shined into the animal’s eye. And they also seemed to be the weight station conveying pain input from the, as I mentioned, the meningeal nociceptors shown in the left hand portion in blue. And these are conveyed by trigeminal neurons to the thalamus.
So it is thought that the thalamus is acting somewhat as a weigh center for the pain. And input from the optic nerve via these melanopsin containing retinal ganglion cells in the animal model was recording seems to modulate this response dramatically. So here is a physiologic basis for how input from the eye can modulate pain and headache that is commonly seen in these patients.
Right now, there is not any anatomical evidence that the input from the melanopsin containing retinal ganglion cells projects directly to the spinal area of the sensory nucleus and the trigeminal nerve in the lower brain stem. But this is also a possibility. Right now, most of the evidence is this is conveyed directly to the thalamus, which is also connected by nerves to the sensory trigeminal nucleus in the lower brain stem.
Another important concept in the area of migraine photosensitivity is that one of the main neurotransmitters in both animals and in humans is the neuropeptide called calcitonin gene-related peptide, abbreviated CGRP. And this is a neurotransmitter that mainly modulates trigeminal activity in the eye and the brain. So this is a major neurotransmitter found in the trigeminal sensory system that senses pain. And it has been found in a number of papers that this neuropeptide level goes up during a migraine attack. And also, if you inject this substance under the skin, for example, in migraineurs, it will induce headache and photophobia. And there are receptors for this calcitonin gene-related peptide in different areas of the brain. But they are highly concentrated in the trigeminal sensory nucleus in the brainstem, which is one of the weigh stations for the brain.
So there is mounting evidence that this is a neurotransmitter who has a receptor. And both of these play a key role in not only headache and migraine, but probably also in photosensitivity. The reason this is important, which I will touch on at the end of the talk, is that some of the new drugs being developed to treat migraine that are not yet approved for use that are in clinical trials are antagonists to CGRP. And so while these drugs may relieve migraine or prevent migraine, they may also have a similar effect on light sensitivity. So I wanted just to give the audience the information that there are new drugs that are being developed that might have a large therapeutic impact on these patients that are debilitated by light sensitivity.
This is just a screenshot from another interesting paper on the mechanisms of photophobia. And what is interesting about this study, it does not look like it is coming through very well on the Power Point. Maybe you can see it better. Is that bright light increases a trigeminal mediated blink reflex. So whenever we blink, if someone touches our cornea or if you feel something in your cornea that is a brainstem reflex. But there is also a reflex to light that causes us to blink. And this can be measured in humans and in rodents. And light can modify this reflex through a system in the brain.
This is also an important paper in an animal study that showed that bright light activates the trigeminal system. And this was not previously understood how this might happen. I am going to show a diagram on the next slide that outlines what the studied showed. And in a nutshell, it showed that it appears as though light activates nerves in this trigeminal sensory nucleus in the brainstem. And what is interesting about it is that the paper addresses how does the light actually get to stimulate the trigeminal system. And what the paper showed is that there appear to be some mechanisms by which light actually makes the blood vessels in the choroid, the vascular layer in the back of the eye that supplies much of the photoreceptors. It causes these vessels to dilate and stretches trigeminal nerves that supply the blood vessels that might stimulate the trigeminal nerves.