Lecture: Optic Neuropathy, Part I

This webinar will cover presenting symptoms and signs of inflammatory, demyelinating and selected infectious optic neuropathies. Specific entities will include “typical” idiopathic optic neuritis, multiple sclerosis, neuromyelitis optic spectrum disorder, anti-MOG, sarcoidoisis, CRION, Bartonella henselae, syphilis, and tuberculosis.

Lecturer: Dr. Karl Golnik


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DR. KARL GOLNIK: This is our third neuro-ophthalmology Orbis webinar. We’ve covered pupils and visual fields, and now we’re moving on to optic neuropathies. I think this will be probably no more than two parts, but I don’t think we can cover all of optic neuropathy in one hour. So the next neuro-ophthalmology will be a continuation of this, and we’ll cover other entities I’ll mention when we’re done with the webinar. So my objectives for the webinar are that, when we’re done, you’ll be able to describe how to diagnose an optic neuropathy, and also be able to list the differential diagnosis of inflammatory optic neuropathy. I’m gonna start with a little prelecture test. I’m gonna show you a few optic discs. They’re all individuals who present with unilateral visual loss, noted over just a few days. So fairly sudden or subacute. And then the question, when you look at the nerves — just by looking at the nerves — is the evaluation the same for each patient? Or is it different, depending on the optic disc appearance? So let’s look at nerve number one. You can see here a nerve that’s rather swollen. There’s some hemorrhage. So a very swollen optic disc with hemorrhage. Nerve and fundus number two, a swollen nerve — you can see there’s a little hemorrhage as well inferiorly, plus this macular star of exudate. And nerve number three, which really looks very normal, and in fact, when we looked at the other nerve, it looked just like this one. So this nerve is completely normal. So the question is — and we’ll get to this at the end — is there a difference as to how these patients are evaluated? So here’s my first polling slide, and I’m gonna see if I can remember how to do this. Polling… Okay. So the question is… Most optic neuropathies in young adults are caused by which of the following four things? And I’m gonna launch the poll. So you can now vote. And this is sort of a question that depends upon, I think, perhaps, on where you live. We’ll make that point. Are they usually — when you see optic neuropathy in young adults — I guess we need to define young adults. I used to define it based on anyone my age and younger. I can’t do that anymore. So let’s say under 50 years of age I’m gonna call young. Sorry for everyone else who’s over 50. Is it usually inflammatory, infectious, ischemic, or compressive? And I’m gonna give a minute or two — I’m watching the votes roll in. I have about half the people have voted who are on the webinar at this point. So I’ll give everybody about 10 more seconds. There’s not necessarily a correct answer to this. It depends, I think, on what you see. So I’m kind of doing this in part for my benefit, to see what everyone is seeing out there. And I’m gonna give you 5 seconds. 4, 3, 2, 1. And share the results. And hopefully you’ll be able to see the results. Not unexpectedly, about 74% or 3 in 4 say inflammatory. And then most of the rest of you it’s infectious. And clearly this is also my experience. Inflammation and infection definitely the most common in young adults. You see a rare ischemic optic neuropathy and compressive optic neuropathy, and indeed, those are two of the topics we’ll be talking about in our next webinar. And I’m gonna move on. Good. So what about the history? Let’s talk briefly about that. So the history is important. I want to know: When did the visual loss start? Was it yesterday? A week ago? Or has it been going on gradually for months? So in patients with inflammatory or infectious optic neuropathies, typically it’s gonna be acute or subacute, whereas in patients like seen in our MRI in the middle here, with a compressive lesion, with that tumor in the back of the eye, compressing the optic nerve, this was a patient who had a very slow, progressive course. So you’re probably not gonna be thinking about inflammation or infection, whereas this patient in the upper left has an enhancing optic nerve, characteristic of optic neuritis. What about pain? So some optic neuropathies are painless and some are painful. Again, usually inflammatory and infectious processes tend to be painful. They don’t have to be. It doesn’t have to be severe pain. In the patient on the upper left, they’ve got a little bit of enhancement back here at the optic chiasm, and that may well be painless, even though this is inflammation. Most patients with inflammatory or infectious optic neuropathy have some sort of discomfort. But even people with big tumors like you’re seeing on the MRI in the center — they usually don’t have pain. Probably because they’re slowly progressive. But people are often surprised when I let them know that they have a tumor. They say — gee, I don’t have any pain. How can that be? Most tumors are painless. What about — is it an isolated eye problem? Or is it systemic? So one of my questions I always ask patients, almost about any visual problem, is: Is this isolated to your vision or to your eye? Is there anything else going on? Arms, legs, et cetera? In patients with some of the conditions we’ll talk about, there are often other systemic problems or symptoms, and this MRI is showing some lesions in the spinal cord. We’ll see this MRI again, I believe, later on, when we talk about specific entities. In the center photo, you see someone with optic disc drusen, which is gonna be typically a very isolated ocular visual-type problem. How about past medical history? Well, certainly in people who have significant past medical histories of thyroid, and this patient in the upper left has large extraocular muscles, and you can see how this optic nerve is being compressed between the extraocular muscles, and not surprisingly, has optic neuropathy. The patient in the photo illustrated in the middle here — we see an optic nerve that’s been infiltrated in a patient with leukemia. So anybody with a history of thyroid or cancer — obviously you have to consider these entities in the differential diagnosis of their optic neuropathy. Family history, of course, can be important. We’ll talk about that again in our next webinar. But patients with optic disc drusen, that can run in the family. And in this patient, you don’t see any obvious drusen in the photo on the left. There’s a little bit of concentric hemorrhage here, which is something I can commonly — well, not commonly — something I can see with optic disc drusen. And when I see a nerve that looks a little swollen like this, and a little concentric hemorrhage, usually there are buried optic disc drusen, and you need ultrasonography to diagnose that. We’ll cover that in the next webinar. In the patient in the middle here, the nerve looks slightly swollen. It’s actually pseudoswelling in a patient with Leber’s hereditary optic neuropathy. Social history is important. Where have they traveled? Do you have cats? Things like that. In the United States, not often — probably in a lot of other countries — we’ve had this picture of neuroretinitis, a star of exudate with a swollen disc. In the United States, this is usually cat scratch disease. And Lyme is — we see Lyme disease as well in the US, but the point of this map is that, depending on where you live in the US, most people in the US aren’t exposed to Lyme. But if you live in New England, up here, there’s a high prevalence of Lyme, and in the upper Midwest as well. But if you live elsewhere — and I live right about down here — I rarely ever see Lyme. If you live up here in New England, you’re gonna see it frequently. And similarly, here’s a map of the incidence of tuberculosis by country. So depending on where you live, you may see lots of tuberculous optic neuropathy. I live over here in the US. I’ve never seen a case of tuberculous optic neuropathy in the United States. Let’s move on to examination. What about that? How does that help us? Well, acuity is not necessarily that helpful. Most optic neuropathies may or may not affect central vision. Sometimes there are some that acuity tends to be spared. For instance, glaucoma typically spares central vision until late. Optic disc drusen — and you’re seeing an autofluorescence picture here of buried optic disc drusen — this is another condition that typically does not affect central vision until later on. So if you see someone with disc drusen and decreased acuity and their field looks pretty good, it’s probably not related to the optic disc drusen. There are some optic neuropathies that tend to affect central vision in particular, and those include things like hereditary optic neuropathies, nutritional optic neuropathies, and toxins. But things like inflammation and infection may or may not affect central vision, and it’s not that helpful to me whether there’s just peripheral field loss or central field loss in differentiating most types of optic neuropathy. I would just mention — I forgot to mention — that you can type in questions at any point. We’ll get to questions at the end of the webinar. What about the visual field? Does that help? Well, this is the visual field that we’re seeing in patients in the optic neuritis treatment trial. I’m gonna discuss that in a little more detail in a moment. The point, though, really, of this slide is that in the optic neuritis treatment trial, you can see virtually any pattern of visual loss. So visual fields are not helpful to me in trying to figure out what kind of optic neuropathy it is. Because you can see anything. Virtually anything. Again, some exceptions that I expect to see central scotomas in toxic, nutritional, and hereditary conditions, and we’ll talk about that in the next webinar. And of course, the hallmark of optic neuropathy, or at least unilateral or asymmetric optic neuropathy, is the relative afferent pupillary defect. Here’s a patient — we covered this a couple webinars ago, if you were there — as we swing the light, you see that right pupil dilate, the left pupil constrict, because not as much light is getting down in that optic nerve. And so most people with relative afferent pupillary defects have optic nerve problems. If you have a bad retinal problem, of course, that can cause a relative afferent pupillary defect as well. But if there is unilateral or asymmetric vision loss from an optic neuropathy, there should be a relative afferent pupillary defect. So crucially important, of course, that you’re checking. How about eye movements? Does that help? Well, here’s a patient, and let me just — with blurry vision. And I’ll roll one video at a time. And you’ll see in this patient who has really just symptoms of blurry vision — she also has a problem with adduction of her left eye. This left eye is not getting all the way in towards the nose. And the right eye does. She has some abducting nystagmus. So she has a left internuclear ophthalmic lesion, which is something we see usually with demyelinating disease. So you need to look closely in a young person with what you think is optic neuritis, because if you see an internuclear ophthalmoplegia, then the diagnosis, at least in the United States, is almost always multiple sclerosis. This patient, whose eyes look pretty straight when she’s looking with this chin-up position, you’ll see that she has significant deficit in elevation of… I forget which. The right eye. And she has some lid retraction. She has thyroid eye disease. So don’t forget to look at the ocular motility. And the external exam, of course — we want to look to see if there’s exophthalmos. If you don’t have an exophthalmometer, you can improve your ability to detect small amounts of exophthalmos by looking down or up across the cornea. So you may see people who don’t appear to be proptotic, but if you look down or up over their corneas, you will be more likely to notice small amounts of exophthalmos. In this patient, she thought that the right eye looked rather large. She looks a little bit proptotic, but she really was not. She actually had mild thyroid eye disease and a little eyelid retraction. And then of course we’re gonna look at the slit lamp for other signs of inflammatory conditions. Very obvious keratitic precipitates in the upper left slide, and then these inflammatory nodules along the iris margin. This happens to be sarcoid granulomatous involvement, nodules, in the conjunctiva. So look for other signs of intraocular inflammation that may help with your differential diagnosis. And of course, the fundus in this patient with a very normal-looking nerve, and yet they have a relative afferent pupillary defect. We call this, by definition, a retrobulbar optic neuropathy. There may be mild optic disc swelling. In this case, this is the patient’s left eye and right eye. You can see obliteration of the optic cup, because those axons are swollen, and there’s mild swelling, no hemorrhage, no exudate in this case. And then of course a very markedly swollen disc with hemorrhage. There’s something abnormal-looking here in the macula, and this patient was seen just one or two days after losing vision. And here they are, ten days later, where this nice macular star has developed. Again, by definition, what we call neuroretinitis. And then other findings that you should look for in the fundus are extra blood vessels. So here’s a blood vessel. Looks like it goes nowhere. Another one. Tortuous. Where does it go? Well, in this case, there is an optic nerve meningioma that’s pushing on the nerve, and you can see these collateral vessels get big. So look for those. You can see some Paton’s lines here, folds in the choroid, which are due to mild swelling of the disc, pushing aside the retina and the choroid. Here are some radial folds in the retina, because something is pushing on the back of the eye. So look for these fundus findings. So let’s talk, then — we’ve sort of done the history, the examination, now we know what to ask and what to look for. Let’s talk about some of these entities that we’re gonna be discussing in optic neuritis. And remember, optic neuritis is a non-specific term, describing optic nerve involvement by inflammation or demyelination, and sometimes people will use the term optic neuritis even when they’re referring to infectious optic neuropathy. In the United States, when you use the term optic neuritis, certainly if you’re talking to a neurologist, they assume you mean MS. That’s not the case around the world. So here’s a very busy slide. The differential diagnosis of optic neuropathy, the major categories of inflammation, infection, hereditary, ischemia, infiltration, compression, and then a bunch of miscellaneous stuff. Today we’re gonna be talking about inflammation and infection. So here’s another polling question. Let me just — I need to try to pull down my poll. And… Question two. And I’m gonna launch the poll. So the question is: When you hear the word “typical” optic neuritis, so typical optic neuritis, what do you think about? And I’ll try to explain what I mean by this. But when you hear the word — maybe you don’t hear the word — but if you do hear the word “typical” optic neuritis, you tend to think of demyelination, you tend to think of idiopathic, infection, neuromyelitis — I’m sorry. That should say neuromyelitis optica. I left off an A there. What do you tend to think of? I’m gonna give you… Only about 12 votes. And there’s a heck of a lot more of you out there. So I guess if you just don’t hear the term “typical”, then don’t vote. I’ll give people about 10 more seconds. Maybe “typical” is not a word you hear very much. I only have about 12 people. The vast minority of people on the webinar. So… All right. I’m not seeing any more votes. I’m gonna end it there, and I’ll discuss what we’re talking about when we hear the word “typical”. Share results. So you can see that… Hopefully… Yes. You can see that the majority of people think of demyelination, although the vast majority did not answer this question. I’m gonna assume that means you don’t — perhaps you don’t hear the term typical, which is probably just as well. The reason I say that is that typical is a term that’s propagated somewhat, I think, in the US literature, and in the European literature. Typical, in the United States, usually means idiopathic or demyelinating optic neuritis. Whereas when people talk about atypical, they’re thinking of other conditions. Almost any other inflammatory condition. So neuromyelitis optica, sarcoidosis, autoimmune optic neuropathy, CRION, chronic relapsing inflammatory optic neuropathy, and other systemic optic neuropathies. And sometimes, as I said, sometimes people will even lump in infectious, including things like syphilis, Lyme, Bartonella — we’ll talk about these at the end of this webinar. So why do we call it typical? Well, because a lot of the literature out there is from the US, and from Europe, and, well, guess what? Here’s a legend over here, the highest incidence of multiple sclerosis is the dark green. Well, that’s most of North America and Europe. And so — and some of Australia. And so when you — since the people in these areas tend to publish a lot about optic neuritis, that’s where the term typical came from. So for me, in the United States, typical optic neuritis is demyelination. In China, typical optic neuritis may well be neuromyelitis optica, because that’s one of the most common, identifiable forms of optic neuritis they see. So instead of “typical”, let’s talk about demyelinating or idiopathic optic neuritis. Typically, in this case, the disc swelling is either going to be mild, or there’s going to be none. So you can have a retrobulbar optic neuropathy, as this patient did in the optic disc on top. There is no disc swelling. The old saying is: The patient sees nothing. The doctor sees nothing. The bottom disc shows mild disc swelling. And in demyelinating optic neuropathy, the disc swelling is either nonexistent — in other words, it’s retrobulbar — or it’s mild. There should be no exudate. No hemorrhage. And no significant swelling. And demyelinating optic neuritis is usually not dependent on steroids for recovery. We’ll talk a bit more about that. Whereas atypical optic neuritis — the disc swelling may be mild. It doesn’t have to be severe. It may be mild or nonexistent. But it may be severe, like we’re seeing here, with all this hemorrhage and exudate. And the important point is that atypical optic neuritis is treated differently than typical optic neuritis. So it’s important to diagnosis atypical optic neuritis, because these optic neuropathies are responsive to steroids and/or antibiotics, if you’re lumping in infectious, and you need treatment to improve vision. Not only that — but if you try to taper the steroids, they may relapse. And so you need to be careful about the tapering, and we’ll talk a bit about that. So what we know about demyelinating and idiopathic optic neuritis, at least in the United States, is from this optic neuritis treatment trial. In the optic neuritis treatment trial, the patients were young. They defined that as 18 to 45. You had to have a unilateral relatively acute optic neuropathy with symptoms of less than 9 days. You could have no other systemic diseases. Other than that. And in this study, they enrolled 459 patients. Only a couple got thrown out, because of abnormalities on their imaging. One had an aneurysm. One had a pituitary tumor. So what that means is that, at least in the United States, if the person presents with a unilateral optic neuropathy, of 9 days or less, very rare to have anything but optic neuritis. And here’s what I just said. So 2/3 of patients with typical demyelinating optic neuritis have retrobulbar optic neuritis, and 1/3 have disc swelling. Mild disc swelling. Sometimes this is referred to as papillitis. Inflammation of the papilla. In other words, the optic disc. Papillitis. And I showed you already this slide, again, trying to make the point that there is no typical visual field defect in demyelinating optic neuritis. You can see virtually anything. So I just covered this very briefly. I’m gonna poll people, just to see what they think. And let me get to question three. So the question is: Do corticosteroids improve the ultimate visual recovery in demyelinating optic neuritis? Do corticosteroids improve the ultimate visual recovery in demyelinating optic neuritis? And I’ll give you a few seconds to think about that. A lot more people voting now. All right. Slowing down here. I’ll give you another 5 seconds and I’m gonna close the poll. 4, 3, 2, 1. All right. Let’s end the poll. And I will share the results. Okay. So the majority — but not by a lot. The majority, almost 2/3, say no, and about 1/3 say yes, and the rest are not sure. So let me get rid of the poll, and I’m gonna move on to the answer. So here’s the answer. So the answer is: Steroids do not affect the ultimate recovery of vision in demyelinating optic neuritis. And this was the main outcome of the optic neuritis treatment trial. So they looked to see in these three groups of patients — one group got an oral placebo, sugar pill, one group got intravenous steroids, and one group got oral steroids. And what they found, even really by the first couple of months, they found that most people had what they called good recovery of vision. 20/40 or better. That would be 6/12, I believe. Is that right? 6/12 or better. And they called that good. Now, you talk to some young patients with excellent acuity in their other eye, they’re gonna say — that’s not so good. But that’s what they described as good. And you can see that the results — there is no statistically significant difference whether you got intravenous steroids, oral steroids, or placebo. So the intravenous steroids — or oral — do not affect the final visual acuity. They do affect the rate, but really pretty minimally. So the people who got the steroids were doing significantly better at month 1, but at month 2, they were not. So some people say — well, I don’t want the steroids if it’s only gonna affect the rate of recovery. As long as there’s no downside to not taking it for the ultimate recovery. Some people say — well, of course, I want to get better faster. Give me the intravenous steroids. And then they also looked at this study, at the development of multiple sclerosis, and so what they found was that, regardless of the MRI results, about half the patients with typical optic neuritis developed MS over 15 years. But if you had an MRI, and of course, they did, in this study — everyone got an MRI — about 3 in 4 patients developed MS if they had at least one typical plaque. And you’re seeing plaques on this MRI. These round spots here and here and here. Even here. Are plaques. If you have at least one, 3 in 4 chances that you’ll develop MS. If your MRI is normal, with no plaques, then only 1 in 4. But not zero. So atypical symptoms for demyelinating optic neuritis. In the older patient, older than 50, if there is no pain — 93% of people had pain — if there’s no pain, that’s a little red flag. You still can have it, but it’s a red flag. If it’s simultaneous bilateral, that’s pretty uncommon. If it’s progressing — so even patients who got the sugar pill had good recovery of vision. So if the vision is getting worse over more than a couple of weeks, that’s a big red flag that this may not be typical demyelinating optic neuritis. And of course, if it’s not getting better at all, then that’s also a red flag. Now, it’s possible that typical demyelinating optic neuritis doesn’t get better, but again, it should make you think about other potential issues. What about signs on exam? We talked about some of these already. If there’s hemorrhage around the disc, if there’s a lot of disc swelling, cotton wool spots, exudate, if there’s sector edema or pallid edema, the patient on the bottom right here has both pallid, very pale, white swelling, and it’s sectoral. The bottom part of this disc is not swollen. There’s also a cotton wool spot here. This is a patient who had giant cell arteritis. So let’s talk a little bit, then, about atypical optic neuritis. And this encompasses a number of conditions we’re gonna try to run through. Including neuromyelitis optica, sarcoidosis, autoimmune optic neuropathy, chronic relapsing inflammatory optic neuropathy, and others. And then infectious we’ll talk about at some point towards the end. So neuromyelitis optica, or Devic’s disease, formerly, hopefully, known as Devic, which is the name of a guy — an eponym — we’re trying not to use those. But formerly known as Devic’s — is an idiopathic inflammatory demyelinating central nervous system disease. When I was a resident, which was a long time ago, you only really thought about neuromyelitis optica if you had a young person who was blind in a wheelchair, because to even think about the diagnosis, they had to have both optic neuritis and vision loss, in addition to transverse myelitis. So inflammation in the spinal cord that causes some degree of paralysis. So it was sort of what we call a self-fulfilling prophesy. You only thought about the condition under those circumstances. But like most conditions, once there’s a test, the phenotype — that is, what you see and what you can ascribe to the condition — expanded. And not that long ago, about ten years ago, there was discovered what’s been now called the NMO (audio dropped). And this is reported specificity as high as 95 to 100%. The (audio dropped) showing multiple spinal cord — you can see enhancement in the spinal cord — multiple spinal cord lesions in a patient with neuromyelitis optica. Brain MRI findings not satisfying MS. So, in other words, if you have these problems and the brain MRI looks pretty good — because normally with MS, you’ll see plaques — and then, of course, if your blood test is positive. As far as treatment of neuromyelitis optica, this was a relatively recent study that looked at several of the medications that were used. So rituximab, mycophenolate, and azathioprine. And it was a retrospective study between Mayo and Johns Hopkins, looking at relapse and treatment failure. And they found fairly good responses to the rituximab and the mycophenolate. Maybe not as good as the azathioprine. With fairly good remission rates. Not 100%, by any means. And markedly reduced relapse rates. And they did note that if you weren’t doing well — so if you relapsed on one of these medicines, you could switch to one of the other ones, and if that happened, the patients did fairly well on the second medication. In terms of NMO optic neuritis treatment, we know that initial treatment is the same as one would consider for demyelinating optic neuropathy, and that is intravenous corticosteroids for 3 to 5 days, a gram of Solu-Medrol per day. However, in patients who don’t have good response within — towards the end of those 3 to 5 days — we fairly rapidly can consider plasmapheresis. The data — there’s no randomized, controlled clinical trials on this. So I can’t quote you excellent evidence-based medicine. But there certainly have been some papers that are suggestive, that, if the steroids aren’t working, plasmapheresis can be considered. And I know certainly anecdotally, we have several patients in my practice who really had no significant improvement after 3 to 5 days of steroids, and then they had plasmapheresis, and at least one went from no light perception to 20/20 or 6/6 vision over the next few weeks after plasmapheresis. So, again, totally anecdotal, but there are some publications indicating that this may be effective. And now, given this NMO antibody that we talked about, and this blood test, there’s something that’s come up — the NMO spectrum disorders. And we’re learning more and more about this condition, as time goes by, as we now have this condition. And so now somebody who may not fit the criteria for a definite diagnosis of NMO — let’s say they just have a positive antibody, and no transverse myelitis. Let’s say optic neuritis and a positive NMO — they don’t really fit the criteria for NMO. So it’s called NMO spectrum disorder. And additionally, they’ve identified more recently this myelin oligodendrocyte glycoprotein, or MOG, antibody. This is, I believe, not available commercially. Certainly not around the world. And I don’t think in the US either. It will probably become so, just as the NMO antibody has become available commercially. And there even have been a couple reports, as this one from Soto and Associates, looking at the differences between anti-MOG and anti-aquaporin-4, or NMO, and they found that the patients with MOG are more likely to be male, have bilateral optic neuropathy, with single attacks and better recovery. So if you haven’t heard about the anti-MOG antibodies, you will, at some point in the future. There have also been some studies that have looked at MRI findings, to try to differentiate optic neuritis in NMO versus (inaudible) MRI that could help us. Be more or less suspicious for NMO. And in this paper, which was retrospective, they looked at 26 patients with NMO and 26 with MS, and what they found was that NMO tended to cause more extensive involvement of the optic nerve, in terms of the enhancement. So on the MRI in the bottom left, there’s the inflammation — is right here in the optic nerve, whereas — and that would be more typical for demyelination. Whereas in NMO, they found longer segments. And their cutoff was this 17.6 millimeters. Which is a fairly long degree of inflammation. And that would be sort of a red flag. Hey, this may not be demyelinating, if you’re thinking demyelinating. Subsequently, another study looked at — and this is just from 2016, from the journal Multiple Sclerosis. What they found — they looked at patients with both demyelinating aquaporin-4 and MOG, and found that it was more common to be bilateral in the aquaporin-4 and MOG than MS. And I mentioned that earlier. I do not see simultaneous optic neuritis in MS, in general. Chiasmal and optic tract involvement was more common in aquaporin-4 or NMO, and there was longer segment involvement. So it kind of corroborated the previous study. Longer segment involvements on the MRI, in NMO and anti-MOG. All right. So we’re gonna switch gears a little bit to sarcoid. And depending on where you live, again, this may or may not be that prevalent. Here’s a patient with a markedly swollen disc. So the first thing — you should look at this and say — even if you were thinking — oh, this is gonna be typical optic neuritis, maybe this is gonna be demyelinating, as soon as I look at this nerve, I’d say — no, this is not demyelinating. There’s hemorrhage. There’s exudate. There’s a very swollen optic nerve. So I’m gonna think about atypical optic neuropathies. I’m gonna think about NMO. I’m gonna think about sarcoid. And we usually check an angiotensin converting enzyme. You want to look closely in the periphery, to look for any vasculitis. There’s a little sheathing of the vessels here, that would be seen in inflammatory optic neuropathy. Of course, chest x-rays are these days more commonly in the US, at least, CT scan of the chest — may show hilar adenopathy in sarcoidosis. Sarcoid is usually very — usually very sensitive to oral corticosteroid treatment. Other atypical optic neuropathies — and this one, chronic relapsing inflammatory optic neuropathy — kind of a mouthful — also known as CRION — and as you’ll see from the definition, it’s not really a diagnosis. Basically it’s kind of a — if you have a steroid response and steroid-dependent — that means if you treat them with steroids, they get better. You stop the steroids fairly rapidly, and they get worse. So steroid responsive, steroid-dependent optic neuropathy that’s not sarcoid — they have no other neurologic, systemic, or ocular disease, that’s CRION. So it’s a kind of a grab bag of basically idiopathic, atypical optic neuritis. But patients like diagnoses. So if you tell them — I don’t know what you have. There’s no answer — versus — you have CRION — patients seem to like that. So, again, I don’t think it’s actually an entity so much as hopefully — as the time goes by, in the future — we’ll figure out what these types of optic neuropathies really are. And have good ways to treat them. Along these lines, there’s a different condition — the CRION descriptions come from the United Kingdom. Autoimmune optic neuropathy is from the US. And one question might be: Well, could there be some overlap here? So this is similar, you’ll see — recurrent optic neuropathy that requires steroids. The antinuclear antibody blood test or the anticardiolipin antibodies can be a marker. But certainly not specific. If I’m thinking about this condition, which I fairly rarely do, but when I’m thinking about it, I check these blood tests first. Part of the diagnosis is, again, like the CRION — no other vascular problems, systemic problems. And the way that you can diagnose this, theoretically, definitively, is with biopsy of non-sun-exposed skin that shows evidence of vasculitis. And both of these references here discuss this in more detail. You can see the term was coined way back in 1988. We don’t know a heck of a lot more about it now, I’d say, than we did then. I’d also look at this as kind of a grab bag, but I’m not sure I personally have ever seen a definite case of autoimmune optic neuropathy. So here’s another polling question. Let me see if you guys have been paying attention. We’ll get set for this poll. And… Hold on. I’m not seeing… Huh. It’s not letting me move on to another polling question. Oh, stop sharing. That would be the answer, probably. Yep. Question 4. Okay. So question 4 is: Which of the following is a way to differentiate demyelinating optic neuropathy or optic neuritis from atypical optic neuritis? And let me… Sorry. I haven’t launched the poll. So don’t… Okay. Now you can vote. Is it the presence of pain? Does that differentiate? Is it severe optic disc swelling? Is it no plaques on the MRI? Or good visual recovery? So which of these four things is the best way to differentiate demyelinating optic neuropathy from atypical optic neuritis? So we’re talking about differentiating. Which one differentiates, tells us this is or is not demyelinating? I’ll give you a few seconds to think about it. Somewhat more than half of you have already voted. And I can tell from the results that it’s not an easy question. Okay. I’m gonna call it. I think most of you voted. I’m gonna end the poll and show you the results. So certainly the majority here got the question correct. Severe disc swelling. So the reason this is the best differentiator is because if you have severe disc swelling, you do not have demyelinating optic neuropathy. Period. So number 2, severe disc swelling, is the best way. Now, do people with demyelinating optic neuritis have pain? Usually yes. Not every time. So you can’t use it. And plus patients with non-demyelinating optic neuritis have pain. So the presence of pain doesn’t help at all. Because when I see someone with atypical optic neuritis, they usually have pain too. No plaques on the MRI. Well, we said most people do have plaques. But 25% of people with no plaques go on to develop multiple sclerosis. And good visual recovery. It’s true. Most people with demyelinating optic neuritis have good visual recovery, but hopefully most people with other forms of inflammatory optic neuropathy also have good visual recovery. So although all of these things can occur in demyelination except disc swelling — severe disc swelling — so severe disc swelling is what I was looking for. It may be a tougher question. All right. Let me get out of there and move on. All right. So let’s talk about infectious optic neuropathy next. And I’m not gonna say a heck of a lot about this, but we’ll talk a bit about it. And part of my main message from this infectious discussion is that, depending on where you live, that’s what you’re gonna see, infectious-wise. So if you live in South India, maybe the Chikungunya virus is gonna be common, as was indicated in this case report. Now, the Chikungunya virus has moved, over the last few years since this report, to at least Latin America. So it’s no longer just in India, as happens with global travel these days. So when do you think about infectious optic neuropathy? Or sometimes — and I shouldn’t use the term — I don’t like the term infectious optic neuritis. I would use the term infectious optic neuropathy. But at least if you use infectious optic neuritis, I’ll know what you’re talking about. When do you think of infection? So if there’s some sort of systemic illness that suggests a virus, or some other problem that’s infectious. If there’s bilateral, simultaneous disc swelling. That should be a red flag for — hey, maybe this is infectious. If it’s atypical demographic. So if the person is older or much younger for demyelinating, you wanna think about infection. If there’s some sort of immune compromise, immune system compromise, the person was on chronic immune suppression, for some reason. If you see this picture — again, I mentioned this a couple of times already — of neuroretinitis. That is disc swelling plus a macular star of exudate. Think about infection. And of course, if there are any of the other associated signs that we saw early in the talk, early in the webinar, of intraocular inflammation, you’re gonna think about infectious. Now, it doesn’t mean that you can’t have other signs of intraocular inflammation with some of these other conditions like sarcoidosis. But you’re gonna think more strongly about infection, if you have any of these issues come up. All right. So this is really — there’s no correct answer, as you can see, to this question. Hold on. Let me set up the polling here. And the polling is open. So I’m just curious. In the people on the call, which of the following is the most common infectious optic neuropathy that you see where you live? Is it Bartonella henselae, which is cat scratch? Is it tuberculosis? Is it syphilis? Or is it CMV? And maybe this won’t really help me, because I don’t know where all of you are from. But perhaps Orbis has a way to track where people are from. I don’t know. But I will see what — at least I’ll get a feel for what the people on the call are getting. Most common infectious optic neuropathy. If you have to pick one of these things. Since I don’t give you an option for picking more than one at a time. All right. I think most people have voted. Give you another 5 seconds. The last entries. Okay. I’m gonna end the poll and show you the results. So pretty mixed group, I think. So tuberculosis, most common. Syphilis, second. Bartonella, third, and CMV, fourth. For me, it’s gonna be — my own experience — would be, of these conditions, Bartonella, one, syphilis, two, CMV, three, and TB, four, for me. And for probably most people in the US. Probably would be that as well. All right. Let me just get out of here. So let’s talk about the one I see most commonly, which is Bartonella henselae, or cat scratch disease. And here’s another patient with a mildly swollen disc. It’s somewhat in the resolving stage, with this macular star of exudate. It’s not maybe a complete star, but a pretty complete star. There are also some little exudates here that we think we’ve now identified as occurring in cat scratch disease or Bartonella henselae. So when I see somebody with neuroretinitis, I’m gonna think cat scratch. It can be idiopathic. For me, it’s almost always cat scratch or idiopathic. For those of you who live where there’s toxo, syphilis, TB, you might see neuroretinitis. But think about infectious, if you see neuroretinitis. It’s not multiple sclerosis. And I’ve seen patients sent to me with optic neuritis, they’ve got all their multiple sclerosis support group literature in hand, and they don’t have MS. This is not associated with MS. And just as a little point to make sure everyone’s aware of — and I showed this earlier — here’s a patient that we’re seeing 3 days after their symptoms started. A very swollen nerve. Not typical optic neuritis. Not demyelinating. There’s a little hemorrhage. And there’s something going on in the macular area. You can kind of get a feel here. I hope you can all see my pointer. You can get a feel here that there’s something that’s not right. But there’s no star of exudate. And the retina specialist said — yeah, there’s no exudate. I said — if there’s fluid in the macula, that’s similar to having exudate. Especially after 3 days. Get the blood test. In my case, for cat scratch and syphilis. And then let me see the patient. And I saw the patient a week later, and here they are now, that same patient, with that very nice-looking star of exudate, in someone with obvious neuroretinitis, and a positive blood test for Bartonella henselae, or cat scratch disease. And so you can often but not always see tender cervical lymphadenopathy. This is actually rather a unique case, where a patient was actually scratched on the eye by a cat. And this was cat scratch granuloma, I suppose, of the conjunctiva. Here’s just that spot in the bottom here that I saw in a patient who didn’t really have any macular edema. Just this spot with a positive cat scratch test. Treatment — we use ciprofloxacin, doxycycline, sometimes rifampin, depending on where you live. Here’s a patient with a very swollen nerve, hemorrhage, exudate, not typical optic neuritis. Not demyelinating. Here’s their retinal periphery. So the point, again, is: Make sure you don’t just look at the central fundus. CMV may cause a “isolated” papillitis. Make sure you look in the periphery. Don’t see a lot of it in the US, outside of HIV. Syphilis can cause almost any of these things. It can cause a papillitis, meaning optic disc swelling. It can cause a neuroretinitis, it can be retrobulbar, so it can cause almost any appearance of the back of the eye. Tuberculous optic neuropathy, which, as I’ve said, I have very little experience with — the literature says that most patients with tuberculous optic neuropathy have disc swelling. And most, 80%, have uveitis in addition. So I think if you live in an area where there’s a lot of TB, and you see swelling of the disc, look for other signs of uveitis and certainly maybe TB. And, again, here’s just a funny kind of a plot. The countries are enlarged or thinned, depending on how much syphilis you have. So you can see that where I live, in the United States, up here, not much syphilis. In Africa, India, other Asian countries — a bit more syphilis. And as I said this already — again, depending on where you live, different infectious optic neuropathies are gonna be more common. So here, incidence rates for TB around the world. And then I mention herpes zoster, partly because I just got back from the American Academy of Ophthalmology meeting yesterday. We actually had a poster on herpes zoster optic neuropathy, and had a number of people come up and say — oh, I’ve seen a case of that. It’s not widely reported. It’s something that can occur within several days to a couple of weeks after the onset of the herpes zoster rash in the V1 distribution, of course, ipsilateral to the V1 involvement. There may or may not be disc swelling, and the visual prognosis is, I’d say, mixed. And that’s what our study showed. I’m interested. We have, as I mentioned, a number of people come by the poster. We’re gonna try to collate all those patients and write an article. So if anyone out there has a case of herpes zoster optic neuropathy that’s well documented, let me know. I’ll put you on the paper. All right. Let’s go to our test answers. So… The question was… Three patients. Subacute vision loss. Is the workup the same? Is the differential diagnosis the same for each of these patients, based on their fundus appearance? Here’s the first optic nerve. So this nerve is rather swollen. It’s too swollen to be typical idiopathic or demyelinating optic neuritis. What’s the workup? We’re gonna look at MRI, chest x-ray, NMO, ACE, lysozyme, cat scratch. We’re looking for sarcoidosis, Bartonella, NMO. Final diagnosis in this patient was sarcoidosis. They had 20/400 vision. We started them on oral prednisone, and within about 2 weeks, they were 6/6 from legally blind. Patient number 2 has disc swelling, more disc swelling than you should have for typical or demyelinating optic neuritis, plus a macular star of exudate. So we’re gonna be thinking possibly infectious. And in this case, we’re going to be looking — we’re making a diagnosis of neuroretinitis. In this case, we looked at syphilis and Bartonella, because that’s what I see where I live, although mostly Bartonella. And indeed, this person had positive Bartonella henselae titers, and was treated with ciprofloxacin, and had pretty good recovery of vision. Not quite to normal. From 20/200 or 6/36 to… I believe this person came back to 6/12. And then our last patient, who had a normal-looking optic disc, and the other disc looked the same as this, and retrobulbar optic neuropathy, but the onset was fairly acute, there was pain and pain with eye movement, this would be — certainly could be compatible with any inflammatory optic neuropathy, but certainly where I live, most consistent with idiopathic or demyelinating optic neuritis. So we’re gonna get an MRI in this patient. We are not, in my world, going to order any blood tests whatsoever. We’re gonna get an MRI, and if there are plaques, talk strongly about intravenous steroids. I didn’t really mention that in the other part of the webinar. But as I said, from a visual standpoint, the main reason to give the intravenous steroids is more rapid recovery of vision, but not ultimately more recovery of vision. The other benefit of the steroids I didn’t mention is that, when they followed these patients over the first couple of years, if you got the intravenous steroids, less people developed definite MS than who didn’t get the intravenous steroids. However, after two years, that effect goes away, and the group catches up. So in summary, most optic neuropathy in young adults is inflammation or infection. The prevalence of many optic neuropathies depends on where you live and what conditions are common. What infections are common. It’s important, though, to make a correct diagnosis, of course, because vision recovery may depend on it. They may need steroids. They may need antibiotics. Depending on what form of inflammatory optic neuropathy is present. Okay. So I’m gonna go to the questions. Except I can’t… Let me see if it will let me. Hm. Well… I’m trying to go to the questions and it’s not… There they are. Q and A. Let’s see what we’ve got. Okay. So one question. Solu-Medrol only with plaques? Actually, sorry. Let me start with the oldest question first. I’ll get back to that. How do you manage recurrence of retrobulbar optic neuropathy? So, again, if there’s recurrent retrobulbar optic neuropathy, of course, as I just mentioned, I’m gonna get an MRI, looking for plaques. If there’s no plaques, then I’m gonna offer the patient intravenous steroids for more rapid recovery of vision. If they get better and then they recur, I’m gonna say — oh, okay. It still could be demyelinating or typical optic neuritis. But I’m gonna think more about NMO at this point. Now they’ve had a couple of episodes of isolated optic neuritis. And that’s what I’m gonna do. Let’s see. Okay. Someone wrote very rare really… So I don’t know what that means. There’s a question… Neuroretinitis and tuberculosis occurs at the time of the active disease or after? I think it could be either. But I will say that, as I said, the only times I ever see tuberculous optic neuropathy is when I go to countries where it exists and I see patients. So I’m not positive about that. But certainly it occurs at the time of that disease. I think that if you live in an area where there’s TB, even if the patient is not thought to have active TB, I would certainly consider it in the differential diagnosis. Here’s the question about Solu-Medrol, only with plaques. So it’s not necessarily… I tell people who I think have typical/demyelinating optic neuritis — there are basically three reasons I consider intravenous steroids. One, if there’s a lot of pain. And usually there’s not. It’ll make the pain go away really fast. So that’s one reason I offer it to patients. Hardly anyone wants intravenous steroids, because the pain usually isn’t that bad. Two, I tell the patient: On average, if I see the patient within the first couple weeks, again, it’ll make your vision improve more rapidly than if you don’t get the steroids. Some people say great. I want to get better faster. Some people say — forget it. I don’t want intravenous drugs just to get better a little faster. And then the third reason is: If they have plaques, that increases their risk of getting MS. And if they get the intravenous Solu-Medrol, it decreases the chance of getting MS over the next 2 years. But after 2 years, that protective so-called effect goes away. Hold on. Let me scroll back. Hold on. Let me find out where I am. Toxoplasmosis could be related — I think it could be. I think it’s really rare, at least where I live. There’s some toxo. I’ve never seen a case of toxo. Usually if it’s toxo, you’re gonna have a significant uveitis, significant vitreal reaction, and that would be the big red flag. Lots of vitreal cell — then I would certainly think about toxo. I personally don’t see toxo optic neuropathy much at all. Okay. Let’s see. Young female with vision loss. Severe disc edema. MRI, granulomatous, calcified lesions in the thalamus. So certainly in severe disc edema, we’re out of the demyelinating realm — that person probably needs a spinal tap, if they haven’t had one. Looking for — I’m not sure. Certainly you can… Calcified lesion in the thalamus? I don’t know if that’s a red herring, meaning not related. That person probably has… Certainly has an atypical optic neuritis. Might have infection. And I would do a spinal tap, if that’s not already been done. I would certainly check for syphilis, just because that can do wacky things. Tuberculosis and so on. Is there any neuroprotective medicine to improve final vision acuity in idiopathic optic neuritis? Not that we know of. And I’m talking about the demyelinating/idiopathic — is there anything we know that actually is better than nothing in terms of the ultimate visual recovery? No. Any optic neuritis in less than 18 years? So certainly any of the things we just discussed can occur in less than 18-year-old patients. Demyelinating optic neuritis is not as common in that age range. But I certainly see it. I’ve seen it as young as age 4. Any of those infections can occur. So being less than 18 doesn’t help me much. I think a postviral optic neuritis is more common. I want to know… Is the pattern of visual defect of prognostic values? Well, in terms of visual recovery, sure. If you don’t have central vision loss, then you have a good chance of having good central vision. If you have bad central vision and central scotoma, it’s less likely that you’ll have good recovery. The other sort of visual prognosis factor, prognostic factor, is that bad vision loss does not as often get as good as good vision loss. That sounds like it doesn’t make sense. What that means is that in the optic neuritis treatment trial, although I showed you data that showed that 93% of people had good recovery of vision at 20/40 or better, if you subdivided all the patients, and you just looked at the group of patients who were count-fingers, hand motion, light perception, or no light perception, only about 50% of those came back to 20/40 or better. Would you always suggest patients with a first attack of retrobulbar… Yes. To perform an MRI? Yes. We do, in the United States. Because we’re looking for plaques. We’re looking for their risk of MS. So I do recommend that. How do you manage pediatrics who present with optic neuritis? I think pretty much the same way that I do with adults. I think the differential is a little bit different. They more often — pediatrics more often have bilateral involvement. And idiopathic postviral optic neuritis. At least, in the United States. But depending on where you live, that may be different, and it’s a tough one to answer. I don’t manage them really much different. Neurologists reference in VEP — how important before starting treatment? Not important whatsoever, unless they have lots of other neurologic symptoms. But certainly I never — I shouldn’t say — I always send my patients with optic neuritis and plaques to a neurologist. Plaques on an MRI. I usually don’t send them to a neurologist if there are no plaques. VEP, in my opinion, is never necessary. Unless you can’t be sure, if you’re not sure if it’s optic neuritis, or unless you’re looking for an old episode of optic neuritis, where all the signs have improved. The VEP can be normal forever. Even if the person has good vision recovery. I never personally order VEPs in someone who has obvious optic neuritis. Do you consider MS as a differential diagnosis in ME? I’m assuming is macular edema — and intermediate uveitis? The answer is you have to… It certainly can… You can see uveitis in MS. Personally, I almost never see it, but that may be a referral bias, because people in my practice — people with uveitis get sent to my uveitis specialist. So he says he does see it, and in large studies that look at kind of tertiary uveitis centers, as many as 11% or 12% of the quote-unquote idiopathic uveitis patients develop MS. That’s a very select group. So it definitely happens in MS. And typical optic neuritis does not improve — yes. So 93% of people improve. That means that 7% don’t. Does all… Yes. Does all neuroretinitis have a macular star? Neuroretinitis, by definition, by definition, is disc swelling and a macular star. So the answer is: You cannot diagnose neuroretinitis without a macular star or partial macular star. How long do you give the IV steroids and then you change to oral? So I usually do what the optic neuritis treatment trial did, and that is 3 days of intravenous Solu-Medrol, 1 gram per day, and then I usually do treat them with 2 weeks of oral prednisone. A lot of our neurologists use 3 to 5 days of intravenous Solu-Medrol, with no oral prednisone. And the oral prednisone is typically 1 milligram per kilogram per day, for 10 days, and then a rapid taper over 4 days. 10-year-old girl, sudden loss of vision in one eye. All blood tests normal, MRI normal, slight improvement to hand motion after 2 months. So I assume that girl also has a big relative afferent pupillary defect. And that’s not mentioned here, what their fundus looked like. So I won’t comment further. If patient appears to have typical optic neuritis except for the fact that the patient is a pediatric, do you give steroids? Yes. If the patient can afford IV steroids — can’t afford — can oral steroids work? Yes. So there have been a couple of studies — one, a big study in Japan — that looked at — instead of giving IV, giving large doses of oral prednisone. How much? 750 milligrams a day. I do occasionally write that for patients in the US. We can get 50 milligram prednisone pills. I send the prescription to the pharmacy. And I always get called to say — hey, are you sure? You must have miswritten this prescription. But you can give 3 days of large doses of oral steroids, which is, I think, a very good and very important question, because around the world, of course, intravenous steroids may have different costs, and people have different abilities to pay for it. Do you work up with optic neuropathy to rule out infection before starting steroid? Not if I don’t see any of the atypical signs of optic neuritis we just talked about. If I see any of the things — if it’s bilateral, if there’s any uveitis, if there are any other systemic illnesses, all those things. But if I don’t, then I do not. And now, if you live in an area with lots of TB, you’re probably gonna want to check TB in everybody. Let’s see. How frequently do you see patients with optic neuritis with no MRI lesions? Frequently. And again, it depends, I guess, if you’re talking about typical demyelinating, then I see that about a third of the time, probably, with no plaques. Or at least a third of the time. Of course, if it’s atypical, then I routinely see normal MRIs. Okay. Fundus normal. I guess that was for the young girl. I’m assuming they’ve got a big APD, because if they don’t, they’re faking. Is there any role for the new medication Rebif for isolated optic neuritis? No. I mean, those are not… Those medications are not used for acute MS or for anything related to MS. They’re to try to prevent recurrences of MS. But they have no role in acute optic neuritis. Is it always necessary to rule out infectious… Okay. That’s the same question I just answered. Do you commonly see sinusitis as a cause for optic neuritis? I do not. I extremely rarely see it where I live. In fact, I’m trying to think back… I probably have not seen it in the last 10 years. Okay. That is the end of my questions. So I want to thank everybody for attending the Orbis optic neuropathy part I webinar. We will do — I don’t know when yet, sorry — we will try to do an optic neuropathy part II and conclusion next time. It will be… Let’s see. It will be regarding ischemic, hereditary, nutritional, and compressive optic neuropathies. So… I will be — if any of you are from Africa, I’ll be traveling. Maybe I’ll see you in South Africa, Uganda, and Kenya, where I’ll be over the next 10 days. Look forward to seeing everyone, or at least, sort of seeing everyone. I have to get my video working next time. Next time. And… Let’s see.

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October 19, 2016

Last Updated: October 31, 2022

1 thought on “Lecture: Optic Neuropathy, Part I”

  1. Dr. GOLNIK, Thankyou for sharing the optic neurits lectures. By trade, i am a engr. Though i am technical, a lot of info on the web about MS and optic nureopathy is overwhelming, boring and confusing. Your lectures is very organized, easy to follow, and validated.

    Please keep sharing info.. Awareness helps us all get treated appropriately for different diseases and to make smarter /more effective choices with our medical regimen/medicine.

    If you have written any books or publishments please send me a signed copy. You can email me and I can send you my address. Again, you are so talented and have found your gift in teaching and touching the hearts of many that want to learn more and those that can relate to your teachings. #thankyou
    – Kali


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