Lecture: Optic Neuritis: Etiology, Evaluation, and Management Updates

DR MACKAY: Hello, and welcome, everyone. So today we’re gonna be talking about optic neuritis. So I’m Dr. Devin Mackay, and I’m the director of neuro-ophthalmology at Indiana University. This is the second webinar I’ve given for Cybersight, and the first one was on myasthenia gravis, which I believe is in the archives. And I look forward to spending this time with you here today. So I think we’ll go ahead and get started. Okay. So let’s talk about our objectives for today. What I’m hoping that you’ll be able to get from this webinar is that you will be able to, number one, describe typical versus atypical optic neuritis. And the implications that that has for testing and treatment. This is a very helpful construct, clinically, that can help us know what kind of additional testing may be needed for some patients with optic neuritis. Also we’ll review some of the data that underlies the evidence-based practices in the treatment of optic neuritis. And we’ll also be able to compare and contrast idiopathic optic neuritis with other forms of optic neuritis, such as that associated with NMO spectrum disorder and anti-MOG associated optic neuritis. So first, what is optic neuritis? We have a great variety of people who are joining us today, some of whom are trainees, and some are even neuro-ophthalmologists who have been in practice for some time. So we’ll have some basic concepts, as well as some more advanced concepts as part of the webinar today. I would define optic neuritis as dysfunction of the optic nerve that is related to inflammation. And so we can consider all optic neuropathies under a large umbrella, and optic neuritis would be a subset of that. And that would be to distinguish it from other non-inflammatory optic neuropathies. Optic neuritis can also be used as a term to describe optic nerve dysfunction associated with infection, for example. Or with inflammation associated with other systemic conditions. Today we’ll be talking about it mostly as an autoimmune related disorder. And so we’ll approach it from that perspective today. With regard to the pathophysiology of optic neuritis, it is characterized by inflammation and often demyelination of the optic nerve. And that happens from swelling of nerve tissue in the area of demyelination, and that is followed by myelin sheath breakdown, and then destruction of nerve fibers. The consequence of the myelin sheath breakdown is that nerve conduction through the optic nerve slows down. And some of it also decreases altogether. And when optic neuritis recovers, the myelin is restored to some degree, but it’s not done so perfectly. And that results in some of the permanent decrease in vision that we sometimes see, after a case of optic neuritis. Now, what are some of the risk factors for acute demyelinating optic neuritis? Many of us are familiar with these. It includes a young age. In fact, optic neuritis is the most common acute optic neuropathy in young adults. Also a female gender is also a predilection. And this depends on someone’s race as well. We know that in certain European cohorts, the ratio of women to men with optic neuritis may be as high as 3 to 1. Whereas in Japanese cohorts, it may be more like 1.2 to 1. We obviously know that a history of multiple sclerosis is a risk factor for optic neuritis. And also a Caucasian race is also a risk factor. There are other risk factors that have been determined as well. Such as someone’s latitude, geographically, where they live. It turns out that higher latitudes are also more often associated with optic neuritis. Now, what about the patient history? So one cardinal feature is pain. And the pain is typically in or around the affected eye. And interestingly, it can happen up to several days before the vision loss. I’ve had a number of patients who have come to me, where the very first complaint was pain. And some patients have the pain happen at the exact same time as the vision loss. The pain is often worse with eye movement. And that was true in about 92% of patients with optic neuritis in the optic neuritis treatment trial. Pain is usually a sign of orbital optic nerve involvement. So there was a paper by Fazoni et al. in 2003 that looked at the segments of the optic nerve and bulb when there was pain, and they found that the pain was much less frequent when the orbital nerve segment was spared. If we divide the optic nerve into an orbital segment, the part in the orbit, a canalicular segment, which is the segment that passes through the optic canal, and the intracranial segment, which is between the optic chiasm and the optic canal, if we divide the optic nerve into those three sections, and we consider all optic neuritis that left out this orbital section, we would have found that pain was present only about 32% of the time. A great difference. And I bring that up to help us realize that not all optic neuritis involves pain. Yes, a vast majority does, but it does not rule out the diagnosis, if the patient has painless vision loss. And then, of course, vision loss is the other cardinal part of the history that suggests optic neuritis. Most often, the central vision is affected. Often there is color desaturation. Patients may describe that as colors being muted, or washed out, or pastel. And interestingly, photopsias are reported in a significant minority of patients. About 30%. The vision typically worsens over several days, up to about two weeks. It’s rare that the patient would have a maximal onset of vision loss right at the onset. That would usually be more suggestive of an ischemic disorder. The visual recovery begins within 2 to 4 weeks, following the onset, in a typical case of optic neuritis. Further improvement is possible even up to one year, or sometimes even longer, from the onset of the vision problem. Most of the improvement happens before that, within months after the optic neuritis episode. In the optic neuritis treatment trial, we learned that these patients got a lot better with their vision. That is a cardinal feature of optic neuritis. The vision should get a lot better. In fact, less than 10% had a visual acuity worse than 20/40 after one year. Another way to say that would be that greater than 90% of patients had vision better than 20/40 after one year in the affected eye. Another interesting finding was that 56% of the visual field defects resolved after one year, and 73% by ten years. Implying that there is some small amount of additional visual field improvement that happens even years after optic neuritis onset. Now, what about the examination? The examination should demonstrate impaired visual acuity and contrast sensitivity. We often don’t test contrast sensitivity, or at least, most of us don’t, in a clinical setting. But it has been used as an outcome marker in some trials regarding optic neuritis. A relative afferent pupillary defect must be present, if there is asymmetric or unilateral optic neuritis. The impaired color vision is typically out of proportion to the visual acuity impairment. In other words, the visual acuity may only be mildly affected. Whereas the color vision can sometimes be profoundly affected. Color plate testing was abnormal in about 88% of patients in the optic neuritis treatment trial. Again, showing us that fairly normal color vision by that test would again not rule out the diagnosis of optic neuritis, but the vast majority of cases will have problems with color vision. And of course, a visual field defect is also associated. Now, what about the funduscopic examination? In acute optic neuritis, it is completely normal in about 2/3 of cases. Optic disc pallor is typically a feature, but again, not acutely. It takes about 4 to 6 weeks for pallor to first be noticed on a funduscopic examination. Optic disc edema is present in about 1/3 of cases, acutely. Peripapillary hemorrhages and exudates are very uncommon, and should make you think about an alternative diagnosis if you do see them. And same with uveitis. It’s also uncommon in typical optic neuritis. And should… (audio drop) idiopathic demyelinating optic neuritis. The optic neuritis workup starts with this most important test, which is an MRI. An MRI in an ideal world — we would want to do an MRI of the brain and orbits. In the United States, and perhaps some other countries, there can be insurance restrictions that don’t allow us to get both of those tests simultaneously. And you may have to choose which one is more important for your clinical circumstances for the patient you have. However, if you can get brain and orbits, why would we do both? What would be the importance of that? For one, an MRI of the brain is the best predictor we have for the risk of multiple sclerosis in patients with optic neuritis. And in some cases, may even provide the diagnosis, even if the patient has no other clinical history of any other demyelinating attack. If the patient has at least one brain lesion found at the time of their optic neuritis attack, the risk of multiple sclerosis is about 72% over 15 years. It’s much lower if there is no brain lesion found on MRI at that time. The risk is about 25% over 15 years. This can help you and the patient know how much surveillance is necessary in the future to help detect any multiple sclerosis that may be diagnosed in the future. The orbital section of the skin is very helpful in several ways. One is that it is able to detect enhancement of the optic nerve, which is present in about 95% of cases of acute optic neuritis. And that is helpful in confirming the diagnosis. Especially if there’s any doubt based on clinical findings. The orbital scan also includes an orbital protocol, which is performed with orbital fat suppression. That suppresses out the rest of the fat in the orbit, so that you can see the optic nerve more clearly and help make a determination whether the nerve is abnormal or not. Further testing beyond an MRI may not be needed for typical optic neuritis. My own clinical practice is that I do not do additional testing if someone has a very classic case of optic neuritis, other than the MRI of the brain and orbits. If there are any atypical features, which we’ll go over later in this webinar, then that would be a prompt for additional testing. Here’s an example of some imaging findings that may be typical on a patient with optic neuritis associated with multiple sclerosis. In panel A, we see some faint enhancement of this patient’s right optic nerve. And this is in the orbital segment. In B, we see a coronal section, where again we see some enhancement of the right optic nerve, if we compare it to the left. And in C, we see old areas of demyelination in the brain that are in a typical pattern for multiple sclerosis. These are periventricular and subcortical white matter hyperintensities. Imaging is also helpful. Again, in the diagnosis, sometimes, of optic neuritis, even during an acute episode of optic neuritis. It’s helpful in determining whether multiple sclerosis is possible or likely, and also helps dictate what additional testing may be needed to more definitively diagnose multiple sclerosis. Optic neuritis is considered a clinical attack, and multiple sclerosis requires, by its definition, a demonstration of dissemination in time and dissemination in space. On the right side of the screen, you’ll see this very complicated graphic that shows the updated 2017 MacDonald criteria for the diagnosis of multiple sclerosis. And I won’t go over all of this, but I do want to point out what would happen if there was evidence of one attack and objective clinical evidence of one additional lesion. Or one lesion. Now, dissemination in space might be demonstrated by two lesions in two different areas of the brain or nervous system. And then sometimes you may find that there’s enhancement of one lesion that you find in the brain and no enhancement of another lesion. And that would be evidence of dissemination in time. However, if the dissemination in time is not present, and otherwise the patient meets dissemination in space criteria, that’s where a lumbar puncture may be helpful to look for oligoclonal bands. So a lumbar puncture may not be helpful in all cases of optic neuritis, but in ones where it would make the diagnosis, or if you’re ruling out some other cause of optic neuritis that may be atypical, then a lumbar puncture may be necessary. But I do not routinely advocate for lumbar punctures in most of my patients with typical optic neuritis. And what about OCT? Or optical coherence tomography? So this is something that has really taken off and is available in many clinical centers. Does it have a role in the diagnosis of optic neuritis? The short answer is: With acute optic neuritis, it’s not very helpful, unless you’re really trying to rule out other causes of optic neuritis and looking for additional clues. However, it is quite sensitive in detecting prior optic neuritis. So, for example, at least three months after an attack, the retinal nerve fiber layer is thinner by at least 9 microns in 73% of optic neuritis eyes. Also, the ganglion cell complex, which consists of the ganglion cell layer, as well as the inner plexiform layer — those layers are thinner by at least 6 microns in almost all patients. In 96% of optic neuritis eyes, when compared with an unaffected eye on the other side. And this top graph shows the unaffected versus affected RNFL thickness. And you see a decrease. And then also the ganglion cell complex also shows a decrease between unaffected and affected. There’s also an interesting effect where the ganglion cell complex thins before the retinal nerve fiber layer thins. And that thinning is detectable in the ganglion cell complex between one and three months after the onset of optic neuritis. So look at this graph here. We see the retinal nerve fiber layer thickness on the upper line. And here is less than four weeks after onset. And you’ll see a decrease in the retinal nerve fiber layer that is continuing even up to nine months out from the time of onset. Whereas the ganglion cell complex, at less than four weeks here, shows a decrease to three months. And then it stays stable from three months on. And so we see the early effects of the damage from optic neuritis on the ganglion cell complex. And this is one of the reasons, when I do OCT, I always make sure that I do a ganglion cell analysis as part of it as well. And there have been times where I have found that there’s a difference that is not detected in the RNFL that I do detect on the ganglion cell complex analysis. And that can be very helpful. If there’s a clinical history that may be consistent with optic neuritis in the past, this can help provide additional evidence that indeed there was some optic neuropathy. It’s not specific for optic neuritis, but does support if there is a clinical history, suggestive of optic neuritis. Other tests that may be helpful are visual evoked potentials. And that is an electrophysiological testing method for visual pathways. I find that it’s not quite as commonly used now as it was in the past. But it may be useful in certain circumstances, and has been used widely in clinical trials. The P100 wave form is the basis for interpretation of this test. We see the wave form here at the bottom right of your screen. And time zero would be the time that the visual stimulus is presented. And this electrode here on the back side of the skull measures the impulses. And this wave form that we see, a positive deflection, is present at the 100 millisecond mark. And that is a normal latency. Patients who have some form of optic neuropathy will have often an increased latency, where the peak of that wave form won’t be at 100 milliseconds, but will be pushed farther down. And so it may be 120 or 130, or even longer. And that is a very sensitive sign for optic neuritis in the past. But it is not very specific. There are other forms of optic neuropathy that will give a similar result. One thing that’s helpful is it often remains abnormal even after recovery from optic neuritis. And in some patients can help provide evidence that someone has had optic neuritis in the past. Now, just to summarize here, what are some features of typical optic neuritis? So we can help distinguish this from atypical optic neuritis. Well, one is that there is pain with eye movements in more than 90% of cases. The optic neuritis is retrobulbar. Meaning that it happens behind the optic nerve head. And for that reason, we won’t see optic disc edema in about 2/3 of cases, and acute funduscopic examination will be normal. There are unilateral symptoms with central vision loss and a relative afferent pupillary defect. Color vision loss out of proportion to the visual acuity. The vision improves substantially over weeks. And we’re going to use that as showing a difference from atypical optic neuritis, which may be more often associated with diseases like neuromyelitis optica spectrum disorder, which we’ll discuss briefly. This figure on the right shows some T2 hyperintensity that is present within the cervical spinal cord, and it is longitudinally extensive, spanning more than three segments of the spinal cord, contiguously, and that is a feature of neuromyelitis optica spectrum disorder. These patients usually have attacks of optic neuritis and myelitis. But they do not have to have it for the diagnosis. One of the reasons for that is that recent research has shown that there is an antibody that is very, very specific for NMO spectrum disorder. And that’s the aquaporin 4 antibody test, which is extremely useful in medical practice. It also helps us realize that neuromyelitis optica spectrum disorder is a distinct entity from multiple sclerosis. They’re definitely not the same disease. And that has great implications for treatment. And in fact, there are even some treatments, such as interferon, that while they are effective for multiple sclerosis, may actually worsen neuromyelitis optica. So how do we diagnose this condition? Well, patients need to have a typical clinical feature of NMO spectrum disorder. That would include optic neuritis, acute myelitis, or another symptom typical of NMOSD. A detection of these antibodies, again, is specific for the condition. And the testing is most helpful when it’s done during an attack. And also before immunotherapy is given. Immunotherapy may decrease the sensitivity of the test. There are different tests out there, and cell-based assays are the most sensitive and specific aquaporin-4 antibody test. The sensitivity is very good. About 76%. But notice the specificity. Almost 100%. 99.9% specificity of aquaporin-4 test in the serum. And that results in very rare false positives. And so you can have a very low threshold to send this test. And in fact, if you want to send it in every case of optic neuritis, that would probably be okay. You can really trust a positive result. And I think to help us understand why it’s so specific, it’s helpful to know how this cell-based assay is performed. The way it’s done is: It doesn’t have to be from the patient. There are human embryonic kidney cells that are harvested. And they are transfected with a plasmid that contains DNA that helps these kidney cells express aquaporin-4 on their surface. And then the cells are introduced to serum from the patient. And if the patient has aquaporin-4 antibodies, they will bind to the antigens that are now expressed on the surface of these cells. And then a fluorescent labeled secondary antibody binds to the primary antibody. And that helps produce a visible signal that helps the technician know that this is a positive test. And so in this case, we’re using real live human cells that are expressing aquaporin-4, and we’re using real antibodies from the patient. And so those features help increase the specificity of this test to nearly 100%. Again, I alluded to some differences in NMO spectrum disorder treatment. And it reminds me of this saying, to first do no harm. And so it’s important for us to identify this disorder and distinguish it from multiple sclerosis, because again, some treatments like interferon β can actually exacerbate neuromyelitis optica spectrum disorder. Furthermore, some of the medications used to treat multiple sclerosis are thought ineffective for NMOSD. So although there are some that are helpful for both, there are some that are harmful or just not helpful for treating NMO spectrum disorder. Now, what other differences are there in treatment? Well, one is what to do during an acute attack or acute exacerbation of neuromyelitis optica spectrum disorder. The treatment is started with 1,000 milligrams daily of IV methylprednisolone, over the course of three to five days. Clinical trials have shown us that plasmapheresis can also be very helpful, and that the sooner the plasmapheresis is done, the better. And so one reasonable approach would be: If the patient is having an inadequate response to steroids within five days, is to then start plasmapheresis. And then maintenance treatment is again, in many cases, quite different from multiple sclerosis. Some of the mainstays of treatment include azathioprine, rituximab, mycophenolate mofetil. A newer treatment is eculizumab. But it increases the risk of meningococcal disease by 1,000 to 2,000-fold. So patients need daily prophylaxis and its use is restricted in the United States. Inebilizumab is a similar treatment. The trial for this medication was stopped early, because it was efficacious. We do need some longer term follow-up, but it is used similarly to rituximab, where there is an infusion given, repeated two weeks later, and then every six months. Satralizumab is an IL-6 receptor blocker, similar percentage, and it’s done with subcutaneous injection every two weeks, three doses, and every four weeks after that. And Tocilizumab, an IL-6 receptor blocker. It was found superior to azathioprine in reducing relapse rate, done by IV infusion every four weeks. This slide I won’t spend too much time on, but this goes over some of the pathophysiology that we know about for NMO spectrum disorder. And the parts of the slide in red refer to different treatments that act on different parts of the pathway of this disease. And I just illustrate that to show that there are many different ways to intervene in this disorder, and so there may be additional ways to treat this, coming forth in the future. And so we’re excited for how much growth there has been in treating this disorder in recent years, and which will certainly continue for the future as well. Another unique feature of NMO spectrum disorder is the distribution of these aquaporin-4 receptors that are very specific for the disease. And this figure on the right shows some of those areas where there are clusters of these receptors. And one thing to note is that there is a relative lack of receptors in the brain parenchyma. And that’s one of the reasons we don’t often see brain lesions very often from NMO spectrum disorder. It’s usually more optic neuritis and myelitis, because of the distribution of receptors in those regions. Also there’s a cluster of receptors near the area postrema, which I’ve illustrated here. Near the floor of the fourth ventricle. And that area has a chemosensitive trigger zone that also makes someone nauseated and vomit easily. So when there’s dysfunction in that area, patients can get what we call area postrema syndrome, where they can get symptoms of intractable nausea and vomiting, and they can even have hiccups from activation or dysfunction of that region. So when you hear intractable hiccups or nausea and vomiting that won’t go away and there’s a history of either optic neuritis or myelitis, that’s very likely gonna be NMO spectrum disorder, and the patient needs to be tested for that, if they haven’t already. Now, what about anti-MOG antibodies? This stands for myelin oligodendrocyte glycoprotein. And this until recently has been found to be associated with another form of optic neuritis that is different from both NMO spectrum disorder associated optic neuritis and idiopathic demyelinating optic neuritis. And this particular glycoprotein is expressed on oligodendrocytes. So again, these are only in the central nervous system. And they’re expressed on the outer lamella of the myelin sheath. And as far as how often we’re seeing anti-MOG optic neuritis, it tends to be about 5% of patients with optic neuritis have anti-MOG antibodies. And by comparison, about 3% of patients with optic neuritis have anti-aquaporin-4 antibodies. So this is very much a minority of optic neuritis. But these are becoming increasingly more common, as they’re recognized. And these are treated much differently. And there’s a lot of potential for us to prevent permanent vision damage, when we identify these disorders. And so we’ll spend some time during this webinar going over those and how to treat and evaluate for those. So first of all, the MRI features of anti-MOG optic neuritis are somewhat unique, and are one of the tools we can use to help distinguish typical optic neuritis from that associated with anti-MOG antibodies. One distinct feature is that anti-MOG optic neuritis often involves a long anterior portion of the optic nerve. So typically an orbital segment. And in addition to that, we also typically see enhancement of the optic nerve sheath. So not just the nerve itself, but the nerve sheath, and the surrounding orbital fat. So this can be similar in appearance to an optic perineuritis. So these patients will have inflammation of the optic nerve and the optic nerve sheath and orbital fat. And there’s often bilateral optic nerve involvement, which is another typical feature of anti-MOG associated optic neuritis. And it’s very important for us to be able to review our own images when possible, because sometimes a radiologist might not know to comment on some of these additional features. And they may just describe that there’s optic neuritis or there’s optic nerve enhancement. But knowing how long that segment is and whether the orbital fat is also involved and whether the sheath is involved as well, those features can really help point you in the direction of anti-MOG optic neuritis. So here is a chart that shows some of the typical characteristics of optic neuritis from these three disorders that we’ve talked about today. So from MS associated optic neuritis, which we hopefully described as typical optic neuritis. And these two other forms would be considered atypical. The aquaporin-4 associated and anti-MOG associated. So what are the differences between these? We’ll go over a few of these. One is with regard to age. Patients with aquaporin-4 antibody disease tend to be a little bit on the older side than MS or MOG-associated optic neuritis. Most of them are more common in females, with the exception of MOG, which is fairly equal male-female predominance. As far as the optic neuritis itself, they’re all painful to some degree. There may be less pain associated with aquaporin-4. Bilateral optic neuritis is a feature of both NMO-associated optic neuritis and MOG. It’s less common in MS-associated optic neuritis. The vision loss tends to be very severe when it’s at its worst in both aquaporin-4 and MOG. And not so much with multiple sclerosis-associated optic neuritis. The risk of recurrence is much higher with NMO and MOG. Steroid dependence is a more common feature with MOG than MS or NMO. The risk of very severe vision loss is also much higher with aquaporin-4-associated disease than the others. And then there tend to be other areas of CNS involvement that I’ll skip for right now. But also the optic nerve enhancement, again, is a distinguishing feature. Aquaporin-4 tends to involve a long piece of the optic nerve and be more posterior. Anti-MOG-associated optic neuritis tends to be a long segment of the nerve and more anterior. And that might also help explain why anti-MOG has more pain associated with it typically than aquaporin-4, based on the research I mentioned earlier, which is that the more posterior portions of the optic nerve when inflamed tend to yield less pain than the more anterior portions of the nerve when they’re inflamed. And optic chiasm involvement is more common in this than in the other conditions. So having a test for these conditions is very helpful when you have a case of optic neuritis. Now let’s go over what we do for the management of anti-MOG optic neuritis. This is a fairly new entity, which has been described, and so we’re still learning a lot about how to optimally treat these patients. For acute attacks, it’s pretty standard and pretty related to the other ways that we treat other optic neuritis entities. And that is with one gram of IV Solu-Medrol over three to five days. And we follow that often with an oral prednisone taper, and sometimes a longer prednisone taper than we may give with other forms of optic neuritis. And part of that is because of the risk of recurrence and of steroid dependence. If the vision loss is severe and we don’t have any significant improvement after one to two weeks, then we might think about other immunotherapies, such as plasma exchange or IVIG. And what we do after that, if someone is positive for anti-MOG antibodies, really depends on how many attacks they have and how well they recovered from each attack. For example, if we have a single attack of MOG associated optic neuritis, and the patient makes a full recovery, at this point, we really don’t think that there is an indication to put the patient on chronic immunosuppressive therapy. And so therefore we just observe. Now, the situation changes if the patient has recurrent attacks, or if there’s steroid dependence, or if they have incomplete recovery after even one of their attacks. And those are signs that this patient would likely benefit from chronic immunotherapy. And so again, the criteria after at least two attacks with incomplete recovery of at least one. And some of those therapies we may consider include rituximab, mycophenolate, azathioprine, or monthly IVIG. We’ve found it’s very effective, or so we think, however, it is associated with an increased cost, compared to some of these other therapies. Now, let’s talk for a moment about anti-MOG antibody testing, the clinical test that’s done. So this is different in some ways from aquaporin-4 antibodies in how sensitive and specific the test is. So anti-MOG antibodies have a lower specificity than aquaporin-4. So you’ll remember that we just mentioned that aquaporin-4 specificity is almost 100%. About 99.9%. And anti-MOG antibody specificity, we think, is probably around 98%. You might think: Well, that’s not a big difference. Maybe 2%? So that’s just about 100%. That sounds great. Well, that does make an important difference, actually, when we’re testing many, many patients, who may or may not have this condition. And it makes an important difference in the positive predictive value of the test. In other words, the probability that a positive test actually represents a truly positive individual. And so the positive predictive value for MOG is about 72%. So that means of the positive tests that you get, if you send them on just about anyone with optic neuritis, about 3/4 of those would be an actual true positive, and about 1/4 would be a false positive. And so that’s — when we think about it in those terms, that’s quite different. However, if you use those same numbers and think about the positive predictive value for aquaporin-4, because it is so much more specific, the positive predictive value is so much higher. 95%. So if you get a positive test, if you send all these cases with optic neuritis, if you get a positive test, 19/20 of those positive tests will be an actual positive. A true positive. So very different numbers. Even though, again, the specificity is so similar. And one other thing to note is that anti-MOG positive patients are sometimes observed without treatment. Remember, if the patient had one clinical attack, and they made a full or nearly full recovery, then we would choose to observe that patient anyway. It’s not — that is not true for aquaporin-4. Whereas if a patient tests positive, they pretty much always need to be on an immunosuppressive regimen to help prevent further attacks. Because those attacks almost always do result in some permanent vision damage. So for these reasons, I typically find that testing of all optic neuritis patients for MOG is not useful. And the reasons for that would be: There can be false positives, and not all MOG patients needed immunosuppression. And so I feel that testing is best reserved for patients with features that suggest MOG optic neuritis. So if they have bilateral optic neuritis, if there are any of the features in that chart that we went over earlier, that show the differences between the different kinds of optic neuritis. And if it seems to fit with MOG or could potentially fit, then yes. We do need to send that test. Because it can still be very important. However, I don’t advocate for indiscriminately sending MOG antibody testing on all patients with optic neuritis. I think you can make a different argument for aquaporin-4, because the test is so specific that if you wanted to test everyone who has optic neuritis for aquaporin-4, that would probably be okay. That really would make a difference if it’s positive and you can really trust that result if it is positive. So, again, what are some of these features that might suggest MOG-associated optic neuritis and might prompt a serum test for the condition? One would be bilateral or recurrent optic neuritis. If the patient has prominent optic disc edema as part of their optic neuritis presentation. Remember, typical optic neuritis, about 2/3 of cases, will not have any disc edema. But it turns out prominent optic disc edema is a typical feature of MOG-associated optic neuritis. If the patient has especially severe vision loss when the vision is at its worst, that also is kind of atypical for optic neuritis, and should prompt testing like this. And then also perineural enhancement on MRI is a feature that we think distinguishes optic neuritis associated with MOG from other forms of optic neuritis, such as that associated with NMO spectrum disorder and with multiple sclerosis. This is especially new data. We’ve had some of the data on the specificity numbers and so forth for MOG — have been relatively recent. In fact, one of these papers that I’ve cited below came out, I think, about a month ago. And so we’re still learning a lot about anti-MOG, and I think it’s helpful for us to know how best to use this tool and to make sure we use it appropriately, so we don’t miss patients that have a disorder that we need to treat, and also that we don’t treat unnecessarily patients who may not have a disorder that we think they did have. So just to summarize: Well, what are these features of atypical optic neuritis? So progressive vision loss, poor visual recovery, painless, hemorrhages or exudates on fundus exam, severe vision loss, and a relapse after steroid withdrawal. So if we leave these kinds of optic neuritis untreated, we may have a poor visual outcome. And then a relapse after steroid withdrawal would need to be treated with a slower withdrawal of steroids and possibly starting an immunosuppressive agent. So that’s also a feature of atypical optic neuritis. And so these atypical features should prompt testing for aquaporin-4 and MOG antibodies. I’ll briefly go over the optic neuritis treatment trial results, to help remind us about some of the evidence-based practice of optic neuritis treatments. In this trial, it included 457 patients with acute optic neuritis. They were randomized to three groups. An IV steroid group, a moderate dose oral steroid group, and an oral placebo group. And they were treated for the durations specified there. And the outcome measures were visual field and contrast sensitivity as the primary outcomes, and then visual acuity and color vision as secondary measures. And these outcomes were measured at various intervals, including six months. And they found that the visual function recovered faster in the IV steroid group than it did in the placebo group. And they also found that oral prednisone alone was associated with an increased risk of optic neuritis recurrence. And for that reason, ever since then, moderate dose oral steroids, like 1 milligram per kilogram per day is not an accepted treatment for acute optic neuritis. And so from this trial and some of the follow-up analyses, we learned that it is acceptable to give or withhold IV steroids in cases of acute optic neuritis that are typical, because the patients will have a similar vision recovery, whether they were treated with IV steroids or not. And later studies showed no improvement in long-term visual outcome with steroids, as I mentioned. Steroids do not affect the long-term risk of the development of MS. And again, there is no role for moderate dose oral steroids alone in the treatment of typical acute demyelinating optic neuritis. Here is a graphic that helps us understand the risk-benefit ratio that needs to be considered when we’re talking about treating a patient with typical optic neuritis. So these things on the left are features that may suggest a higher potential for benefit from treatment. Such as acute onset. White matter lesions on brain MRI. If they have significant pain, significant vision impairment, or any features of atypical optic neuritis. There might be more potential for adverse reactions if someone has poorly controlled diabetes, a history of adverse reactions to steroids, or other potential for significant side effects from steroids. And so when do we treat the patient with optic neuritis? Well, we treat them if the vision is sufficiently impaired to justify the treatment risks. And so again, the steroids, they hasten the recovery of the vision, but do not result in any permanent vision preservation. And so let’s go on to: How can we treat this, if we do decide to treat, and we want to decide how exactly to treat them? There was an interesting trial done not too long ago that looked at the effect of treating optic neuritis with a bioequivalent oral dose. The way the optic neuritis treatment trial was designed was to use 1 milligram per kilogram oral dosing. So in most patients, that might be 60 to 80 milligrams a day of prednisone. But what if we used a dose that was much higher of oral steroids that was more similar to the IV dose? What would happen then? And that’s what these authors did in this trial. They found 55 optic neuritis treatment patients within 14 days of symptom onset. They randomized them to three days of 1 gram IV methylprednisolone daily, versus three days of the bioequivalent prednisone dose, which was 1250 milligrams daily with no oral taper. And what they found was that there was no difference between the two groups in the primary endpoint of P100 latency on VEP at 6 months, or the secondary endpoints of high and low contrast visual acuity at 1 and 6 months. So this was a small trial, but still provided some evidence that maybe higher dose oral steroids may be an acceptable treatment option for patients with optic neuritis, with acute optic neuritis. And so ever since this trial, I’ve kind of rethought how I treat some patients with acute optic neuritis. One of the major benefits of this, of the oral steroid treatment, is the ease of administration and the cost savings. So this can be given as 25 50 milligram pills. And yes, that’s a lot of pills. But I often recommend that patients blend them into a smoothie. And if they do that, they can drink the smoothie and get all their prednisone in there, and then they don’t have to mess around with going to an infusion center, or getting admitted to the hospital, or whatever is needed for IV steroids. And so we still have no evidence that IV or PO treatment of typical optic neuritis in these doses makes any impact on the long-term vision outcomes. Similarly, in oral steroid taper — do we need to do that or not with optic neuritis? Well, it was part of the optic neuritis treatment trial. So some people did it just because it was the way the trial was designed. However, we know it has no effect on short or long-term outcomes in MS. And some clinicians include the taper after a megadose steroid treatment and others don’t. I think there are pros and cons to each approach. The pros are that this is the way the optic neuritis treatment trial was designed. So we know what the effects are from that trial. And it could be beneficial. We don’t have any trials that compared optic neuritis treatment with or without the taper. So it’s still possible it could be helpful. However, we know it doesn’t have any effect on outcomes in multiple sclerosis. And also, there’s some extra cost and potential for side effects in susceptible patients. So those might be some of the cons. So it’s really up to us to decide whether an oral steroid taper is right for our patients. And then, in closing, I’ll just mention some things about pediatric optic neuritis, which is slightly different from adult optic neuritis in some ways. One is that vision loss is more often bilateral and more often severe than in adults. Kids more often present with funduscopic abnormalities, such as retinal exudates or disc edema. They also recover faster and have a higher percentage of secondary causes. In other words, not always idiopathic, than in adults. And the treatment is a little different. Kids are often treated with high dose IV steroids, and then followed by a longer steroid taper, orally, and some people think that there may be an increased risk of recurrence for these kids. And that has been the justification for a longer oral taper. So, in other words, pediatric optic neuritis is more typically atypical. And, for example, kids can certainly get disorders like anti-MOG optic neuritis as well. So it’s worth keeping those in mind. Okay. So that does it with the webinar portion. And now I’m gonna spend some time going through some of the questions in the chat. Okay. So here in a remote area of Indonesia, we only have a CT scan. Would it help in any way, and what can we see in the CT scan? So great question. CT scans are not as helpful for the diagnosis of optic neuritis unless you’re trying to rule something else out. So CT scans are great for looking at bones and looking at blood. So if there’s some concern there could be some traumatic event like a hematoma, or a fracture that’s affecting the optic nerve, or something like that, then yes. It’s very helpful. However, if you’re pretty sure clinically that someone has optic neuritis, the CT scan is probably not gonna be as helpful. And in that case, you’re really relying on your clinical acumen to diagnose optic neuritis. And that’s okay. Because optic neuritis is a clinical diagnosis. Okay. And someone says: Sorry that we do not have fancy equipment to diagnose and advanced drugs to treat. So please make a suggestion of using steroid from acute condition until maintenance. You can still rely on some of the clinical features. Again, that chart that I showed, of the different features for each of the conditions. MS optic neuritis, NMO optic neuritis, and MOG optic neuritis are all different, clinically. And so you can still make an estimate based on that, and try your best to treat in those conditions. And you can use steroids for a lot of these patients. And steroids are an immunosuppressive medication. The problem is they have side effects. And so that’s one of the issues. You can still stabilize someone and do much good for them by using steroids, until they can be on an immunosuppressive regimen, if that’s possible in the future. All right. Can COVID cause optic neuritis? There are COVID cases that have been associated with optic neuritis. And some of that may be due to an activation of the immune system that happens as part of COVID. So similar in some ways to other postinfectious inflammatory conditions. And so yes, it can be associated that way. It really wouldn’t have a different or specific treatment, though, other than what you would normally — how you would normally treat someone with COVID. As far as — can COVID vaccination cause optic neuritis? Well… There are cases where they have been associated. It’s a little hard to sort out still, you know, would these patients have gotten optic neuritis anyway, or was there… Were these patients already primed for optic neuritis, and then this was an additional trigger? It’s really hard to sort that out. So I think the jury is still out on that. And so we’ll have to see how that turns out. I don’t believe that it’s a unique cause for optic neuritis. Although I do think it can maybe be a trigger in some cases. I think that’s possible. Okay. In your experience, and in literature, what are the effects of pregnancy and postpartum period on optic neuritis? Well, we know that if we consider optic neuritis from the perspective of multiple sclerosis, we know that multiple sclerosis is often less active during pregnancy. And so we see that in MS-related optic neuritis as well. That there’s a decreased incidence in those patients. I’m not aware of data, though, that shows what happens in patients who have MOG or NMO spectrum disorder-associated optic neuritis. I’m not sure about the effects of pregnancy in those. I would have to do a literature review to see if anyone has published anything on that recently. Same thing. Management of optic neuritis during pregnancy. The management itself is typically the same. The difference would be with — certainly with immunosuppressants, that are longer term, longer acting ones, those are gonna be ones you don’t want to use. Often steroids are okay in pregnancy. And so you would just want to clear that with the patient’s obstetrician to make sure there weren’t any specific contraindications in that patient. Okay. And then there was a question about the use of OCT in optic neuritis. Again, OCT is not very helpful in acute optic neuritis, unless you’re looking to rule out some other potential cause of optic neuritis, I suppose. And even that it won’t be very good at. Where it is useful in optic neuritis is telling you if someone may have had optic neuritis in the past. At least a month ago. Remember, the ganglion cell complex can show thinning between one and three months after optic neuritis, whereas the nerve fiber layer thinning that happens after optic neuritis takes a little bit longer and may take three or more months. So again, it’s helpful for looking for previous optic neuritis rather than acute optic neuritis. Papilledema and disc edema are the same. Where to use the terminology appropriately? So papilledema and disc edema are actually different terms. Papilledema is the term we use to describe optic disc edema that is from raised intracranial pressure alone. Optic disc edema is used to describe any form of optic disc edema. Whether it’s papilledema, whether it’s disc edema from optic neuritis. Any of those can be called disc edema. But papilledema is very specific only to edema from raised intracranial pressure. Is NMO spectrum disease curable? As far as we know now, it is not curable. The duration for treatment is also variable. It’s often years long. As far as how many years, that’s gonna depend on a lot of variables, such as how many attacks the patient has, how debilitating the attacks are, and the risk that the patient is willing to assume. And the side effects of the medication. So there’s a lot that really goes into that, and it’s gonna be different for every patient. And as far as titration of the medications, there’s a pretty standard dosing for a lot of these medications. And so I don’t worry too much about a titration for any of the medications. Okay. Will low vision assessment be helpful to patients suffering from optic neuritis? So… Potentially. One of the things that would not be a good idea to do is to have a low vision assessment early on. Because, again, most patients with optic neuritis get much better. So greater than 90% will have a visual acuity of 20/40 or better after their typical episode of optic neuritis. So I would reserve that for patients who did not recover well and may have very severe vision loss, especially if it’s in both eyes. That’s really where low vision would be helpful. So how could we define the inadequate response to methylprednisolone in NMO spectrum disorder? So that’s kind of a subjective call. So certainly if there’s no improvement, that would qualify. Or there’s worsening. That would qualify. If there’s a little bit of improvement and the patient still has vision loss that is so bad that it’s gonna interfere with their daily functioning or their ability to do their job, then I would say that would be time to do plasma exchange. If it’s fairly mild and they’re still able to get by and maybe they don’t want to accept the risks of treatment, or the costs of treatment with plasma exchange, then it might be reasonable to withhold it in that kind of a case. But yeah. It’s a judgment call. There’s not a specific way to define what an inadequate response is. That’s a good point. For the acute exacerbation, is it all right to break down the daily 1 gram methylprednisolone to 250 milligrams QID for a smaller built patient? Oh, absolutely. In fact, that’s the way the optic neuritis treatment trial was designed. Was with 250 milligrams four times daily. Now, of course, that increases the burden on nurses or other health care professionals that administer the medication. So there’s that component to it. But otherwise, no. There’s not a problem to doing it that way. How can you assess inadequate response to steroid in the acute phase? I think we just answered that a couple of questions ago. The association of diabetes with optic neuritis. I’m not aware of any specific link between diabetes and optic neuritis, in terms of it being a specific risk factor. How long do you need to continue azathioprine for maintenance? What dose do you prefer? I don’t really have a preferred dose. As far as how long to continue it for maintenance, again, just as I mentioned with the other immunosuppressive therapies, it’s gonna depend on so many different variables. How severe the vision loss was, how many recurrences they’ve had. You know, how they’re tolerating the medication. What kind of risks they’re willing to take. How long they’ve been on the medication. There’s just so many variables. It’s hard to know how long you need to be on it. It’s reasonable for it to be at least a few years, I would say. At that point, if they’re not having any flares and they’re willing to come off the medication, it might be reasonable to try it. I’ve seen treating optic neuropathy and optic neuritis with neurobion or vitamin B complex. Can this treatment work? We haven’t had any randomized controlled trials that have looked at treatment of optic neuritis with vitamin B complex. We know that vitamin B complex plays an important role in vision, because we do find patients with deficiencies who have vision loss. However, the pathophysiology in those cases is significantly different from optic neuritis. So I’m not certain that that would work. However, the risk also for vitamin B complex supplementation is very low. It’s really just about — the only risk is the cost of it. So if a patient wanted to try that, I think that would be very reasonable to do. However, I would not strongly recommend it. Or give hope that this would be a cure or a way to effectively treat optic neuritis. All right. What is the role of CT and MRI to diagnose optic neuritis? So MRI is very important, and its role is really in helping someone know whether they have multiple sclerosis, and also what their risk in the future of multiple sclerosis would be. That’s for typical optic neuritis. For atypical optic neuritis, you can look for signs of either NMO spectrum disorder or anti-MOG-associated optic neuritis, which I went over earlier in the webinar. And as I also mentioned in a previous question, the role of CT scan is very limited in patients with optic neuritis. Will it be enough to request cervical and thoracic MRI only in cases of NMO to check transverse myelitis for patients with financial constraints? So for patients with financial constraints, I try to be judicious in the way… In how much testing I order for those patients. So certainly if they have signs of myelopathy on exam — so that would include things like increased reflexes, if there’s some weakness or sensory changes in the limbs that is not otherwise accounted for, then yes, I would want to scan those patients. However, if we’re worried about NMO, I think it’s a lot easier and cheaper to send the aquaporin-4 antibody test. If it’s positive, you’re gonna treat the patient no matter what. No matter whether they had transverse myelitis or not in the past. In that case, you can still get without a cervical or thoracic spine MRI. And that may help the patients save costs if that’s a concern. I don’t do that indiscriminately in all patients. And the role of acetazolamide. It has a role in elevated intracranial pressure and papilledema associated with that. However, I’m not aware of any role of acetazolamide being effective in optic neuritis. What explains the pain difference in the optic nerve segments? You know, I don’t know, exactly. We know that there must be differences in the innervation, so the trigeminal system innervates that area, so the area of the orbits and the face, and those areas. So there’s something different about the innervation in those. But exactly what it is, and kind of the details of that, I’m not aware of. So that’s kind of an interesting clinical question. Do you have a situation in a patient after COVID optic neuritis? We talked a little bit about that earlier. I think there can be an association between COVID and optic neuritis. The same way you can get a postinfectious inflammatory condition, transiently, after certain infections. And how did you manage them? The same way you would any other case of optic neuritis and also the same way you would manage COVID, typically. Is there any explanation for why does the optic neuritis recur with oral prednisone alone? That’s a very good question. We never did find an explanation for that with the optic neuritis treatment trial. And in fact, other trials have also looked at that, and did not find an increase in the recurrence of optic neuritis after treatment with moderate dose oral steroid. So it may have been a spurious result. However, it was a very rigorously well designed trial. And bottom line is we know that dose of steroids is just not helpful. So we really just don’t use that in the treatment of acute optic neuritis. And again, megadose oral steroids is different. But for 1 milligram per kilogram dosing, that, we know, is not effective for optic neuritis. Okay. Should we give methylprednisolone for every episode of optic neuritis? For example, if we have two episodes per year, and have that to do with MRI results? No. You do not need to treat every episode of optic neuritis. So if we go back to the slide where I showed the balance that showed the risks and benefits of doing treatment — of treating optic neuritis. And especially if it’s typical optic neuritis, you don’t change the final visual outcome by treating. So you have to weigh: How bad is the vision loss? How much pain do they have? How debilitating is this for them? What are the risks for having complications from the treatment? And so all of those things will go into the decision whether to treat. No, you do not need to feel compelled to treat every episode of optic neuritis that’s typical. Atypical cases, I would treat for every case. And that’s because there’s a much higher risk, we think, of permanent vision damage. We think there may be some benefit to treating, in terms of longer term visual outcomes in atypical cases. We don’t have data to definitively confirm that, but it sounds like that’s probably the case. Does high dose steroid cause peptic ulcer or discomfort? Well, it can if it’s prolonged. So if we use it in some of these cases for three days… And so I haven’t run into any cases where we’ve developed peptic ulcers from three days of steroids. But if it’s a longer course, weeks or longer, then yes, that’s possible. Are megadose oral steroids well tolerated by your patients? Yes, they are. I’ve had a number of patients with it, and all of them have been happy with it, I would say. Common adverse effects — I would say mood irritability. Sleep changes. Transient elevations in blood sugars. I think those would be some of the common side effects I’ve seen in those patients. Can it be divided into four doses per day, or should it just be one megadose? I think you could do four doses per day. I worry a little bit about patient compliance when they do that. Just making it more difficult for them. However, if a patient requested that and was very reliable, I think that would be a very reasonable way to treat as well. Thank you. I appreciate your appreciation. Thank you. For those patients that give you… That you give high dose oral steroids, do you get patients with gastrointestinal symptoms? So I think we already answered that. So not in the short course. But if it’s a longer course of steroids, then yes. Should you have prophylaxis for these patients? Yes, if it’s a longer course. COVID-19 infection and the flare of MS? So I’m not a multiple sclerosis specialist. So I don’t know about flares of MS. I know at least in terms of optic neuritis, there have been associated cases, but not a dramatic number. And so we’re not treating those any different than we treat other cases of optic neuritis at this point. Is there any difference between giving 1 gram versus 250 milligrams four times daily — no. There’s no difference. Whatever is best for you. There has been some argument about the role of flu vaccines. Any word on that issue? Again, vaccines that cause an inflammatory… Having an inflammatory response as kind of a side effect — those can increase the incidence of optic neuritis. So that’s possible. Still, in terms of, for most patients, vaccines are very effective, and again, patients with those kinds of optic neuritis tend to do very well and recover very well. So I would not discourage patients typically from getting flu vaccines. How do you proceed in a diabetic patient? You’ve got to be very careful with blood sugar monitoring if you’re treating with steroids. Any particular MRI scan? MRI brain and orbit protocol would be what I would recommend. 1.5 Tesla or 3 Tesla? 1.5 Tesla is adequate for most cases. If you’re looking for fine details, 3 Tesla would be nice and would be better if you have that option. But 1.5 is perfectly acceptable for most cases. How can we treat patients where we have limited types of steroids and no other drugs? So… You can treat the patients with steroids, and then use some kind of oral steroid taper afterwards. And see if they recur. If they recur, you may need to use a lower dose of kind of a maintenance dose of oral steroids. As a substitution for other immunosuppressants. Again, patients tend to have side effects from that. So it’s not ideal. And it’s probably not as effective as other immunosuppressant therapies, when needed. But if that’s all you have, then steroids are better than nothing for a lot of those patients. I had a case post-MS optic neuritis that developed an attack 20 days after having COVID-19. Yeah, so… Those can happen. Is there any benefit in prescribing antioxidants to patients with optic neuritis? I’m not aware of any specific benefit of that practice. No. What is the preferred immunosuppressant first choice for recurrent NMO spectrum disorder or anti-MOG associated recurrence? I went over that in the webinar. So you can go back to those slides and see some of the medications I listed. There isn’t one specific medication that we know is better for these, for everyone. It’s gonna depend on side effect profile, cost, patient preference. There’s a lot of things that go into it. So there’s a few different medications that are helpful. So for NMO spectrum disorder, I know rituximab is commonly used. And azathioprine is commonly used. And for anti-MOG, we also have some patients on azathioprine, some on rituximab, some on IVIG. That’s a more expensive treatment, but seems to be more effective than the others. So there’s a lot of nuance that goes into all those. How would you treat papillitis? Does it depend on the cause? Exactly. It depends on the cause. Papillitis is really — I consider it just kind of optic disc edema. So again, many, many causes of that. It’s gonna depend on the underlying cause. Let’s see. RP trigger optic neuritis? I’m not sure what that means. Are there triggers for optic neuritis, maybe? There are some risk factors for it. Which I went over in the webinar. So you can find those there toward the beginning. In terms of side effects, oral prednisone has a higher side effect on multiple organ. Can we still use it as treatment for optic neuritis? Yes, if you use the megadose. Moderate dose, 1 milligram per kilogram per day is not effective and might actually be harmful. So only megadoses, which would be 1250 milligrams daily for three days may be as effective as IV steroids, as far as we know so far. So other than the megadose, how long should the patient consume the prednisone? So we have minimal side effects. Well, you do it in acute optic neuritis for three to five days. And so after that, you don’t need to use steroids unless there’s recurrence. In which case you kind of go over that again. What is the common cause of optic neuritis in children? So children have different causes. So they can have systemic inflammatory disorders that can lead to optic neuritis. They’re also more likely to get ADEM, which is acute disseminated encephalomyelitis, which can be associated with optic neuritis, and is similar to multiple sclerosis. But unlike multiple sclerosis, it’s monophasic. Whereas multiple sclerosis is usually relapsing/remitting. Should we check blood tests and CT on first visit? CT I don’t think is very helpful in the management of optic neuritis. Blood tests — that will depend on the patient’s clinical presentation. As far as you should test for things like anti-MOG or NMO antibodies. Should we treat with steroid first? If it seems like the patient is fairly severely affected, then yes. So that was something we went over in the webinar as well. As far as what would be the indications to treat someone. If IV interferon has to be used in treatment, what doses and duration is it used? So I don’t use interferon. So that’s a treatment for multiple sclerosis. I would leave that up to a multiple sclerosis specialist. Why oral prednisone therapy alone is contraindicated in the treatment of optic neuritis? Well, it’s the… (audio drop) contraindicated because in the optic neuritis treatment trial, it was associated with an increased risk of optic neuritis recurrence. So that’s the reason. How do you treat patients with severe vision loss from an attack of optic neuritis when you see them months after the initial attack? What exams do you request for those kinds of patients? I don’t offer treatment if it’s months later. And that’s because I think the patient will have very little chance of me helping them by the treatment. And they still have all the risks of the treatment. And so that doesn’t make sense to me, to try to treat that. Unless it has worsened. If it’s a new recurrence or something, that’s different. But if it’s the same attack and it happened months ago and they’re improving, the best thing is to just observe at that point. As far as what exams I request, I don’t have any specific exams that I request. Yeah. For that. What is the ratio and incidence of MS and NMO spectrum disorder? I’m not sure what ratio you’re referring to there. Sorry about that. What will be the treatment modality for patients with uncontrolled diabetes? It’s still steroids. You just have to be very careful with it. Monitor blood sugars carefully. Sometimes patients are in the inpatient setting, if they need really intensive blood glucose monitoring while they’re on steroids, and so those would be some options. That way, they can get insulin as needed and just be watched carefully. For pediatric optic neuritis, what is the dose for IV steroids? So I would have to look that up. I don’t see children typically in my clinical practice. So that’s something I would have to defer to someone who does pediatrics. Treatment of toxic optic neuritis? That would be removal of the offending agent. If there’s a toxic optic neuropathy. And that’s not usually an optic neuritis, typically. It’s usually… I would distinguish that as different from optic neuritis. Can IV methylprednisolone be started before the MRI scan in cases where a delay is expected? Absolutely. You don’t need to wait for the MRI. If you think clinically it’s optic neuritis, you can treat. Does ESR play a role in diagnosing optic neuritis? Not really. It can look for some evidence of another condition, but I don’t find it helpful, usually. Treatment for acute optic neuritis in diabetic cases. We already answered that. Is colorblindness a permanent symptom in a patient who had optic neuritis? Yeah, there can be some permanent color vision damage. Although patients do improve a lot. Yeah, there can be some permanent damage. In Nigeria, I think methylprednisolone is sometimes difficult to find and some patients cannot afford it. Can we treat with oral prednisolone alone? Yes, megadoses can be helpful. What to do when the patient has uncontrolled diabetes? We answered that already. What are the IV doses of methylprednisolone to be used in infants? We already mentioned that. What is the alternative treatment for patients with optic neuritis and active PTB? I don’t know what PTB is. I’m not sure what that acronym is. Does retinitis pigmentosa trigger optic neuritis? No, it doesn’t. Any role for IV steroids in metachromatic leukodystrophy? That would be out of the scope of this webinar today. How do you differentiate new attacks from previous? OCT can be really helpful in seeing if there’s prior damage. If there’s optic disc pallor on examination, that’s a sign of prior damage. Also visually evoked potentials can help you know if there was prior damage, although that won’t distinguish a new attack from a previous attack. And really the clinical history is probably gonna be the best. I’m gonna just talk to the patient and ask them and see when their symptoms started. Is it worsening or getting better? Just all those typical clinical history questions. Any potential side effects from empirical treatment of IV steroids in clinical optic neuritis without imaging diagnosis? One thing I worry about is in cases that are atypical, whether you could be dealing with infection. I had at least one case where someone was diagnosed with syphilis and ended up worsening because someone treated with oral steroids before I got to see the patient, and they got worse. Probably in part because of the steroids, as well as untreated syphilis. Otherwise, I don’t worry about any potential side effects being really harmful. In the optic neuritis treatment trial, there was rare pancreatitis that could happen. But that’s really rare. I don’t think I’ve ever had a patient have that from IV steroids. What is the alternative treatment for patients with optic neuritis and active pulmonary tuberculosis. So that’s a little bit different. Optic neuritis if it’s from the tuberculosis, then treatment of tuberculosis is gonna be the way to address that. So most of what we’re talking about today would not apply in that case. Is giant cell arteritis commonly associated with optic neuritis? No, they are separate entities. Giant cell arteritis causes an ischemic disorder of the optic nerve. Optic neuritis is inflammatory, primarily directed toward the nerve and the myelin and not the vessels. In patients with optic disc edema can you make any differential diagnosis from the appearance of the optic disc? Great question. It turns out: No, you can’t just by looking at the disc figure out what kind of optic neuropathy someone has in most cases. One exception to that might be if someone has segmental optic nerve swelling that is altitudinal. That’s very suggestive of non-arteritic anterior ischemic optic neuropathy. But in terms of optic neuritis, no, there’s not a way to tell the different kinds just by looking at the disc. For pulmonary tuberculosis treatment caused optic neuropathy, will steroids also play a role? I’m not sure that that’s been studied rigorously. So certainly treatment should be directed at the tuberculosis itself. If there was no contraindication, you could consider steroids. But I’m not sure that we have data to tell us what the right answer is in that case. So that is a tough clinical challenge. Okay. And that takes care of our questions, I think. Thank you, everyone, for joining today. And I wish you the best of luck out there with treating your optic neuritis cases.