 Good morning, everyone. We're going to go ahead and get started. I'm Strava Gunta, one of the ophthalmology interns, has started this year. I'm going to be introducing our speakers this morning. To start off with, we have Christian Mitrovic. She's a neurosurgery resident, fourth year, and she's going to be presenting on bilateral optic neuritis. All right, so like she said, I'm Kristen, and I'll be talking about bilateral optic neuritis. So the case is a 37-year-old woman. She presented with two weeks of worsening vision in her left eye. She had no significant past medical history, family history, just notable for her cousin, and a great aunt that were diagnosed with multiple sclerosis. She had no family history migraines, and then she had no tobacco, alcohol, or drug use. Her symptom progression is as follows. She started having a daily migraine for about two weeks, and then she developed left eye blurriness of her vision and then noted pain with eye movement as well. That lasted for about one week, and then the symptoms progressed. She woke up, and the vision was completely dark in that left eye. This prompted further evaluation. She went to an outside ER, had an MRI brain that was reportedly read as normal. She then presented to RER, and her exam was notable for a BMI of 39. Her right eye visual acuity was 2030. Left eye was light perception with projection. She had red desaturation bilaterally. Pupils were reactive, and she had bilateral optic disswelling. The remainder of her neurologic exam was normal. Her ophthalmologic exam, which was done one day later after she had received one dose of methylprednisolone, showed a visual acuity of in the right eye, 2020, left eye, 2500. Pupils were notable for a 0.9 log efferent pupillary defect in the left eye. And then her color testing, left eye was essentially absent, and right eye was slightly reduced. Flickrfusion was asymmetric with the left eye being greatly reduced. Her eye movements were normal, and slit lip exam was also normal. Her visual fields are as follows. So in the left eye, she's got an enlarged central scatoma. And then in the right eye, she's got sort of this enlarged seaco-central scatoma as long as some peripheral defects as well. Her fundus pictures are shown here. So in the right eye, you can see swelling mostly superially, nasally, and inferiorly. And the left eye swelling is most notable for superiorly and then inferiorly as well. Her OCT was also consistent with the findings on the fundoscopic exam. She had in the right eye swelling superially, inferiorly, or left eye more notable superiorly. So her workup at this time, she had serum labs, showed a normal CVC, CMP was normal. She had negative studies for ACE, aquaporn4 antibodies, RPR, SSA, SSB. Vitamin D was a little bit low at 25. Hemoglobin A1C normal, 5.4. B12 was on the low end of normal, but OK. Her lumbar puncture showed an opening pressure of 27, but she was in the fetal position, not legs outstretched. And then her CSF studies, initial ones were normal with two whites, four reds, glucose of 57, protein 41. And the negative CSF studies included ACE that was repeated on the CSF, IgG index, oligoclonal bands, RPR, and VZV PCR. She had imaging with an MRI brain, MRI C spine, and MRI T spine. And I've got two of her MRI brain images here. So on the left, we've got a fat sap flare. And you can see bilateral hyperintensities in the optic nerves. And then on the right is a T1 post-contrast. And she's got bilateral optic nerve enhancement, pretty extensive enhancement. So all of this was consistent with optic neuritis. So bilateral optic neuritis, about 10% of patients who develop optic neuritis, it's actually bilateral symptoms, either simultaneously occurring or in rapid succession, so within sort of a two-week period of each other. It's more commonly bilateral in children under the age of 12, and that typically follows a viral syndrome and is not often associated with multiple sclerosis. It's also more common to be bilateral in Asian and Black South African patients. This is from an article by Voss. He kind of proposes a clinical approach to going through optic neuritis. But essentially, if you have someone that you suspect optic neuritis, the first thing to figure out is whether the symptoms are sort of typical or atypical. And I'll go over sort of the atypical stuff, red flags to watch for. If it's typical, you're going down the standard route of MRI, figuring out if there are lesions to lead you down the MS route and whether you should be starting to disease modifying drugs. If it's atypical symptoms, then you're going to be considering sort of other pathologies that I'll discuss in a bit. So typical signs of optic neuritis, most of us know them, but the age is going to be somewhere between 12 and 50. It's usually acute or subacute vision loss that progresses over a couple of days, up to two weeks, but not much longer than that. It's often unilateral, reduced color vision and contrast vision. They often have pain with movement or pain around the eye. It's normal or swollen optic disc. And then the macula and peripheral retina should be normal. And then they should spontaneously improve within a two to three week period with no deterioration after steroid withdrawal. Some of the red flags are atypical signs that should prompt sort of you to think of other processes. So bilateral symptoms are on this list. But also, if the age is falling outside that typical range, they're less than 12 or if they're in the older population, over 50. Not that over 50 is old, but a little bit older. And then if the vision loss is very sudden or if it's prolonged, so more than two weeks of vision loss. If it's very severe with no light perception, and then if they don't have associated pain, they have a history of neoplasia. And then if you see symptoms of systemic disease, or obviously if they've been diagnosed with one of these diseases in the past. Also, if you see severe optic disc edema or hemorrhage, if they don't recover or if they deteriorate after steroid withdrawal. So lab tests, everyone generally should get sort of basic CRP, CVC, CMP, ANA, and vitamin B12. And then the additional test is just an abbreviated list. But essentially you're looking at rheumatologic diseases, markers of inflammation, vasculitis. And a lot of that's gonna be driven by your history and the questions that you're probing deeper. So some of the evaluation, obviously, you're gonna wanna get an MRI, often if the findings, if they have a raging tumor that's compressing, that will lead you down that path. If they have in the C-spinal, longitudinally extensive transverse myelitis, you're thinking NMO and going down that road. If they have recent vaccination, think of post-vaccinal optic neuritis, a viral prodrome, you can think of post-viral optic neuritis, or ADEM if they've got white lesions, so acute disseminated encephalomyelitis. And then if they have systemic symptoms, that's the big thing to ask about. Arthralgias, myalgias, hematuria, hemoptysis, chronic fever, rash, facial swelling, mucosal ulcerations, things that are gonna guide you more towards the rheumatologic pathway or even thinking of some off-beat cancers. And then your ophthalmologic exam is important. If they have uveitis, that can often be a sign of a systemic process, so it might guide you that direction. Diseases to consider, I just broke them down by category, broad category here, but connective tissue disorders and vasculitis. This is kind of your, in my mind it's the biggest things that I think of with these patients, but sarcoidosis, you can have an isolated neurosarcoidosis, I saw a case report of that, without systemic signs and optic neuritis was the presenting symptom. Lupus, chogrens, antiphospholipin antibody syndrome, weginers, giant cell arduitis and viscets. Autoimmune and perineoplastic, the perineoplastic antibodies that have been associated more with optic neuritis are anti-CRMP5 and then MAG antibodies. And then some of the autoimmune stuff, NMO is considered autoimmune along with ADEM. And then neoplasm-wise, sorry, acute disseminated encephalomyelitis, yeah. Sorry for that kind of. Neoplasm, so carcinomatosis, or if you've got a direct compressive neuropathy that could mimic optic neuritis as well. Inflammatory conditions, so post-infection or post-vaccination, and then some infections that have been noted to cause it are Lyme disease, which is rare in general and exceptionally rare here because we don't have Lyme disease. And then syphilis, TB also pretty rare, but can occur, and then viral optic neuritis. Most commonly it ends up being herpes zoster. So further evaluation, so if it truly is just an isolated bilateral optic neuritis, you should expect to see improvement in several weeks and the improvement is similar to what was seen in the optic neuritis treatment trial with unilateral disease. If there's no improvement or if the patient relapses, which again, it's similar to unilateral disease with bilateral, you should be reconsidering the systemic processes. Sort of going back to the drawing board, rechecking labs, considering a repeat MRI, and then consider a skin biopsy looking for vasculitis. Clinical outcomes in bilateral, so Dayla Cruz at all did a retrospective review of 15 patients that had bilateral optic neuritis from 2000 to 2004. They excluded patients who had a diagnosis of MS or myelopathy, known systemic disorders if they were on meds that were associated with optic neuropathy or if they had neoplasm. All the patients received standard treatment with IV methanol prednisolone course followed by oral prednisone, and then they looked at neuroexams and ophthalmologic exams at baseline and then six or 12 months. In all the patients, except for one, recovery was good to excellent, which again, is similar to what was seen in the optic neuritis treatment trial. And then one point that I wanted to make about the optic neuritis treatment trial is this question of bilateral disease. So of the patients that were enrolled, actually 67% ended up having some abnormality in their testing in the unaffected eye. These deficits, when they repeated testing down the road improved, so it suggests that many of them actually had bilateral disease initially, although the MRI findings did not directly correlate with the clinical disease. So fewer had MRI changes, although they had some clinical change. Getting back to our patient. So she was treated with one gram of IV methanol prednisolone daily for five days followed by an oral prednisone taper, which she's actually currently on. She initially improved her left eye color vision, but then it returned to the previous kind of level of her deficit on day three of steroids. She's continued to have a headache and right now, as of this week, she is continuing to follow up with all her providers and considering the next step, whether or not we should pursue plasmapheresis and further work up. And that is about it. This is a picture from Mount Raymond up in Big Cottonwood Canyon, but any questions? Patients at risk initially at the end of that study, do you think there's any progress? Yeah, so it's the same. If you end up excluding sort of the other systemic stuff and going down that typical pathway, it's all the same as the opticonorrhagous treatment trial studies that they found. So if you find white matter lesions on the initial MRI, then you're gonna be, there's a high risk of developing MS, basically. So it's the same, the outcomes are the same in terms of development of MS, but the bilateral presence in the beginning should just prompt you to look for those other stuff because it's just a little atypical. That's what it comes in. In this particular case, for instance, MS is extremely low because she didn't have any of her leaders other than her officers and she had negative all over the whole band. And that combination argues pretty strongly that one of the grossest is the cause and it's pretty strongly against having a significant risk of MS in the future. Yeah. So how do you account for the MRI being normal? Was that an issue? Not getting the right scan? Great question. Not interpreting it appropriately. How do you? So it's gonna be the latter of those two. So her scan, let's just go back to it. It's so symmetric. So she came in with essentially the scan. We have her outside in the gym. And it's, you know, if you glance at this and you're trained to look, okay, one side compared to the other, it looks so symmetric. But it's ragingly enhancing. But if you're looking for kind of that clue on the other side. It was an interpretation issue. Exactly. She's scanning the one body of the R at her. She absolutely on that. The day that she went to the outside VR, which was just the day she came, before she came here, it was absolutely positive. It looked like this. Very good thing. This may actually be her outside imaging. I forget if I pulled in the one that she had here. I think it is her outside imaging. I think it is her outside imaging. Normally, on a post-contrast study, the optic mirrors are barely visible in the organs. And so this is, yeah, it's ragingly enhancing. The other thing that I want to bring up imaging-wise is that they're now doing these fat-saturated flare. So the flare images are the most ones that you use to look for white matter of lesions in the rest of the brain. White matter of lesions in the rest of the brain. And you can never see the optic mirrors because the mirrors are surrounded by fat and that wasn't disappeared on the flare. Now they can do fat-saturated flare. And so in a patient who maybe for some reason can't get contrast, like maybe they're pregnant or something, or they have rainbow problems, fat-saturated flare is going to be much, much more sensitive for optic nerve ventilation than a regular T2 or a sperm or other sorts of things, much higher sensitivity. And they are incorporating now into their routine studies of optic nerve disorders. And her, I mean, if you look at just her sadidal flare, you don't see anything in the optic nerves. This is kind of the most hyper-intense lesions I've ever seen in the optic nerves. So it just goes to show that fat-saturated makes a big difference. And then one other interesting thing about our imaging, I didn't include it here, but typically you don't see any diffusion-weighted changes, but she actually had bilateral diffusion-weighted changes in her optic nerves that you could see, which I had just never seen before. Ah, that's true, that's horrible. It's fair, like, that's true.