 Our guest speaker today is Dr. Steve Felden. He's going to be giving a talk this afternoon about the idiopathic intracranial hypertension treatment trial and give us an update on the treatment of that disease, which of course is one of the most common diseases we see in our neuroclinic. But before that, we had a live patient upstairs with thyroid eye disease that's going to be presented by our fellow, Dr. Anastasia Newfeld. And then we have an in absentia patient with neurofibromatosis type 2 who's really had a rough time. Tara, are you going to be presenting that patient? Okay, awesome. So let's start off by having Anastasia present the thyroid eye patient that was upstairs, then Dr. Felden will comment, and then I'll have Tara come up, present the NF2 patient, and Dr. Felden will comment, and then we'll kick off the rest of the day. Thank you, Dr. Katz. For those of you who were last night at the Dr. Mandike's dinner, we got to see the vast expertise that Dr. Felden has on thyroid eye disease. So this is a really nice way to put that expertise into practical terms for you today. And I just wanted to thank the live patient we had today who is present in the room, and we just really appreciate you being able to come and spend this time with us and share your story. So my job really is to kind of give you the context of the history so that the discussion is productive for all of us. So we have a 62-year-old woman who originally presented in July of 2014 with some systemic symptoms of thyroid eye disease, specifically some shortness of breath and a bit of tremor. And of course, thyroid workup was initiated and she was found to have a TSH that was significantly low and an elevated T4. She was then referred to endocrinology, who then decided to proceed with radioactive iodine therapy and after the therapy she was placed on, Synthroid. Now we move on and fast forward a few, almost a year and a half, and we then see the patient in ophthalmology. And initially she presented some intermittent dyplopia and some eye injection. The eye was firmed to retropulsion on examination. She did not have proptosis at that time and definitely no optic neuropathy. At that time we treated the dry eye symptoms and the irritated eye symptoms with a humidifier, some head elevation and lubrication, and she was prescribed Volteran systemically and Catorlac drops. Endocrinology saw her again in March of 2016 and noted that she had Pritibial Myxidema and they were wondering whether this was kind of erythemundendosum versus Pritibial Myxidema, but they treated our patient with prednisone and tapered that off. This is the visit in April where we started to be concerned about the thyroid eye disease and its manifestations. The visual acuity had dropped from normal to 2070 on the right and 2025 on the left. And as you can see the pressures in primary gaze and up gaze are very typical for those that are seen in thyroid eye disease patients with elevation in up gaze. And we first initially, for the first time actually saw an RAPD on the right. There's just some data here to suggest that there are indeed features of thyroid eye disease and, concerningly, color vision on the right had dropped significantly to zero to tennisy horror plates. Critical flicker fusion frequency was also asymmetric, again indicating the right optic neuropathy and there was some mild pallor of the optic nerve on the right. This is the motility here and you can see that there is an esotropia and right hypertropia that's seen in primary gaze and, again, very typically up gaze restriction in both eyes. So I think this is probably the most important part of the talk and this is the visual fields representing the significant optic neuropathy that's developed. So the first field is from February of 2016, just a kind of initial presentation to us, which is really reassuring, but as you can see, the fields begin to progress. And in May of 2016, especially on the left, you see the visual acuity drop to 20 over 250 and you're starting to notice that there is some visual field deficit noted on the left as well. This is an MRI that exemplifies the features. Those are both axion coronal T1 post-Gatellinium fat suppression sequences and these are meant to show you the significant enlargement of the extracula muscles with compression on the optic nerve and the same is seen on the other side as well. So just to go back to the fields there, how did we address this and how did we treat this? In April, after the first note of the right compressive optic neuropathy, we treated the patient with methyl pernizolone, 1 gram IV, once a week for three weeks and she required an orbital decompression which involved the medial and lateral walls as well as some lid surgeries at that time. So the story goes on and we note that later in May we still have continued visual field progression as you can see both right and left are involved and further on, again, we see further progression of the compressive optic neuropathy bilaterally and the middle field there is done in June of 2016. So something clearly needed to be done at that point again and on July 1st the patient underwent again a repeat bilateral medial and apical orbital bony decompression as well as partial ethmoidectomy at the time. In addition to that, retrobalbal steroid injection was given in both orbits. In July of 2016, in addition to the surgery, radiation was administered to the orbits and the examination in August of 2016 showed actually improved visual acuity in both eyes. The pressures were still within the normal range. There was an RAPD noted on the left, color vision had improved and critical flicker fusion frequency had improved as well. The cover testing did show is a tropia of 35 in primary gaze which is again increased from the previous measurements. Now bilateral optic nerves had some temporal pallor. So that is kind of a quick run through the history. I have some suggestions for discussion but I thought maybe we get Dr. Felden to come up and discuss the case from his perspective, offer his suggestions and we can go to the discussion questions if needed. I'm delighted to be here and it's nice to see a lot of old friends and meet some new ones. And I hope that some of you were present last night and talked a lot about potential new therapies and some of the frustrations with our current therapies related to thyroid eye disease. One of the things that's most interesting is that the incidence of this severe disease is actually going down. And whether that's due to people no longer smoking or whether it's due to some other environmental factor or perhaps we're just better treating hyperthyroidism, we're detecting it earlier and I think that that may also be a factor. The philosophy about thyroid eye disease is our myriad but the treatments are pretty stereotyped. And I think that in patients who are not otherwise at risk giving radioactive iodine to treat the thyroid condition I think is perfectly reasonable and this tends to be sort of a local phenomenon. So when I was in Los Angeles, you know, 90% of my hyperthyroid patients were treated with radioactive iodine now that in Rochester maybe five percent are treated with radioactive iodine. So there's a lot of variation which means that nobody knows exactly what the best treatment is. But I think it's pretty well established that patients that have radioactive iodine do have a slightly increased risk of developing eye findings. I think that that's been established in class one type studies, prospective studies. And also that patients who have thyroid eye disease as mild tends to get worse when they get their radioactive iodine. So there's been I think a pretty much a consensus that patients who have risk factors should be on low dose corticosteroids for perhaps a week before and perhaps two or three weeks after the time they get radioactive iodine, 20, 30 milligrams of prednisone per day and certainly not enough to get all the long term side effects and not high enough dose to have short term side effects. And I think that that's a good practice and I certainly recommend it to my patients. So the question here is, well, were there any risk factors? So our patient today had a history, remote history of smoking in the 70s so it's really hard to say that that is a big risk factor. The biggest risk factor is probably age. And so when you see patients that are in their 20s and 30s, which is the peak for hyperthyroidism, I think that they're nonsmokers, I think you really have no risk factors. But once you start to get into the 50s, then I think that the risk of developing eye disease does go up and that there may be a little stronger case even if somebody has no eye findings at all for prophylaxis with corticosteroids, low dose corticosteroids during that time. So that's one thing. Radiotherapy versus for compressive optic neuropathy versus using decompression. So last night I mentioned that when I first started in practice in the late 1970s, we had an armamentarium that consisted of high dose corticosteroids, orbital radiation, and orbital decompression. Today we have the same exact things. So we have made, in terms of progress, a lot of new potential treatments coming on the market but none that have really displaced the mainstays of therapy. There's a lot of controversy about the role of orbital radiation and there's a very thoughtful group that basically any patient, as soon as they start to develop any kinds of inflammation or periorbital inflammation, they're going to go and get radiated. And then there's another group that radiates a patient maybe once every three years when they have terrible optic neuropathy. So there's no consensus. The prospective clinical trials related to orbital radiation for thyroid eye disease. The one study that came out of the Mayo Clinic showed no effect but on the other hand they were sort of taking all comers and it was unclear what degree of inflammation where they were. And that's the problem we have with all of our patients in terms of trying to do studies, no two thyroid patients are the same. And so their end points are all different and where they are and their disease is different and what we call severe thyroid eye disease like our patient today has is not, we say well that's active disease. Well it's not active. It's progressing in terms of symptoms and signs. But the activity is probably long past. There's probably not acute inflammatory responses going on. What we're seeing is scarring and the effects of increased tissue within the eye socket. The pressure effects that I talked about a little bit last night. As well as the fact that the orbital fibroblasts which are activated are integral disease and either turn into fat tissue or into scar tissue. And then elaborate hyaluronin which brings in a lot of fluid which raises the tissue pressure and produces the meschemia. So as far as radiation the only real contraindications that I see to using orbital radiation is a patient's diabetic or has other severe vascular disease. Those patients do very poorly with radiation and I wouldn't recommend it. But in the absence of that I think that this is a perfectly reasonable thing to do. The question as well should you use the radiation and steroids first or should you have done them after decompression? I would have done it the way that you've done it here. Decompression works to alleviate optic neuropathy somewhere around 90% of the time especially in terms of color vision and visual acuity. A little bit less so in related visual field about 70%. So that's better than what you get with radiation and steroids which have to be given together. And also if patients are already toxic from steroids you're prolonging their steroids by giving them radiation as opposed to doing decompression where oftentimes you can take them off their steroids. So in terms of what the new options are I did publish one patient who after who had a course very similar to our patient today who progressed and progressed and progressed two decompressions and finally I put her on Celebrex which I talked about a little bit yesterday because it's been shown to really inhibit the reactive response, the inflammatory and immune response in thyroid disease and actually that patient did better on Celebrex and recovered vision whereas on steroids was losing vision. So there's one other thing. We don't have post-operative CTs or MRIs here so it's hard to know what the first and second orbital decompressions do and I use a different technique so which bony walls are decompressed may be slightly different but in the patients where I found that they initially got better after decompression and then got worse again what I actually found is that the posterior wall of the maxillary sinus was kinking the nerve as it was coming into the orbit and so you have the anterior, the inferior rectus say well look like it's a hammock, it falls down but it's being held up by the posterior wall and so it's kinked at that point and when I've gone in and taken out the posterior wall of the maxillary sinus and just then the optic neuropathy got better and so I think that it's very important for our patient today to really go back and study those scans and make sure that you haven't produced a secondary cause for the optic neuropathy as opposed to just having not enough overall decompression. It can be very focal and 10 minutes worth of tipping away a little bit of bone and I tend to use a transantral route which gives me access to everything but the roof and that would be the other option for this patient. This is who I've had who have failed on three wall decompression. Dr. Nassiger, a neurosurgeon, popularized the Nassiger procedure and it is a transcranial orbital decompression and those patients that I've had that have been recalcitrant like this with this kind of optic neuropathy they have done well with transcranial or decompression and that's the experience of the Mayo Clinic group as well. So I think that you don't want to wait too long if you're going to consider this route but getting the entire orbital roof removed all the way back and unroofing a portion all the way back to the canal is something that might be considered in this particular patient. Well obviously I can go on and on and on but I think that this is a very concerning and not that infrequent issue that we deal with. Our patient is still on 30 milligrams of prednisone per day and she is you know that's now you're producing a secondary disease it'd be nice to find some sort of acute intervention where you could get off the steroids or at least back on to the non-steroidal anti-inflammatories. Any questions? In terms of the order of doing the decompression or the radiation some of our people have said that the tissue in the orbit is just different after radiation treatment and when you're going to be doing a decompression it just doesn't behave the same way has that been your experience? Well I believe so I think that's sort of true in some cases the I think the problem is when you get really elevated tissue pressure you get fat necrosis and that's what you're really seeing is you're seeing the effects of chronic high tissue pressure and you're getting fat necrosis and then the it doesn't you get this sort of gritty fatty fibrous tissue stuff whether it's the radiation that enhances that or not I really don't know but you know I prefer surgery before radiation there are many people who do just the opposite the real question is how many people didn't need to come to surgery if they had had orbital radiation and the answer is actually none and the reason is that all those patients end up with orbital decompression anyway the difference is instead of having it acutely and under you know all sorts of stress it's done electively in order to start the restoration process. Any other questions? Yes. I just wanted to add that the benefit that you get from radiation really is not immediate as a matter of fact you can really kind of stir things up a bit so you have to be prepared for there to be more information with the acute radiation and then hope that over the next six months the things really quiet down from the radiation so if you're in an acute vision loss type setting I think that what Steve said is very apt that there's going to be a decompression happening. And so I absolutely the other thing is that the experience that the Europeans have had with IV pulse therapy weekly therapy is very much different from what we have here in the United States where we don't they were talking about complete resolution reversal of changes all this stuff we just don't see it and in the high dose that they were using the 8 grams there was an unacceptable incidence of death from high dose methyl prednisolone I mean it's not a lethal disease but there was a lethal treatment that was advocated now with the lower doses and I the recommendations about six grams but the patients getting worse while you're watching them that's not it personally I prefer oral steroids if they're not going to get better within two weeks on a hundred milligrams of prednisone then I can manage them and taper them they're off to the operating room and then we'll see what we get after that so there there's no one way to manage these our patient here today has been managed beautifully I think that there's still more that can be done