 Alright, thanks Mike. The last speaker today is Nigel Stipa, who is a medical student coming from Long Island. And he will be talking to us about OCT and the optic nerve. Okay, can you hear me? So again, I'm going to be talking about the role of optic nerve OCT in the evaluation of central retinal vein occlusion. But my talk is going to be a little different from the other two talks as I'm going to be talking about the usefulness of the optic nerve OCT in light of an interesting case. So let's get started. Sorry about that. Alright, so the patient is a 64 year old Caucasian female with a history of type 2 diabetes and malignant right breast melanoma, complaining of blurry vision for about one week and left sided headaches for a month that ranged from 2 to 9 out of 10 in severity and was worse in the evening. It seemed to have an insidious onset as she noticed that she had some blurring of her vision and she covered her right eye and kind of noticed that she had very, very, very little vision in the left eye. And she reports no other symptoms, no systemic signs, no fever, no jaw claudication, no myalgias and no other ocular symptoms, no foreign body sensation, no pain of the eye, just the headaches on the left side and the blurring of vision. Now given her recent history of malignant melanoma, it's important to note her timeline. Eleven months prior to presentation she had surgical resection for a right breast melanoma and was found to have positive sentinel lymph nodes and consequently interferon therapy was initiated. Three months prior to her presentation the interferon therapy was discontinued, secondary to severe weight loss and alopecia and at that time a PET scan was negative for metastatic disease. Just to give a little more history she has no significant ocular history. She allergic to codeine, she takes metformin and a multivitamin. Her father had type 2 diabetes and diet 68 due to an MI, mother had breast cancer and diet at 86 and there's no significant ocular family history. And of note in the social history she has been smoking one pack per day for the past 35 years. So on exam her visual acuity in her right eye was 2020 and hand motion on the left. There was also an APD present on the left eye. The pressure in both eyes bilaterally was normal. Her color vision was undetectable OS and the visual field was unattainable. Her right eye was normal. Both eyes had full motility and the slit limp exam was within normal limits on both sides except for the posterior exam. So the dilated funnest exam on the left showed significant discodema, some scattered hemorrhages throughout the posterior pole while the right eye was normal and I left out the stage because as a teaching point quickly I like to go through the frisson scale which grades discodema. So I've listed a couple characteristics for each stage but I bolded kind of the important points to quickly determine the stage of discodema. So stage one is characterized by obscuration of the nasal border of the disc and you can see that in this picture that nasal border is obscured while you maintain the superior temporal and inferior border of the disc. Stage two is similar in that you have an obscuration of all the borders. Stage three you have an obscuration of one or more segments of a major blood vessel as it's leaving the disc and that's kind of important to identifying the stage. You can see the vessels on the disc but as you know it right here that there's an obscuration of one of the major vessels as it leaves. Stage four is characterized by total obscuration of the discs, of the vessels on the disc margin and near total obscuration on the disc surface. And then five is simply just total obscuration of vessels on the disc surface. So now that we've gone through the scaling, let's look at the fondest photos of our patient and so how would you classify that? So it's stage five because all the vessels are obscured and as you can see the discodema put together with the hemorrhages scattered all over the posterior pole that this patient is presenting with a CRBO. Now given the patient's age and the fact that she has diabetes, it's not surprising that she may present with a CRBO. Other factors that can contribute include hypertension or a hyperquaggable state, hyperlipidemia, inflammatory conditions or a tumor. So her age is significant but her diabetes, maletus was actually pretty well controlled. So in light of that and her OCT, this is the OCT of the optic nerve head of her right eye and these two images below is the OCT of the optic nerve head of her left eye and you can see the significant discodema in both images but what else do you notice in the lower two images? Of note, if you look at the RPE in the normal right eye you can see how it's kind of deflected downward in the normal position, in a V shape that's pointed away from the vitreous here. Whereas in the left eye the RPE is kind of deflected towards the vitreous at least on this side and you can kind of see it here in this other image and Patrick Sibony, the chairman at our home institution and neuro-ophthalmologist has recognized this kind of pattern in patients that have intracranial hypertension and so he hypothesized that the intracranial hypertension can be manifest as a deflection of the sclera that can be assumed to also be seen as a deflection of the RPE so he hypothesized that you have this translaminar pressure gradient in combination with causing a deformation of the sclera and that's a deformation of the RPE and so Dr. Sibony utilized geometric morphometrics and SDOCT to compare the peripapillary retinal pigment epithelium Brooks membrane shape in eyes with papillodema, eyes with anterior ischemic optic neuropathy and normal eyes. Here again you see a normal eye, the normal position of the RPE Brooks membrane and so he looked at 30 normals, 20 eyes with AION and 25 with papillodema and intracranial hypertension. So as I said he utilized a technique called geometric morphometrics. It's an analytical technique to quantify and statistically analyze the shape of biological forms. So he used 20 equidistant semi-landmarks and digitized them onto the OCT images of the RPE and Brooks membrane spanning 200 microns on each side of the neural canal opening and data analysis was performed using standard geometric morphometric techniques including a generalized least squares across just superimposition, which in layman terms kind of superimposes the multiple images. A principal component analysis which can determine how close or how different the shape is and thin plate spleen is kind of a smoothing program. And so he found a statistically significant difference between eyes with intracranial hypertension and papillodema and eyes with AION and the normal eyes. So the peripapillary retinal pigment epithelium of normals and eyes with AION displayed that characteristic V shape directed away from the vitreous whereas the peripapillary RPE of eyes with papillodema have an inverted U shape inward toward the vitreous which is what our patient displayed. And of significance is that there was no significant difference between normals and AION and this is critical. So what that means is that the discadema alone is not enough to explain the change in shape of the RPE. And then in select cases of papillodema the pre- and post-treatment OCTs demonstrated a change from that inverted U shape associated with intracranial hypertension to the characteristic V shape associated with a normal pressure. So A shows the points, the semi- landmarks that were superimposed on the OCT from the three groups. So the blue represents the points from the patients with papillodema. The black represents the points of the normal eyes and the red represents the points of the eyes with AION. And so you can always start to see that there's this one shape for the blue which is the eyes of papillodema and the other normal shape for the normal eyes and the eyes of AION. And then B just takes the means for each group and then C draws a line through each point so you can kind of see the two different RPE shapes. The blue one associated with papillodema and intracranial hypertension, the red and black are the normal and the AION associated with no intracranial hypertension and hence the normal shape. And then here's one of the patients with papillodema. We have a pretreatment and a post-treatment OCT. And so you can see the deflection of the RPE and the eye and both eyes with intracranial hypertension papillodema. And then two days later it's not quite back to normal but you can see two days after an LP with the normalization of the pressure you can see a flattening of the RPE that's getting closer and closer to that normal V shape that we saw. So he went one step further and he looked at the shape of the peripapilly RPE in eyes with presumed optic nerve shape meningiomas versus normal eyes using a very, very similar technique. Now they're denoted presumed based on clinical data and MRI data. So he looked at 30 normals and 10 patients. So there were 11 eyes with presumed optic nerve shape meningioma because one of the patients actually had bilateral involvement interestingly. And he performed a similar shape analysis using the SDOCT and the geometric morphometric techniques. And he also looked at other variables including tumor size, proximity to the globe, age, and the thickness of the retinal nerve fiber layer. And he found very similar results that there was indeed a statistically significant difference in the shape of the RPE between nearly all eyes with presumed optic nerve shape meningioma and normals. Now the shape was statistically different but in this case the shape ranged from that inverted U to kind of a flattening of the regular V shape of the RPE. And that makes sense because there was, you know, the tumor sizes were different and the proximity to the globe was different. And they found that the greatest deformation associated with meningioma was abutting the globe but they also saw deformation among patients with the tumors remote from the globe. However, patient 11 displayed no apparent deformation but this kind of makes sense because that patient had the smallest tumor and that tumor was the furthest from the globe. So they found a correlation of 0.75 regarding the size and proximity of the tumor to the globe. So they concluded that similarly to the eyes of papillodema causing that deformation of the RPE that a tumor of the optic nerve sheath can kind of cause a local increase in pressure and cause a pressure gradient, a transformer pressure gradient that can cause deformation of the sclera and thus a deformation of the RPE. So if we go back to our patient, MRI of the brain and the orbits revealed a six millimeter lesion in the right frontal lobe and extensive tumor involving the left optic nerve sheath that was hyper intense on T1. The top differential is a brain met in addition to meningioma of the optic nerve sheath. However, meningiomas of the optic nerve sheath typically are iso intense on T1. So the fact that it was hyper intense on T1 is concerning. And in addition, this CSF cytology was normal. So here we go. So on T1, you can see the hyper intensity of this optic nerve sheath tumor kind of going along the length of it. And you don't really see it as well on the T2 or the STIR. But you can also see it here on the T1 with contrast. So optic nerve biopsy and fenestration was performed. And very interestingly, the surgical pathology revealed malignant melanoma with immunohistochemical standing MA-RT1 and HM45, which was consistent with the patient's previous diagnosis of malignant melanoma of her right breast. And this patient was going to get cyberknife due to the single met in the frontal lobe. However, a follow-up MRI revealed multiple met since she subsequently received whole brain radiation. Then six months later, after her whole brain radiation she was no light perception OS, although the hemorrhages and the venous stasis had resolved. So just a couple final thoughts. So this is her OCT before, which I showed you earlier, and then after the optic nerve fenestration. So this correlates with Dr. Sibony's theories about the deflection of the RPE as a representation of a trans-laminar pressure. And it's either caused by intracranial hypertension and papillodema, or as seen in the optic nerve shape in angiomas or in this patient, the metastatic melanoma to the optic nerve that you can actually see, see the deflection regardless of whether it's a local pressure or intracranial pressure. And then with the release of that pressure through optic nerve fenestration, you see a return to the normal V-shape that's directed away from the vitreous. And so this case exemplifies the utility of recognizing the peripapillary RPE deformation in the detection of infiltrating optic nerve sheath tumors presenting with CRBO and or discodema, and especially in a patient with a history of malignant disease. And that's the thing, they haven't really looked at that yet. And as I kind of talked about, when they studied with the presumed optic nerve sheath in angiomas, there was a gradient depending on the size of the tumor and where the tumor was in reference to the globe. Because the one tumor was missed. So there really isn't, I think, perhaps more studies need to be done to kind of find a threshold. But especially in a patient with a CRBO with stage five discodema in addition to any kind of risks including a history of cancer, I think, warrants, they have not, that's very interesting. That's a very interesting thought. Yeah, I know you looked at the anterior skin of optic neuropathy, and that showed that has this significant discodema as well, but no pressure. And so the AION had the regular RPE look. But I'm not sure, I don't think he's looked at optic neuritis specifically. Okay, I'll let him know. They all had discodema. Yeah, that was one of the criteria. I think they only included, at least in that study, they included the patients with discodema. I don't know if they saw ones without it or not, I'm not sure. I was involved in that study, per se. That sounds amazing. Thank you. Oh, okay, nice to meet you.