 Okay, good morning. We're going to get started with our GreenRound presentation. And this morning, we have Ron Hobbs presenting. He's one of our Retina Fellows. He's the first-year fellow, and he's been so great to work with from a resident perspective. It's been really awesome. And I went to the mid-year forum recently and talked to some of the Oklahoma residents, and they shared with me that Ron was actually the chief chief last year, which he would be too humble to tell us, but apparently he was elected the chief of the chiefs when he was a resident. So it's a pleasure to hear from him today, and he's going to talk about what to present. It is so hard to pick. Talk a little bit about pick today. Thanks for having me. Wanted to post this picture. I love this picture. I think our own Jim from here took it. He was explaining it to me where he takes an underexposed and over-exposed picture and combines them with it on a tripod. One of the things that I was just blown away with when I came and interviewed here for fellowship was just the beauty of this building. It's a gorgeous building. It's a gorgeous backdrop. I think everyone who comes here is first blown away by that and then amazed by it once they get to see the great things that are happening inside the building, of course. I love that picture. And then quickly, financial disclosures. I have none, but this is where most of my finances go here. It's probably the Halloween costumes. So the patient is a 27-year-old female. One week before presenting to us, she said she started seeing shimmering lights in her left eye. And with that, she also described this spot kind of in the center of her vision in her left eye. She states that during that week that spot increased in size and she felt like the vision around the area of the spot was also dim in her central vision. She really denied any pain or erythema or other changes with the eye. Past medical history, she has a history of asthma and she has a history of migraines. In fact, the evening before we saw her, she was seen in the emergency department complaining of severe headache. She said she had tunnel vision at that point, dizziness, and she had difficulty speaking. So she was seen by neurology there. She had an MRI, which did show one small lesion in the right frontal lobe. It was questionable over whether or not that might be a small demyelinating lesion. She was given the migraine cocktail and her symptoms improved. So she was diagnosed at that point with a complicated migraine and sent home to follow up with us the next day. She had no surgical history. She does have a sister with keratoconus and she herself has mild myopia. She's a minus one and a quarter in each eye. As far as her review of systems goes, she about two weeks prior had an upper respiratory infection. And then she states that over the past month, she's been having a big increase in her migraines. She states she used to have about two to three migraines a month. And over the past month, it's been almost daily with a couple of times a week having nausea, vomiting, light sensitivity. Medications, she uses an albuterol inhaler as needed in Yasmin. And she says she was recently finished oral steroids for her upper respiratory infection given to her by her PCP. And then no known drug allergies. So when she presented to us visions good in both eyes, just 2015 in her right eye, 2020 in her left eye. And the remainder of her external exam is normal in both eyes. Her anterior segment examination also is within normal limits. There's no inflammation noted in either eye. And on her dilated funoscopic exam on her first appearance, there was questionable old rare cells in the anterior vitreous. Here's a picture of her right eye. It's kind of small, so I'll point out. There's a questionable little hypopigmented spot there that you see. Maybe another one right down here. Not very glaring when you first look at her right eye. Here's her left eye. Much more obvious here. You see a couple hypopigmented spots here, here, here. One up here if you look real close. So here they both are together. Obviously more involvement of the left eye. And this is the eye she's having her symptoms in. Here's infrared images. Infrared images are good at showing some subtle pigmentary changes that we might have a hard time seeing in color at this little amp. But these images of the right eye, you can see a little more impressive. Just a couple little pigmentary changes in the right eye. And then in the left eye, a similar picture with a couple more lesions that weren't quite so obvious on the color photos. And then funosodil fluorescence. Before describing this, I'll just run through it real quickly. Because I know this is kind of newer images that we're using. But the way I think of funosodil fluorescence is underneath the retina in the RP we have lipofluscin that deposits as a product of breakdown of the photoreceptor cells. So you'll get kind of this lipofluscin gives you a baseline hyper-autoflorescence that you see. And that's kind of this light gray, this baseline hyper-autoflorescence. So things that don't have lipofluscin will have hypoautoflorescence such as the optic nerve, your arteries and veins. And just the way the phobia is set up, you don't get hyper-autoflorescence there because of the way the pigment is absorbed. So anytime you see hypoautoflorescence other than that, such as these spots here, those would be areas where you have RPE loss. So you have dead RPE cells, RP that's very sick is what that's showing. And then areas where you have increased hypoautoflorescence, such as right here, you see this lighter band here, is areas where you have probably sick RPE around where you have an increase in the lipofluscin deposit. So the RP isn't working as well to clear that. You get increased lipofluscin buildup and you'll get hyper-autoflorescence. So just after that brief review on this right eye now, on this we see maybe even a couple other spots that we didn't see on the color photos at all and on the infrared. And on the left eye, same picture. You start looking around and you see other little spots that show up here, which are demonstrating then these hypoautoflorescence spots are demonstrating sick RPE or dead RPE. And then surrounding those areas you have this hyper-autoflorescence which is showing us accumulation of lipofluscin. Here's the OCT from the right eye on an initial presentation and it looks great. There's really no abnormalities seen there. And here's the left eye. You'll notice just some subtle changes here at the level of the RPE. There's a little indentation with some loss of the ISOS, border junction just above that. And again, you can see that here right through the central cut through the phobia. Red-free images again show what we've seen. And here's the fluorescent angiogram of the right eye. So this is the early, 45 seconds, 3 minutes, almost 7 minutes. You see these early hyper-autoflorescence spots. They don't expand at all at 3 minutes or at 7 minutes. So that's very consistent with window defects there. Again, dead or lost RPE. And we're seeing right through it to the fluorescein underneath in the choroid. And then the left eye, early photos here and here and then 3 minutes here and 6 minutes here. And again, it just shows more spots than we're clinically evident looking at the patient. No leakage on these areas of hyper-florescence. They seem to stay the same throughout. And then ICG on the right eye. If you look carefully, you can see these couple hypo-florescence spots centrally. We term ICG kind of as we break it into early, mid-frames and late-frames. So early being 0 to 4 minutes, it's different than fluorescein angiogram. Mid being more of 4 to 8 to 10 minutes. And late-frames kind of that after 8 to 10 minutes. So in this case, this patient has in early these hyper-florescence spots that you see in the mid-frames and stays there in the late-frame. And then the left eye, similar picture, just more pronounced, more hyper-florescence spots centrally. Patient had a multifocal ERG performed. So just quickly review that this is the normal reference down here. The blue ones, you expect to see how the A, B wave. Pretty good in the right eye. In the left eye, if you look close, you have some subtle changes here. But overall, that's a pretty good multifocal ERG. Not a very impressive loss. But there's a little loss of the wave pattern centrally in the left eye corresponding with fluorescein angiogram. And then here's the cone of this. Again, these are the normals you would expect down here in the bottom four. On this right eye here, you can see it's not the nice cone peak you would expect to see. That's more consistent with these spots like this with she probably lost fixation for a little bit. It would give you appearance like this, not so much that she has lost there. And the left eye, actually the eye that we see more involvement in looks better. And both eyes there look pretty stable. So not much change seen there. So differential diagnosis at this point, just for the sake of being very complete, I put a lot of things on here, but punctate interchloridopathy would be right on the top of our list given a presentation, the lack of vitreous cell that we're seeing. Multifocal chlorideitis and panubiasis would look very similar. You would expect to see vitreous cell. But there is some debate over people if these are just as variations of the same disease process and maybe this is burnt out or early, we're not seeing that vitreous yet. Of course histoplasmosis can look very similar without cell as well. Amudes would be considered on there as well. Of course you'd expect it to be unilateral, but she is a young myopic female. 25% of them can be bilateral, so it's worth considering. Retinal pigment epithelitis or Krill's disease would be another consideration. It can give you these creamy, small lesions. Again a little more common in male, two-thirds in male, but you can have a third of the patients presenting as females, and it could be an early indication of that. And a few sub-retinal fibrosis would be bilateral, and this could be early changes seen with that. Inflammatory on a systemic level then, sarcoid, and we're always talking like just about anything, so I always wanted to consider maybe an early inflammatory disease to fit the right profile for a tenu or for inflammatory bowel or riders, maybe early changes seen with that. Infectious, I think the herpes also can look like many things. Post-viral, the Epstein-Barr virus, you can see changes like this that usually then resolve. These are thought to be more of immune complexes that deposit in the cord that you might see after a viral illness like Epstein-Barr or cytomegalovirus or coxacvirus. And then septic coriditis, you know, especially given her history of recently being on systemic steroids, perhaps she has some septic amylide that were sent there, syphilis tuberculosis. And then the masquerade ones, I don't think it really looks like any of these, but for the sake of just completing this, I think you always should remember trauma when you see pigmentary changes in the retina. Myopia can cause those, although she's pretty mild, and then retinal dystrophy is early can give you pigmentary changes. So her initial laboratory workup consisted of an ESR, an RPR, ACE, PPD, they were all normal. And of course, in the evening before she was seen, she had this MRI ring. And as I mentioned before, it had a small lesion, which was a questionable demyelinating lesion in the right frontal lobe. So we called this a PIC, and just briefly to review PIC. It's an inflammatory disorder. It was first, it's only 29 years old, recently celebrated its 29th birthday after being described by Dr. Watski in 1984. In his initial cohort, he described 12 patients. And the youngest was 16, the oldest was 40, and that's really stuck, you know. Most people still kind of stick to those numbers. You see it in between those age groups. 90% of the patients who you'll see with PIC are women. And in fact, a recent study just showed that 97% of them are white women. So it's really a disease of white women. And most will have a history of moderate myopia with the history of a, without a history, sorry, of a preceding illness. And then it's considered to be less common than its cousin, multifocal corditis and pan-uviitis, which presents very similarly, but with inflammation seen. The incidence is estimated at roughly 100 to 200 in the U.S. This is, it's a big guess. This came from a study recently in Iowa. They went back and looked over 16 years worth of patients that they had who presented with PIC and they had 16 in 16 years. So they consider considering themselves the tertiary referral center for the state of Iowa. They said, let's consider we get every new patient for the state of Iowa who presents with PIC and our population is 2.6 million. And it's one out of 2.6 million per year. And they just then carried that out to the country in which case they said, well, you get about 150 a year then in the country. Clinical features, the three main complaints you'll see are blurred vision, central or paracentral scatoma and photopsias. Usually just in one eye, even though they have involvement in both eyes, usually they're just noticing it in the eye that's mostly involved. The blurred vision, of course, would be due to clustering of lesions in the macular. They can't present even with the crudal neovascular membrane. Even though the more prominent science seen on visual field is enlargement of the blind spot, most people don't notice that. So they're coming in with central or paracentral scatomas just like our patient and photopsias just like our patient. In addition, they can get these serous retinal detachments surrounding these PIC lesions as well. What you typically see are these yellow-white lesions. They'll have indistinct borders. They're at the level of the RPE or the coroid, usually pretty small, around 200 microns. And located almost exclusively in the posterior pole. It's very rare to see them in the mid periphery. In fact, if you see very many in the mid periphery at all, you should question your diagnosis. No vitritus or at least very little vitritus can be associated with it. Bilateral and 80% and usually asymmetric. At the initial presentation, often you'll see a hyperemic optic nerve. And then as these progress, you'll be left with this atrophic scar with the halo surrounding the scar. And, you know, what I put down here is these crudal neovascular membranes are associated in 30 to 75%. Most people will say around 40 to 50%, but there's just so many different numbers that have been found in different studies. So test what you expect to see. On our patient, it was quite a classic presentation. Early hyper fluorescence. And then you can have variable leakage or staining associated with that, depending on the presence of neovascular membranes. And then often you'll see many more lesions than you can see on exam with it. I thought our left eye was a great example that you could see a lot of lesions there that weren't obvious on the color photos. On ICG, you'll get these hypo fluorescent lesions, which is thought to correspond with hypo perfusion of the choroid and mostly involving the small choroidal vessels. And then on the OCT, we're really just starting to get a picture of this, and I'll talk about one study that they try to describe the classic changes in PIC, but you get kind of this homogenous thickening of these coriorentinal lesions, and you'll get deposits of a hyperreflective material between the RPE and, sorry, underneath the RPE and Brooks membrane. And it can also cause changes in the outer retinal layer. And then you can have defects in Brooks membrane and loss, classically you'll see loss of the ISOS junction during the active phase, and then that seems to reappear as the active phase calms down. Amza grid can be helpful as well, showing some scutomas, and then visual field. Most often you'll see enlargement of the blind spot or temporal visual field loss surrounding the adopted nerve, but you can also get central and paracentral scutomas. So the etiology of PIC remains unclear. It has been linked to HLADR2, like multiple sclerosis and some other eye diseases as well, but it's a pretty weak link. Some people have questioned if it's just a variant of multifocal coriorentitis and panubiitis, since they're very similar, maybe just a little different presentation of the same disease, and some question if it's just associated with myopic degeneration. In fact, in Watski's original cohort, the myopia ranged from minus 3 and a quarter to minus 10. So they were all quite myopic. And then, of course, another thought has been that it's just an inflammatory or an infectious thrombosis. So similar to histoplasmosis. It's the same process. We just don't know what the bug is that's causing it yet, and we'll figure that out and then be able to link it. Those who... So the linked Epstein-Barr virus has been proposed as well. Tiedman, back in 1987, he did a study and showed that 10 patients with multifocal coriorentitis had high IgM-Titre-Srepstein-Barr virus, and so that... You'll still hear that today in the literature quite a bit. But a couple studies since that point, and one on my side here would by Spade, since that point it had not found that same finding. So it's been rather debunked a couple times since then, and so not considered quite as much. This was a study that was done recently in the United Kingdom I thought was interesting. So they're trying to show the link between PIC and MCP. And so what they did is they took 61 patients who had MCP or PIC, and they compared them to 92 population controls in the UK. And they were looking at 12 polymorphisms between the TNF-alpha and the IL-10, which is a region which is associated with a lot of UV-itis. They've recently been shown to be associated to have a high correlation with UV-itis. So what they show, they show two conclusions that contradict themselves a little bit. The first was they said that there's clear differences in the clinical course between patients with MCP and PIC, and in the prognostic significance. So they said the MCP patients usually have this more non-remitting course that continues on, and they require higher levels of immunosuppression to try to keep the disease down. So in that case, they said they're quite different. But then at the same time, they said that the patients had identical IL-10 and TNF haplotypes between the MCP and the PIC patients when compared to the general population. So, again, supports the thought that these diseases are very closely linked, and maybe that PIC just happens to be a less aggressive form of the same disease, and that's why we get less vitritus. Yes, to each other, between MCP and PIC. Yes. That's a good question. And they were vague on this one. I tried to look at it and see are they saying that's a statistical significant difference between the two of them, and they didn't say that. The way they worded it was they said, well, they're identical, and so I don't have a better answer for you on that. It is relatively small. The problem is, you know, it's hard to get 61 patients anywhere with you. That's by far the biggest one I could find of any of them. But, yeah. A recent study that was put out just in the last year also tried to identify typical lesions on OCT. So, they looked, this was out of Wilmer. They took seven patients, six females one male, and they looked at 27 PIC lesions located in those patients, and they tried to classify OCT changes you would see between active and non-active lesions. So, they characterized them as active if the patient had either a visual disturbance, if the lesions of the border were changing, or they could see a DEMA surrounding the lesion, or if there was hyperfluorescence on fluorescent angiograms. So, they had pretty strict criteria for what was active. And so, using that criteria, they said 24 out of the 27 lesions all showed involvement of the RPE. And one of the interesting things that they found from it was they could only show one lesion that had involvement of the coriocapolaris on OCT. Even though we hypothesize that that's the coroid and the coriocapolaris are what's involved with this. And so, just an interesting tidbit. So, the ones that they deemed clinically stable about using this criteria then, they found two main patterns noted on OCT. One was they'd have this RPE elevation with sub-RPE hyperreflective signals, and I'll show you some pictures of this. And then on another one, they had no RPE elevation, but they had disruption of the outer retinal layers. And one other interesting tidbit was of those that they called clinically stable. Seven of those lesions demonstrated alteration so they could show that the lesions were actually getting bigger and smaller during this time, even though they couldn't show that the lesions were active by forcing angiogram or by patient noticing changes. And then of those that were clinically active, the main other finding they had was that the photoreceptor cells, this ISOS junction, would not be visible during active disease. And then as things settled down, that junction usually came back into view where you could see it again. And I'll show you some examples. So, here's some clinically inactive. And this is baseline here. And these are the months. So, here's three months and four months on patient, right? This legion number six. So, here's our arrow where we're going through. And you see it, baseline, flat area, looks pretty routine. And this is, again, an inactive patient. At three months, you come in and you have this hyperreflective sub-RPE material. And you can see Brooks' membrane here runs contiguous, it stayed intact. The patient comes back a month later. That's flattened back out. And here's your ISOS junction. You have it run here and here, but you lose it during this phase of this material deposit. Comes back a month later. ISOS junction looks good and things have settled down. And this isn't a patient who really had no symptoms. Again, just a similar pick. Another patient here, legion seven, but you get the same picture. Again, this hyperreflective sub-RPE material flattens out. ISOS junction looks much better when it flattens out. Patient never had any idea that anything was going on. And then here's some that were clinically active. And really, the appearance is very similar. So, it leads to a question of what's active and what's not, I think. Here's a patient, Legion 14 at baseline. Pretty smooth running RPE here. Come back one month later. They now have some hyperreflective material deposited beneath RPE. 20 months later, it's gone. And then this one, this patient right here, Legion 27, a similar appearance, but it also correlates with these photos right here. It's the same patient. So, you see a color photo of the spot we're talking about. And then an early fluorescent angiogram and a late fluorescent angiogram. And they argue it's active because we get a little bit of late leakage around it on the late fluorescent angiogram. But obviously, not much leakage and not much activity going on there. One other interesting case. This was a patient who had originally presented and had anti-vegeth treatment given. Responded initially and then had a recurrence. So, she has this coronial vascular membrane you can see right here. And with further anti-vegeth, didn't have any response. So, they went in and surgically removed the coronial vascular membrane. Here she is a month out from surgery. And here she is a year later. You can see they bought a new OCT machine in the meantime. But she looks great. I think they wanted to show off the surgery a little bit at the same time, toot their own horn. But the main finding that came from it was helpful because it gave us our first look, our first chance to use light and electron microscopy to look at one of the coronial vascular membranes associated with Pitt. And I know Dr. Mamelis is probably the one in here who looks at this and thinks it makes sense. No, you don't. Well, good. Because that's what it looks like to me. But I'll explain to you what they were explaining in the chart. But they're showing this is the pigment epithelial layer here. And this is your Brooks membrane. And so beneath it, this is the main picture they were interested in. But beneath it, in the coroid level, they're showing these lymphocytes. And so they're saying this supports the hypothesis that this is an inflammatory process involving the coroid. Even though on the OCT, we're not seeing much coroidal change. So management of Pitt. I think Pitt really has a lot of interesting management questions. And so first of all, most patients don't require treatment unless they have involvement in the other eye with vision loss or unless they have a crotonial vascular membrane that develops. Most of them do well unless that happens. But obviously about half of them have that happen. So treatment options, there's a lot. Since this is more of an inflammatory disease, one of the best treatment options is systemic steroids. So these are a couple of different case series, small case series and a case report. There are not big numbers to look at on this. This first one was from Brown out of Iowa. They went back and looked at some of their patients. And so they said, well, we've treated four patients with Pitt with either oral or subtenon steroids. And three of the four didn't have any improvement of their crotonial vascular membrane. So the very first study is to come out talking about treating it with steroids. Two years later, then, out of the United Kingdom came this study and it really changed the way we treat it because they said, well, we took 12 eyes that had these subfoldial cronial vascular membranes from Pitt and we put them on oral prednisone at a big dose, you know, 60 to 80 milligrams and they started a wean after that. And they said 10 of the 12 eyes had improved or stabilized vision after that. And nine of them had resolution of leakage on fluorescent angiogram and three of them had improvement. So all of them had some improvement. Nine of them had completely stopped. And then of those four patients ended up needing more steroids. So that really changed the way Pitt was treated at that point. And then Levy, just another one in 2005, showed another patient who had vision of 660, which improved to 6.9 with treatment of oral steroids. And he noticed that the lesions in the posterior pole became much smaller and the leakage stopped on forcing the angiogram. Another treatment option then is intravitral steroids, trying to get it just that medicine right to the area of the inflammation. Holocant, this is the only study I could find, but he's the only one I could find who's used a reticert device for Pitt. So he put it in saying, well, this is a long disease and we'll put it in and for 36 months they'll have coverage. So he put one in on a patient and they ended up having a relapse of the cronial vascular membrane for 18 months in and had PDT, which was successful, but it didn't stop a recurrent neovascular membrane from developing. And then Sam did a study where he talked about using intravitral trimestinal loan on a couple different patients who were pregnant and had good results, one stabilized, one division approved substantially. PDT and steroids probably up until a few years ago were probably recognized as the main treatment option. PIC lesions, PIC neovascular membranes seem to be quite responsive to PDT. This was a study that was published and written in 2008, probably right at the time when VEGF started to really overtake PDT for the treatment of this, but they had 14 eyes, followed over a 12 month period who were given both triumphs, intravitral trimestinal loan and PDT and they had a substantial improvement in the best corrected visual acuity from Logmar from 0.5 to 0.2 a year, one year follow up. Many studies supporting that. And then anti-VEGF in the last few years has been kind of the main treatment we've seen. This was the largest cohort I could find. It came out of China, but they had a lot of people in China, so probably more PIC, but they took 12 patients, which I thought was interesting as a side note just because they say 97% of the treatment is Caucasians, but in China he had a cohort of 12 diagnosed with PIC, so he either gave them he gave them a Bevacizumab and they came back if they had any recurrent activity or leakage and they were all followed for 12 months and he had an improvement in baseline corrected vision from 2062 to 2034 and all eyes he said it stabilized or improved. Nine eyes it showed grid and two lines of improvement and vision. And one other interesting thing was that they had to take a trisil phase after 12 months. It varied per patient so when they came back if they were considered to have continued activity they received more. So every patient was different but 12 months followed, they were followed monthly and if they had fluid on OCT or they had leakage on FA they were given another injection. Yes. But again they only have 12 months of follow up and then immuno modulation. Turgoglue in Wilmer has recently started treating most of his PIC patients with cell set. And so I thought this was an interesting study but he had, he showed 8 patients who he had followed who had at least 2 recurrent episodes in the previous 12 months and had 12 months of follow up prior to being started on cell set and 12 months of follow up after. And so of these patients they experienced 19 attacks of recurrent disease. I think the main point on this slide during mycophenylate mycophenylate the main point though was the attack frequency. So before being treated they had about 1.09 attacks per year per patient and after treatment decreased about 4 times to 0.23 and that's what the year of follow up on cell set. He's a big proponent of treating him with a lot of modulation to try to slow this down. So here's our patient back to her. She returns 3 months later her headaches continue to worsen and now she has these constant flashing lights in the left eye. She did have gallbladder surgery 2 weeks prior and felt like that. Just sped everything up. She also complains of more metamorphopsia and more darkening in the left eye. A vision has decreased now in that left eye to 2050 and the remainder of the exam is normal. Here's our color photo. You can see quite a bit more hypopigmented lesions over there in that left eye compared to previous. And here's our funnesotofluorescence I'll point out. So here's her when she came in the first visit and here's 3 months later you'll notice just a dramatic increase in the hypoautofluorescence spots and also in the hyperautofluorescence surrounding that. Definite advancement. The right eye really looks pretty darn stable. Again forcing angiogram in the right eye now you have additional lesions here. Questionable if there might have been a little bit of leakage here but we didn't think we didn't think so at that point. ICG in the right eye has unchanged a couple hypoautofluorescence spots and in the left eye much more dramatic change. OCT again looks great in the right eye. Now in the left eye you see these sub-RPE hyper florescence spots hyper-reflective deposits I should say. Visual field at that point shows this enlargement of the blind spot and temporal loss in the left eye. So at that point she gets a more thorough work up. She has a lumbar puncture done. It's normal. She started on oral prednisone after doing these other studies. Her partner for Angola was negative. Bartonella was negative. She had Epstein-Barr virus titers drawn. The IgG was high which is interesting quite high but the IgM not much to make of there. The rest of the work up was negative. So she started on oral prednisone 60 milligrams. She comes back six weeks later. She's feeling a little better. Vision's a little better in that left eye. She saw that gray spot in the center of her vision but it's better. She thinks and some photophobia. Vision's improved. So last time she was 2050 in that left eye. Now she's back down to reading the 2020 line and she has this definite central scatoma on fields in the left eye. So here you can see prior visit and now today six weeks later you can see that those hypopigmented spots have kind of settled down. Things look a little more stable in that left eye. And on the fundosodal fluorescence you probably see the most impressive documentation of that. You can see just how that hyper and hypoidal fluorescence has improved dramatically there with the oral steroids in the left eye. The right eye remain the same. At this point though when we look at her fluorescing angiogram in the left eye she, here's early and here she has this continued hyper fluorescence that seems to expand a little bit centrally there. ICG really is impressive in the left eye how much better it looks. So here it is today and here it was the visit before. So quite an improvement on those hypo fluorescence spots. OCT stable in the right eye again and much improved in the left eye. So we continue her at the prednisone wean she's now down to 40 and at that point she gets an avasin in the left eye because we were concerned about that hyper fluorescence in the left eye there on the fluorescing angiogram. I think one other thing I wanted to show was just on the ICG you see it again a concern there maybe there's some hyper fluorescence which would be consistent with a muscular membrane. So she comes back another six weeks later. Vision continues to improve mainly she's just getting some symptoms now from the steroids. So she has ulcer and anxiety she has new colsores but she's doing great so we're not ready to stop and we're going we're going to push ahead. Vision wise she's 2020 we're all thrilled and I'll just tell you this looks the same as before there's no change. Fluorescence you do see some more spots here though now you know you look at it and you could say well we're seeing some early changes. Fluorescing angiogram there's no more leakage we were concerned about this little area right here that we thought was leaking before that's definitely not leaking on here. OCT continues to look better. So we continue the wean we start her on valcyte for the colsores and plug ahead. Six weeks again she's still doing well she's down to ten on the prednisone things look pretty much the same so we're going to keep following her. Comes back six weeks later vision's down a little bit she says I feel fine but we can only get her to 2040 and now she's pregnant and this is what Dr. Vitaly's head did when he heard that that's when you got to be kidding me. So the game changes a little bit. Really on the funnest auto fluorescence again you know even though she's down a little bit we settle changes but they're not much different you know and so you start debating how aggressive do we be. She's off all steroids we say let's watch come back in six more weeks we'll take another look. She comes back six weeks now she feels she's much worse vision color changes are bad she's a college student she says I can't do my work because I can't see to read her it's all the time and I'm 11 weeks pregnant. Vision wise she's down in both eyes now she's 2040 minus in the right 2060 minus in the left and now she's got a bilateral central scatoma she's describing on AMSLA and here's her funnest auto fluorescence so in the right eye you can see that these hypopigmented areas which correspond to RP drop out are much darker and you see this hyper auto fluorescent area here which we haven't been seeing before in the right eye this is sick RPE and then in the left eye you can really see the sick RPE centrally right here in the fovea some expansion of these spots she's doing worse. OCT here's her right eye this is the first time we're starting to see changes in this I think it's a great photo that describes some of these outer retinal layer changes that you see described with active disease in the one paper I cited and then the left eye again you have these sub-RPE hyper reflective deposits bigger now than they've been ever so we have a long talk with her because she's pregnant and so it really changes some of our options and what we recommend is intravitual Tri-Amcinolone Tri-Essence we tell her we think this is very safe with your pregnancy we put the medicine right where we want it she comes back four weeks after that and really feels like she's doing a lot better she's 15 weeks pregnant at this point vision has gone from 2040 back to 2020 in the right eye and vision has gone from 2060 minus to 2040 plus in the left eye so we're pleased with that funnesotl fluorescence you see some improvement these lesions here are smaller again and this here does look better it's quieting down here's her OCT really you just have that spot that was there before and she has just kind of a loss of her ISOS junction right there and these are settling down here in the left eye they're smaller than they were so we say well let's you've got the Tri-Essence in let's see you back in four weeks the frustrating thing when she comes in and she's very careful at this point she says I saw you guys you gave me the Tri-Essence you told me it was pretty safe I went to my OBGYN a couple days later and he tells me it's class D and there's a very good chance so just an interesting side note Tri-Essence on a C at night is pregnancy category C Tri-Essence is just the exact same thing minus the preservative yet in everything I can find it's listed as pregnancy category D which I'm sure is what her OBGYN looked up and told her all of this with she don't want that in I briefly just put the drug categories I won't go through them for you but in study C animals have revealed adverse effects in study D they say there's positive evidence of human fetal risk and so the risk with steroids we all know is cleft palate in fetuses but so we pull up this study we had a conversation with our OBGYN about it to try to prevent further problems but this is the only study really that goes into this it was done in 2004 but what they did was they took 20 consecutive patients and after giving them 20 to 25 milligrams we don't really do that anymore they drew their blood and they checked the serum levels of Tri-Essence the problem was it wasn't done perfectly so they drew it at 13 plus or minus 19 days after this was not the best design study it ranged from 4 to 92 days but in 18 of those eyes 90% they couldn't find any Tri-Essence alone in the serum in 10% 2 of the 20 patients they found these were samples taken in 5 and 7 days they found 0.5 micrograms and 0.8 micrograms which is nothing when you consider that our average daily production of cortisol is about 15 to 20 milligrams even though this is 4 to 5 times stronger than that it adds up to nothing from what we make and so we tried to reassure her she's not really hearing it very well she's saying well I won't do another injection I'll go blind before I let you know and so anyway just a point on that it should be quite safe I just wanted to make that point and we made that with her and sent a nice letter to OBGYN informing him of that but that bridge was burnt at that point and then another thought on anti-vegeta I wanted to briefly touch on this in pregnancy so this came out of Terontola is one of the retinocris in Iowa came out with this but in 2010 so they they took 4 patients those 4 patients had a total of 5 pregnancies and these 4 patients they treated with a total of 13 injections of Avastin during their pregnancy 2 were treated during the first trimester 1 woman in fact had 3 injections given during the first trimester and then 2 were treated 2nd trimester 1 was just 3rd and then they also had a patient who got 5 injections while breastfeeding and so they said well we did this and 5 patients we had no adverse events as we all know that's a very small number yeah it's they published it but no one feels comfortable now giving Avastin after having seen this one other thought I thought it was interesting they used Avastin so I did quite a bit of reading on this but most small drugs cross the placenta by simple diffusion so bigger drugs have to be carried across by active transport so the classic example they always use insulin which is 5.8 kilodaltons it has to be actively transported across the placenta to the fetus so Avastin is 149 kilodaltons much bigger even Lucentis is 48 kilodaltons and then the other way that fetus is obtain these antibodies is by an FC receptor that binds the FC portion of the IgG so it makes a lot of sense that Lucentis would be much safer because they've removed that FC portion from the molecule whereas Avastin still has that FC portion of course there's no study that's been done on this to show the levels that cross the fetus but just theorizing on it would make sense that Lucentis would be much less likely to cross it is a little bit smaller but it's still much bigger than insulin and it doesn't have that FC portion to help carry it across and then one other study I wanted to cite here was just this came out of Italy I thought it was really interesting so they unknowingly gave Avastin injection to two women who were pregnant both women one was four weeks pregnant one was five weeks pregnant at the time of injection and we're not aware of it both women then had spontaneous abortions one week after the injection of Avastin and so again it's all anecdotal but this is just the other study we have that's been reported on this no it doesn't tell us much because then you have this question this was the other one I cited Wilcox in the New England Journal of Medicine in the 88's that you know the incidence of spontaneous early abortions is 31% so it's hard to read much into any of this one last couple of last studies I wanted to mention just the levels that we see change with Avastin injections in the eye so this is one where they gave Avastin injections in the eye in patients with type 2 diabetes and then 30 non diabetic control patients and then they sampled the blood for serum VEGF levels at one day, seven days and 30 days after the injection so the average VEGF level before was 114 at day one it was 9.7 after the injection 11.7, 25.9 so they had a substantial decrease in serum VEGF levels correct I'm sorry it was part of the 114 I don't know I don't know what it was after I don't remember I'm sorry but this other study kind of did the same thing I think it was a little bit better done and it was just published this month but they took 30 diabetics, 30amd patients and they randomized them to 10 Lucentus, 10 Avastin, 10 Machigin which I thought that was a dinosaur but they did and then so here are the diabetes patients at baseline 72 this is the serum VEGF levels again 72.2 day 7 is 13.7 day 37 dramatic, highly significant difference in the serum VEGF levels after injection whereas in the Lucentus and in the Machigin levels the changes was not significant they couldn't show a difference so I thought that was the better done study again showing a dramatic decrease in serum VEGF levels associated with Avastin one other question that came up in her you know if it's safe to use fluorescein angiography during pregnancy it's kind of a trick question because no one knows it's like everything in medicine no one tests it so the only study we have exactly so the only information we really have came from this study in 1990 they sent out 399 retinas specialists a questionnaire saying have you used fluorescein angiogram 309 said no, 77% 90 said yes they had so then they wanted to know what results did you see of that so of the 90 or the 23% who had used it they got detailed information on 116 patients the main side effects were nausea, vomiting like you would expect with fluorescein angiogram birth anomalies they had of those 116 they had one on the scented testicle one syndactylin and then they went and further broke it down to 41 of the 116 had the FA perform in the first trimester so of those 41 they had four deaths 10% two were thought to be due to severe eclampsia one was months later they didn't think it was related to that at all but it's hard to know and then one occurred three days later and a healthy woman who was four weeks pregnant so the authors of this studies they also pointed out eight children were born to mothers with eclampsia had birth weight, low birth weights of 116 and then with that information they said well we conclude that fluorescein angiogram is one of the main implications so that's really been challenged in that study their conclusion they made is what got them in trouble people have had a big problem with them saying that from that one study anyway so she comes back now four weeks later again and she's doing much better she's 2015, she's 2025 plus in the left eye small central scatoma in the left eye but doing better than she had been fluorescence is pretty stable she continues to look a little better OCT in the right eye again you have this little ISOS loss but that does look better than it was before and these are continuing to settle down that's all this is why you don't let your kids watch nacho libre in case you wanted to know but questions at all nothing that I saw the only things I saw that were interesting with her was most authors speculated that pregnancy would kind of be immunosuppressive and decrease the flare up of there were two case reports I saw individual case reports of patients who had flare ups during pregnancy much like our patient but nothing regarding eosinophils there's definitely involvement there we're just not seeing it