 Good morning. I think we'll get started. I'm Leah Owen, one of the first-year residents and just would like to introduce Trent this morning but first just quickly. I've been away and this is why and we're just so thrilled to welcome him to our family and I appreciate all the support the department's given me the time to have him and figure out how to take care of him. So Trent has been a wonderful intern this year and it's been a pleasure to work with him and I'm so glad he's in the program and excited to have him full time next year. He has a little bit a few more weeks with us before he has to transition to internal medicine, unfortunately, and this morning he's going to discuss with us a subacute vision loss bilaterally in a middle-aged woman. There we go. So I am the intern, but I'm pretty nervous right now, I'm actually, so this is my first grand rounds here, I'm a little nervous, the nerves might get the best of me and I might fumble, keyboard, fumble over and over. You see the pattern there? Hopefully we come out victorious at the end now. Snow was there, right? You got a couple of them, right? So that's what, the third quarter? So anyways, our case today is about an interesting case we had come in to the continuity clinic over the last month. It's a 44-year-old female who's a prisoner here in the state of Utah who had loss of vision, left greater than right over the last couple of months. A few months ago she noticed the vision was deteriorating so she saw the prison eye doctor who checked her vision and told her that she had 20-20 vision but that she did have the beginnings of some cataracts. So as the vision continued to get worse she thought it was due to the cataracts, but then it got to the point where she was only left with a little bit of an area in her left eye in the lower part of her vision where she could see shapes and colors and then the right eye started to get bad as well. At this point she was a little bit more concerned and decided to go get her eyes checked again. And the prison optometrist told her that she had bilat or saw that she had bilateral disc edema and sent her up here to the Moran Eye Center to get evaluated. Yeah, so that's that's what we got but it could not it might not have been accurate. So the past medical inocular history we have for her, she's a high mile in both eyes, amblyopia in the left eye. She has high blood pressure, the highest being 200 over 105 while she's in the prison. She has valvular disease and we believe is mitral valve just don't know exactly what she she can tell us exactly what it was. She has depression, anxiety, she's had some TIAs in the past. She has hepatitis C with subsequent UV bruising. She has asthma, heptic ulcer disease and GERD, and then a history of head trauma with subsequent seizures the last being in 2003 and then she's had multiple abdominal surgeries, most of them stemming from trauma and abuse. Her medications were Venma vaccine. She was on a beta blocker until she went to prison and then that was changed due to cost. So she's on quantity and lysine up real for blood pressure control and then she started estradiol a couple weeks ago and then she takes ibuprofen as needed. There's no family history or any ocular history and then there's a family of three for diabetes and high blood pressure. She was incarcerated about 10 months ago. Before that she worked at as a custodian here at the U and she does not drink any alcohol. She smokes and she has a history of meth, heroin and cocaine abuse. Review symptoms or symptoms were positive for a headache and then the pulsing sensation in her eyes but she denied any eye pain, any dimouts, any pulse synchronous tinnitus, floaters, flashing lights for recent trauma and she was not obese. So at this point in time from this kind of hammy explanation of what was going on, we were kind of trying to put together differential diagnosis with kind of the information that we had so we before we started the exam kind of know what to look for. Tom, what would be on your differential at this point? It goes both ways, man. She was not diabetic. She was not on interferon that we know about but who knows as she knows. Yeah, so that's a good start. So we were thinking originally kind of some neurological issues, possibly some vascular causes of the trauma she is in prison or maybe it was like a pseudo papillote, you know, somopic disperusion or congenital anomalous disc, something like that. So that's our initial working diagnosis as we went in. Her exam she was 24E in the right eye and then 2800 in the left. The pressure was worth it normal and essentially she had the central scopoma in the left eye. Her eyes had been previously dilated so it was hard to check for pupils but they did slightly react the right better than the left. The extra octenum muscles were full and then the rest of the anterior exam, the solid left exam. Then we got to the fundoscopic exam. We'll zoom in on the right eye here. I'm going to go even more uphill and see if my chief can help me out with this. Bryce, can you kind of help describe this photo? Okay, good. Yeah, so like Jeff pointed out, we didn't exactly talk to the eye doctor at the prison. It was kind of handed down. So we don't know if they really did see disc edema or if it was hemorrhages or whatnot but there definitely is not any, I mean the disc margins are clear. It does not look to be any disc edema there and then like Bryce pointed out, we have a lot of other pathology going on in the retina. And then here's just another view and you can kind of see these streaks that he was talking about that kind of radiate from the optic disc there. And then we'll go to the left eye and then I'll go with the other chief that I worked with for a while that always had me do a lot of stuff for him. Grant? You want to go ahead and help me out here, man? Exactly. Okay, go to the other photo there. Yeah, we'll go to another picture of the periphery there. Kind of these spots out there like that. So those are our fundoscopic pictures. We got the OCT and this is the left eye obviously and here we see a lot of intra retinal kind of cystic edema and kind of some subfibrotic scarring or fibrosis there as well which was consistent with that area that Grant was describing of that, that area of fibrosis. And then in the right eye we have some subretinal fluid and then another cut goes through one of those kind of whitish lesions that Bryce was talking about and it goes right there and it shows that it's an intra retinal. I wish I had the pointer. Oh, it does work. So right there that goes right through that that kind of drusen-like lesion that we were seeing and but it shows that it's intra retinal probably like an intra retinal exudate or something that's going on. And we got the red free images that just kind of once again points out this area of almost fibrosis and then we kind of got these streak lesions coming out from here these areas of coreo-retinal atrophy and RPE, hypertrophy and then maybe some heme over here. So on the FA, the left eye, once again we kind of have this hypo fluorescence here in that area of the fibrosis that we were seeing earlier and then as you see later these kind of window defects pop up where the area of the coreo-retinal atrophy that we saw but we don't really see any leakage per se and then a little bit later around 32 seconds you see these streaks kind of are starting to become hyper fluorescent and then these window defects are becoming even more prominent. And then late in the FA and the left eye you see this this area just continued to brighten the margins stayed the same it never expanded it just continued to get brighter and brighter you know probably just due to staining of that of that old scar that she has there and then there's that cut through that area just showing again that area of sub-retinal fibrosis and then here's the red free the right eye you can see these little specks pretty prominently here in that area of the sub-retinal probably a sub-retinal hemorrhage and then the streaks coming out the FA of the right eye was kind of the same you had a little bit of hypo fluorescence there with the hemorrhage and then it started to become hyper fluorescent here and the same thing the border stayed the same but it just continued to get brighter and brighter and there's no real we didn't really see any signs of leakage in the vasculature and then here it is late staying the same it's bright but the borders are the exact same and then here in the OCT it cuts through that area and right about here corresponds to there and we can see a little bit of sub-retinal fibrosis as well so at this time we're thinking we might know what's going on and the attending I'm working with is very smooth and so he just kind of brushes back to her hair and checks out the back of her neck and that kind of clinched it for us so here we kind of got a little a little rash it looks kind of like a plucked chicken and she says she's had that since she was little for almost as long she can remember maybe like that but she's kind of always had that rash there so this time we think we kind of know what's going on anybody have any ideas of what she might have yeah so we're thinking of pseudosanthylmalasticin so the epidemiology of pseudosanthylmalasticin it's an estimated prevalence of one in 25,000 one in 100,000 area of the world that has the highest prevalence is actually South Africa anything is due to a Hardy-Weinberg effect women are affected twice as often as men and then the life expectancy is normal in most patients it was originally thought to be an autosomal dominant or or just a denoval mutation but recently they they feel like it is autosomal recessive as they have not found a pedigree yet with three generations that have been affected by the disease it's a mutation the abc6 gene on chromosome 16p13.1 and the abc6 is part of the subclass C of ATP binding cassette transporter which transports from the intracellular into the extracellular space or into cell compartments and then this encodes for a multi drug resistance associated protein or the MPR6 which is expressed highly in liver and kidney but not so much in tissue affected by pseudosanthylmalasticin namely the skin cardiovascular system in the eye so it may be regarded as a systemic metabolic disease with altered levels of yet unknown molecules due to a defective MRP6 transporter and the thought with this is that it may disrupt or it may cause low levels of certain factors that are needed to to inhibit the the aberrant mineralization of elastic tissue or elastin under normal calcium and phosphate homeostatic conditions the the rate of synthesis as well as degradation of elastin has been found to be increased in skin specimens of PXC patients and then it primarily affects the skin cardiovascular system in the eye and then the abc6 functions in regulation of extracellular matrix movement between the inner retina and RPE Brick's membrane complex which could possibly be the the cause of the androids to the defects we see there so the skin manifestations of the disease this is the primary organ system that's affected we usually see the rash it'll usually appear around age of 13 is the average and then the average age of diagnosis for the disease is 22 so there's a little gap there nine years from the time of first symptom or or sign of the disease to to the age of onset or the age of diagnosis and the rash like we saw earlier it's kind of described as this plucked chicken appearance um other people may say it looks like um like an orange peel uh texture there but they're they're usually asymptomatic soft particles of yellow ivory color and then they present this reticular pattern and then the similar skin manifestation may occur in other diseases so it is not happening to monitor pseudosanthoma elastocone it can be seen in cutaneous elastosis beta thalassemia pageant disease and other diseases as well the interesting thing though is that pxc can be diagnosed by or confirmed by a skin biopsy and then the uh the skin biopsy shows kind of these fragmented clustered calcified elastic tissues in the middle and lower dermis and then the skin manifestations do not play a role in the in the course of the disease that the course of the disease is determined by the ocular and cardiovascular manifestations so the cardiovascular manifestations navangina in the reduced pulse amplitude artiller hypertension restrictor cardiomyopathy and our patient she had this valvular disease we think it was mitral valve we don't we don't know for sure what it was so we sent her to get an echo to get a cardiovascular workup and then also she uh and then there's this early onset atherosclerosis she has some tias um in the past as well and she did also have hypertension um the most common thing is the early onset atherosclerosis and that's probably the most the most commonly debilitating aspect of the cardiovascular part of the disease and then 25 we'll develop renal hypertension and then the other thing to to keep in mind for these patients is that it is a systemic disease so we might diagnose it as uh you know eye doctors but there are other there are there are other things that may be more pressing we should probably warn them about you know all these things that could happen and also the gi hemorrhage that is pretty common so if they have any sign of gi hemorrhage they have melanin or chemists or anything like that that they should um you know be aware of that that could occur you know with the ocular manifestations of the disease this is actually the photo from our patient this paude orange look I can't pronounce it all but yeah yeah so I I do Spanish not French so um but these are the first visible changes in the retina it's most prominent temporal to the phobia it's usually at the level of the rpe and it typically typically precedes the angiois streaks by one to eight years and it'll usually be bilateral in her her left eye was a little bit more prominent in the right but it was bilateral and then we have the angioid streaks which are the breaks of the calcified and thickened bruke's memory uh caused by a mechanical it's thought to be caused by the mechanical stress of the extrinsic and intrinsic ocular muscles the angioid streaks will originate from the optic disc going out just like you see here and they might convert concentrically around like that um they differ initially with our patients since she was so severely myopic we were wondering if those streaks we saw were my or uh lacquer cracks but lacquer cracks are usually they don't usually radiate like that they're usually kind of sporadic and they'll crisscross at the posterior pole and don't really have this pattern of radiating out from the disc um they'll also possibly an old corrodal rupture for the corrodal ruptures user and the concentric of the disc like that and then only a few cases of angiois streaks have been identified under the age of 12 they've never seen them at birth it's usually bilateral and then the big thing is that it may uh may progress to a defect in bruke's membrane with the atrophy of the coriocapillaries the RPE and the photoreceptors which can then lead to an ingrowth of fibrolept vascular tissue through the defect giving way to secondary coradal neovascularization and sub subsequent disc form scar and sub-retinal fibrosis and atrophy and this is probably what we were seeing in the left eye of the patient with all that that area in the mac of the all that sub-retinal fibrosis and atrophy so the differential of of angioid streaks we're all taught this pepsi mnemonic but i like to you know pepsi that doesn't really include everything so i was thinking maybe a better mnemonic like pepsi ampsifstaff should it do that and that's pretty pretty easy to remember right now well there's just a lot of there are a lot of things so this pepsi i mean the p the pseudosanthoma is definitely the most common but we can't forget that it could be so many different things and like tom was saying does she have diabetes so diabetes could even cause it or you know hypertensive coronary disease so just when we see the angioid streaks probably branch out a little bit more than the pepsi but the pepsi definitely will cover more another ocular manifestation of the disease is optic disc drusen she did not have any optic disc drusen but this this can occur it actually occurs about 21 percent of time when you have angioid streaks due to pseudosanthoma but about 25 percent of the time when you have angioid streaks due to another etiology so it is not specific at all for this disease then the last thing that i want to talk about are these comitio lesions they're these small choral retinal atrophies they're usually seen in the mid periphery and they may have this halo of pigment hypertrophy and then if you can kind of see this almost comet tail pointing toward back towards the disc the oct will show small intratenal cysts with a defect of rpe underneath and these lesions are actually pathodontic for pseudosanthoma so i think our patient kind of had some of these little lesions here now a diagnostic approach the best thing i mean obviously a dilated fundus exam the reason to get a fluorescent angiography is if we suspect a cnb and see if there's any leakage it's not very helpful in diagnosing or to see like to be able to visualize the angioid streaks just because they can it can appear hyper fluorescent hypo fluorescent and it can you know it's not always they don't always appear the same but it's the most helpful if we suspect a cnb you can also use an i ga which may be superior to f a for visualizing the angioid streaks and a large retrospective study kind of went through all the all the cases they had and and determined that the the streaks and the poldoange they appear similar almost almost all the time they'll either be hyper fluorescent together or hypo fluorescent or combined but they're they're either one or the other but they're going to be the same within the eye but they can but that's the other thing to keep in mind they can be hyper fluorescent or hypo fluorescent or full for track light they're not they don't always appear the same so this is just kind of a picture they have the the poldoange out here and then the angioid streaks and then you can see the i ga about 30 minutes later they're a little hyper fluorescence and then another thing is you can use auto fundus auto fluorescence the angioid streaks may show areas of increase as well decreased faf again and then the corioretinal atrophies will show an increased faf the nice thing about this tool is that you can use it to monitor the progression of rpe changes or the cmvs or alterations for x memory the treatment for pxc there is no treatment that is directed direct or that's that will target the pxc per se but we can kind of treat the corridor neovascularization that develops that's the only time that there is treatment for this the laser photocoagulation will halt the progression of cnv but there's a lot there's a high rate of recurrence visual loss and central scotomas the other thing they try is macular translocations or sub-ovial cnv excisions but those are not successful intervitory of trancelone has a no clinical effect and then photodynamic therapy and all the trials i looked through there's been mixed results some patients improved a lot of patients actually continue to lose visual acuity but the treatment of choice at this time would be anti-veget therapy and the largest there there are a lot of publications a lot of different studies where they they've used anti-veget therapy but they're all pretty small that i found they're mostly single digit eyes this was one of the larger ones and one of the more recent studies that was published and in their study they had 16 eyes the mean age was 55 they received about six six and a half injections plus or minus 5.7 over 28 months in order to follow it over that period of time and it was shown their VA improved from 2080 to 2040 and then the central retinal thickness decreased from 254 to 214 plus or minus so our patient at that the day that she was diagnosed was sent to retina and they injected her right eye with a vastin and then she was seen yesterday or two days ago and had a repeat OCT done so here's a repeat OCT and there still is some sub-rentinal flu but it has decreased a little bit as you can see the the sub or the central retinal thickness went from 392 to 314 so she was given another injection on monday and then she'll follow up in a month and her vision had not changed so the visual prognosis of the disease basically the visual outcomes are dismal there is no treatment to at pseudo xanthoma elastocone we can only treat the the CNVs that form and try to decrease the progression and then once that central disc to form scar forms there's really not much we can do the patient has 2800 vision in that left eye and there's really not anything I mean there's not much we can do at this point so the big thing is to start the treatment early as soon as you see any sub-retinal fluid or diagnosis did to try to keep the fluid at bay with anti-veget therapy and then total blindness resulting from angioid streaks due to pxE is very rare so the conclusions I drew from this case is that it's a systemic disease with ocular manifestations and my short time here in ophthalmology I tend to hone in on the eye and I haven't done my internal medicine months of intern year so yeah and thankfully but but you know the this patient the more pressing issue is actually to get a cardiovascular workout she has this history of TIA she has valvular disease she might go blind but the cardiovascular manifestations of the disease are killer and so it's important to always realize that a lot of these diseases that we see are systemic diseases you know we're just seeing ocular manifestations and then they need to be referred appropriately to the to other subspecialties in medicine and then it's just one of the many causes of angioid streaks well it is the most prominent or the most common cause of angioid streaks it is only one of many there is no good established therapy anti-veget is the treatment of choice when CMV has occurred and then another thing is to advise these patients to abstain from high risk activities or high risk sports and always wear eye protection these are my references and then the last thing I want to leave you with is something I learned from the astute Dr. Petty while working with him is that hard work perseverance and years and years of sending fan mail you might be able to receive a picture of this she might finally respawn now thanks any questions so yeah so there they they think it's at the level of the as far as the the genetic testing I think I just saw a paper recently where they are start they can start to test for it but I don't think they're they really do because the cost-to-benefit ratio just isn't really there you can diagnose it by other ways with a skin biopsy or other things like that but they just identified the gene a few years ago and so I think they're still working on that yeah I'll have to I mean I'll have to read again on it I'll let you know I'll look at it a little bit more but then if they think it's at the level of the so they think that it helps to in regulating that's your cellular matrix from the inner retina and the RPE Briggs membrane complex I think it's at the level of the RPE but I'll look again because I know it moves from that's right around the area where it is but I'll look again yeah yeah I'll look in I'll let you know no I was surprised by reading that as well I just read in the review I never saw that really mention yeah so I hey Sam