 So next up will be Ashley Bourges-Los. She's one of the fourth year medical students from here in Utah. She's going to be presenting on ocular manifestations of plaque when old toxicity. She's in the exciting phase of interviewing and that sort of thing. All right. Good morning. Thank you all for being here to listen to me for a second time in just a few short months. My topic today, like Russ said, is ocular manifestations of plaque when old toxicity. I'm going to just for a quick overview, I'm going to talk about case presentation. I'm going to talk about the history of plaque when old. The guidelines for screening for patients on plaque when old and then finish with our assessment and plan for my patient. So this is a 36-year-old woman who presented because she was worried about eye damage due to the plaque when old that she's been on for the past 18 months. Her dose is 200 milligrams and that equates to 6 milligrams per kilogram per day. And she complains of red and green dissaturation in the right eye compared to the left. She's also concerned about new onset of white showers, bilateral eye pain, and repeated visual zigzags, which block out her vision and always occur in the same sequence. This phenomenon has occurred every other month for the past six months and they are easily aborted with ibuprofen. She feels that bright sunlight and fluorescent light seems to trigger these episodes. And she notes that in the previous two or three years, she's had about one or two of these zigzag episodes and without a headache that usually lasts about 30 minutes. On review of system, she's positive for carcignus as a child and carcignus currently. She has no history of headaches ever previous to this. Her pathological history is positive for Lycan planus follicularis, for which why she is taking the plaque when ill. And this photograph demonstrates the severity of this disease and suggests why she's treating it aggressively. She has no other past surgical history, no ocular medical history, and she's never been hospitalized. On examination, her visual acuity was 20 out of 20 on both sides. Her pressures were 14 and 16. Her visual fields were full of confrontation. Her extra ocular movements were full. Her color testing was nine out of nine in both eyes and on slit lamp and fundoscopic exam, it was completely normal. Her cup to disc risk ratio was 0.2 on both sides. Her flicker test was 37 on the right and 36 on the left and her 10 to visual field was also completely normal. On her multifocal ERG, you can see a few areas of depression. So you see kind of a little area here and a little area here. But on talking to Dr. Krill, he was skeptical if this was real or just result of the tension she was experiencing because with muscle contractions in the neck can cause the similar areas of depression. So a little bit about plaque vinyl. It's an anti-malarial drug that's used to treat various autoimmune diseases, as you all know, but what you might not know is that quinine was the first anti-malarial that was used for this purpose and that started as early as 1894. A little over 50 years ago, chloroquine and then plaque vinyl hydroxychloricin fell into favor because of its more favorable side effects. And then it was the treatment brought in beyond lupus to include rheumatoid arthritis, connective tissue disorders, as well as dermatologic disorders. And today it's even used for off-label for a lot of other rheumatologic diseases. The first case report of retinotoxicity was published by Hobbs in 1959. And the patient had been using it for malaria treatment. Following that, about two years later, came in, started rolling in a ton of reports that of retinotoxicity in patients who had used anti-malayers for autoimmune diseases. So the toxic effects of this include decreased visual acuity, visual-filled defects and color vision defects. And here we kind of see a worst case scenario where you have the central scatoma with the foveal sparing. You have RPE depigmentation, right here. And then the classic bullseye maculopathy over here. This is what the screening guidelines are hoping to prevent. A lot of times when they get to this point, it's gonna be too late to do anything about and a lot of the damage can be irreversible. This is another worst-case scenario of a multifocal ERG. The areas of depression go beyond just this paracental region and go out into the periphery of the retina. So the question is how much and how long does it take for this to occur? And there hasn't been, even though people have known about this since 1959, there haven't been a lot of studies that have been shown a lot. But a recent study came out in 2010 that involves 4,000 patients who had been on long-term plaquinil that showed that the things that cause the most damage are if a patient has had a cumulative dose of over 1,000 grams, if their daily dosage is over 6.5 milligrams per kilogram per day, and if they've been on the drug for more than five years. And it also showed that the prevalence increases of plaquinil toxicity from about two to three cases out of 1,000 to one out of 100 cases after five years. So as far as intervention, there is not a lot of treatments that are available to reverse. There's no treatments available to reverse damage. However, reversal is often possible if the drug is stopped at a very early stage of functional loss. However, there has been reports of continued depigmentation with functional loss because the drug often stays in the blood after discontinuation. And because I named this ocular manifestations, I wanted to give a quick shout out to the corneal and glaucoma guys and gals. And plaquinil can also be associated with lens of pacification, world care topathy, which looks very similar to amiodarone toxicity or Fabry's disease. And you can also cause ciliary body dysfunction. So I like it when lectures kind of break it up with a few pictures. And so here's just a few more photos from my trip that I took last year. So bear with me, I know I've already shown you a few. So this is Mollay National Park up in Northern Ghana, some mom and baby war hogs. This is on a trip I got to go with my father and my mother and my sister and brother-in-law of the Serengeti. It's one of my favorite photos. And this is a Masai woman who was just in a village outside of the Serengeti. All right, so I wanted to have you take that break so you guys pay attention for the current guidelines and recommendations. So this came out in May of 2007, sorry, 2011. And it came out because of that study that I just told you about that came out in 2010 that had the 4,000 patients. Because previous to any of these recommendations, the only reference was the physician's desk reference, which said that they should get examinations quarterly. And then in 2002, they came out with these same recommendations, but the study in 2010 verified that this is actually a good course to take. So what it is is that patients should get, first of all, a baseline testing right before or right after starting Plaquenel. And then annual screening beginning no later than five years after starting the Plaquenel. And there are three things that need to be done. And first is the fundus examination. And that's not because it's sensitive to picking up toxicity, but it's to rule out and to make sure that there's not already retinal toxicity before beginning treatment. A tend to automated field must be done. And then at least one of these following objective tests, a multifocal ERG, a fundus autofluorescence, or a spectral domain OCT. And then the American College of Rheumatology in 2012 came out and supported these recommendations. They only added that they should get annual examinations before five years if they're in a high risk category, which would be, again, if they've already had more than 1,000 grams cumulative dose, or if they are on more than 6.5 milligrams per kilogram per day. So one of the things that they added was emphasis on counseling. So patients need to be aware that they cannot completely prevent retinotex toxicity if they're on plaque when they can only mitigate the damage. They also talk a lot about overdose precautions. They talk about four patient types. The first one is the patient with short stature, where the typical dose is too high. So the typical dose is 400 milligrams. And in our patient, 200, sorry, 400 milligrams, which is the typical dose, would put her at 12 milligrams per kilogram today, which is way too much. So, and then the other problem is that obese patients are often dosed on weight, which should not be done because the hydroxychloroquine is not retaining fatty tissues and so they can be overdosed as well. They should be based on ideal body weight. And then also patients with liver and renal disease need to be watched as plaque when ill is eliminated both through the liver and kidneys. So, here is an example that's taken just right out of the recommendations and what it's showing is how these are, there are different sensitivities for these tests. These are all of the left eye and all the pictures are taken in 2009, except for the previous visual fields. And they point out that the visual fields from 2005 to 2008 were deemed insignificant, but they stress the point that there's any repeats of even any point defects that it should be considered significant and the patient needs to be counseled at that point about cost and benefit of their medication. And B, they show that the fundus photograph is completely normal and not sensitive at picking up any type of damage. The OCT shows some thinning of the retinal nerve fiber layer and then we have some autofluorants in that kind of bullseye maculopathy right here. And then in the multifocal ERG, you can see that there's pretty normal wavelengths around the periphery and in the very central, but paracentrally, they are a little bit diminished. So, you can pick one of three of these modalities. The sensitivity and specificity of each one of them has not been determined yet, but they are seen as equivalent at this point. So a reminder of our patient, her only abnormality, which we don't know for sure is real or not, is these areas of depression here on her multifocal ERG. You can kind of see it a little bit better even down in this picture too. And so our plan with her is that first of all, based on her stereotypical sequence of events, we diagnosed her with migraine with aura and we started her on baby aspirin as a prophylaxis and told her to continue her border therapy with ibuprofen and we had her get an MRI brain because she's never had headaches before and they just recently began. And then as far as her plaquinal monitoring goes, because of the unreliability of her multifocal ERG, we're gonna have her return in four months to repeat it. And then if the testing is normal, we will begin the annual testing as the recommendations say in three and a half years from now, which is five years from her start date. And we're gonna cancel this patient. She's someone who's really worried about losing her sight and we're just gonna have to continue to cancel her on the fact that we can try and prevent this from getting bad but you cannot prevent it from happening at all in the first place. So just really quick, where I left off, I kind of left on a melancholy note last time talking about the millions of slaves who've exited through Ghana, through the slave castles that are seen here but I just kind of wanted to quickly reverse this and talk about how far Ghana has come in just a short amount of time. They gained independence in 1957 in only 56 years. They've gained independence. They have free voting for everybody over 18. They have religious tolerance and they've recently moved from a lower income country to a middle income country. And just some hope for Africa in general. I know I'm passionate about it. I've lived there for a year so I can't help but be really connected with it. Time Magazine and Economist and there's a lot of books coming out about how well Africa is doing. They're still obviously having problems we're hearing about Kenya and there's a lot to be done but economic growth is rising and I believe six out of the 10 fastest growing economies in the world in the last decade have come out of Africa and investment in Africa has increased tenfold in the last decade. So I think it's an exciting time to see what's gonna be happening in Africa in the future to just give you a brighter outlook than last time. So many thanks to the Neuro Ophthalmology team. I learned so much on that rotation and special thanks to Abraham who's always reminding everybody to get their power bar and thanks to Jim here in the front for helping me get on to Axis and Donald Krill for all his photographs. Thanks for dad for coming to support me from the emergency department and thank you to Alicia. She, there was no spots for me when I first was trying to get into ophthalmology and she went to bat for me and I've been able to do all the rotations that I needed to so thank you very much and thank you to all of you. And here are my references. Any questions? Dr. Olson? So this is just not only for you but for in general. You know, as you read all the controversial articles that come sense these guidelines, so Judith and I've got Don here as well. My sense is that as you add a lot of them together there seems to be a little bit that sensitivity is possibly greatest The sense I get from this as you try to digest all the agreement. Yeah. The multifocal came out as it felt as though there were problems. Did you read the same one? That's probably true but they were cautious because it's not widely available. And the quality in many parts of the country is yet obvious. Because so many general ophthalmologists are doing the screening and they didn't, they were just being cautious about the recommendations. Essentially they would have to go to an active. But it's definitely a challenging problem. A different line is followed by some various types of sensitivity. We get all three with multifocal. Yeah, it would definitely be nice if they did, you know, do a bigger study that it became standardized with just one of those three tests so that when people are cross talking about this patient or that patient, there's a standard but we're just not there yet. It's the data's been coming slowly. And that's the difficulty of doing studies in. Right. It's hard to find. Right. There's no benefit. Any luck? Yeah, I didn't. Why do you censor the color test in this? It's easy enough to do. Yeah, and the most recent recommendations basically said that every other test you should not do. Aside from those ones recommended. I'm trying to pull it up again. I just, yeah, the inner and outer layers, the separation disappears there and thins out.