 OK, good morning. Now all of our speakers are here. And we'll get started. This is UVI's Grand Rounds, and we chose to discuss the white dots in drums. Crystal, do you cause snowing like outside? It's really, that's one of our white dots in drums. But also, the white dots in drums are a collection of inflammatory cordyretin opthies that are actually quite confusing to ophthalmologists and retinas specialists. And UVI specialists alike. There's no better way to illustrate this than through case presentations. But I thought I would start with a little overview to see what we're getting into here. So the white dot dots in drums are a heterogeneous group of non-infectious coriorectal inflammatory disorders that have overlapping clinical features, which makes them somewhat confusing. They are characterized by multiple well-circumstried, whitish-yellowish legions at some point in time in their course. In the outer retina RPE coriorectal acerchloride, this is a list of the white dots in drums. So an example is birch-eyed retina cordopathy associated in myths, a photograph here. With all of these lists, we do keep lists in our heads when we look at patients to try to put them into a category. Sometimes it's useful to actually think of them in categories and in groups. So for example, the placoid lesions are illustrated by ampy, surpigeons coriopathy, relentless placoid coriorectal and persistent placoid maculopathy. The placoid kind of gives it away a little bit. This is an example of ampy. We can also think about them in the groups of the multifocal coriditic processing, such as multifocal coriditis and pan-EUVIs and PIC, which we will be discussing today, progressive sub-retinal fibrosis syndrome. And then there's a group that Don Gass had put together the azore complex characterized by multiple evinosis white dot syndrome, azore acute idiopathic blind spot syndrome, which may be part and parcel of the same type of syndrome. We need to keep in mind that there are many other things that can produce white dots in the retina, such as these infectious diseases, non-infectious diseases such as sarcoidosis or sympathetic abdominal. This is a patient with tuberculosis coriditis producing a white dot. And this is actually a patient with tuberculosis serpiginous-like coriditis that looks very much like serpiginous coridopathy that needs to be treated with anti-tuberculosis therapy initially. So the white dot syndromes have many shared features. Demographically, most of them are under the age of 50 with a couple of exceptions, such as bird shot and serpiginous. There is a female predominance in many of them. They present usually bilaterally, but sometimes very asymmetrically. Patients frequently will have photopsias, blurred vision, myctolopia, floaters, and visual field loss. And a blind spot enlargement is not uncommon. About half of the patients will have a viral program. This is particularly true of mutes, multifocal coriditis, and RB, and ampy. And as I mentioned to you before, they can be grouped together as gas did in the azore complex. Whether or not this really holds true in terms of pathogenesis remains to be seen. The pathogenesis is really unknown. We really do not know what caused it. Some have, there must be an automatic time, I apologize. There may be an infectious etiology, gases that hypothesize the viral etiology, or an autoimmune inflammatory process, occurring among patients with a common non-disease specific genetics, perhaps initiated by some insogenous trigger or drug or microbe. There is debate as to whether or not some of these represent a single disease or spectrum of single disease or distinct entities, but really the pathogenesis is unknown. We can't really comment on that. And then we also must differentiate these from neoplastic diseases such as mar and car. Autoimmunity does occur frequently in patients with white dots syndrome of syndromes, not only in the patients, but among first and second degree relatives, suggesting that an inherited type of immune dysregulation may be common among patients with white dots syndromes that predisposes to autoimmunity. Nevertheless, with the variable lesion morphology and evolution, these can be clinically subdivided into distinct entities due to their distinct natural history and their visual prognosis. This is extremely important in terms of disease specific indications for treatment, as we will see, and it's illustrated by the cases. The thing that has really revolutionized our ability to differentiate white dots syndromes is multimodal imaging, such as color photograph in this patient with mues, fluorescent angiography, ICG angiography, OCT, high definition OCT and OCT angiography, and fundus autofluorescence in this patient with surpiginous indicating an area of activity that coronal neobascularizations seen in this patient with inflammatory coronal neobascular membrane. The utility of multimodal imaging is extremely helpful diagnostically. There are certain patterns and type of vascular involvement that really help us in making the diagnosis clinically. More importantly, it gives us an idea of the structural abnormalities that are associated with decreased vision, including optic nerve inflammation, macrodema, retinal vasculitis, neurosensory retinal detachment, paroline vascular membrane, and then with the advent of high definition OCT, structural abnormalities in the outer retina that can be very subtle, that cannot be appreciated clinically, but are appreciated with multimodal imaging. Finally, multimodal imaging gives us an idea of the extent of active inflammation, which may not be readily apparent clinically. This certainly alters one's treatment threshold and offers us a very sensitive modality for monitoring treatment. So we're going to begin with Dr. Weiss, who's going to tell us about urgot retinocortopathy. So I'm presenting on bird shot. So just kind of a basic definition. It's a clinically distinct form of the white dot syndromes. It's predominantly among middle-aged women, white women of Northern European descent. So you get these characteristic bilateral hyperpigment and inflammatory lesions at the level of the RPE and the coroid. They emanate from the optic disc in a predominantly nasal and the radial pattern. Again, like most others, it's not an infectious cause, but a putative autoimmune mechanism because they're such a strong association with HL829 positivity so much so that I guess a lot of the people are doubtful of the diagnosis of patients through H29 negative. And then it's a predominantly ocular disease and otherwise healthy patients. So this is the research requirements for study. So patients are required to have bilateral disease with at least three peripapillary bird shot lesions. There's typically low-grade vitreous inflammatory reaction, which is less than two plus vitreous haze. And then it's also supported by the presence of HL829 rental vasculitis and cystoid macular dima. So you get a mild non-grain alumus erosoclitus, but this is a predominantly posterior disease. So again, low-grade vitritus, but the classic multiple post-equatorial ovoid cream-colored lesions that can range in size from 50 to 1,000 microns. You also get rental vasculicage and then there's notable absence of snowbanks and then perform your vasculatization.com. So this then segment well, but the differential diagnosis, like with all of these, it's important to exclude other kind of treatable causes. So infectious categories. So syphilis is one of the main things that you worry about, but also TB, histoplasmosis, and then dosage, and then non-infectious. This is also kind of a good age period for people to develop lymphoma. So another thing to think about there, but just can't kind of hinge the diagnosis just on the imaging alone. So this was a patient of Dr. Vitalis. She was a 16-and-one-year-old woman that was initially seen in an outside hospital. She had complained of about a year and a half of just kind of decreased vision, nyctalopia, and bloaters. She was referred to him. Her vision was actually good. She had, I think, she was at 2040 when he initially saw her, normal pressure, just very mild AC cell, a little bit of vitreous cell. And then peripheral exam showed no snowballs, no snow making or anything. And then you can kind of make it out here, but you start to see these kind of creamy lesions here. So this is just a close-up of some of those that you're able to see. So I'm not quite as impressed with some of the other ones in the book, but it's still a good example. So like Dr. Vitalis was talking about the, kind of the new thing in UVI, this is more the imaging. So OCT is something that we're pretty much all able to get, and it's very useful. The characteristic findings with bird shutter, the macular edema, and it's also useful not only for following the response to treatment in terms of the macular edema. So on this top OCT you see the cysts there which have responded after treatment, plus systemically and locally. But you can also monitor the ISOS junction and for other changes in the outer retina that can reflect the visual function. Over time, if it's poorly treated, it can show macular atrophy. Then one of the newer things that's coming out is with the enhanced OCT, they're starting to comment on some kind of hypofluorescent areas in the choroid, which might be predictive of development of macular edema as well. Fundus autofluorescence is something, I don't know, I feel like we get it a lot. I don't know how to interpret it, but it can be useful for identifying other lesions that aren't clinically apparent. This was a picture from one of Dr. Spade's papers on using fundus autofluorescence. So you can see the white dots pretty prominently in the infronasal periphery. And there's a suggestion of some sort of macular changes, but they show up quite well actually on the fundus autofluorescence. So it can also be useful for delineating other areas of involvement. Fluorescent angiography is useful, but not in the sense that you'd always think. It's kind of interesting because the bird shot lesions aren't very characteristic on the FAA. They can mask early fibroids and some stain lane, they can show different patterns, but they're not classically thought of as showing up on the FAA. One of the main utilities is for identifying vascular leakage of macular edema. So this is just kind of a mid phase or sort of a little bit later phase, just showing some segmental perifluoritis and then angiographic evidence of macular edema. So this is that same patient of Dr. Vitali's and the other eye. So just the regular color fundus photo can't really appreciate the peripheral lesions quite as much on this little image here, but you're not really seeing too much in terms of the peripheral stuff on that fluorescent angiography. You do see a little bit of leakage of the disc and then just very early segmental perifluoritis. So you get vasculitis, which prominently involves the vein, veinules rather than the arterials. And then later you start to develop more angiographic evidence of macular edema. ICG and geography is kind of one of the more helpful tests that we have. They show well-delineated hypofluorosicroidal lesions that are more prominent in the mid and late phases of the test. You can also see some fuzzy appearing caroidal vessels as well, kind of indicating that with the retinal and the caroidal involvement of the disease. This is just a mid phase of the ICG. So you see these multiple kind of hypofluorosicroidal spots. And then in the, this is just kind of comparing that to that same picture as previously. So see more macular involvement here on the ICG and geography than you do clinically as well. So that's kind of one of the useful portions of this test. And then just in the later phase they show up even better. Electrophysiological testing is also quite useful. Classically it shows a preserved, virtual shows a preserved A wave. The B wave amplitude is reduced and there's increased latency time. With the, and then the other characters you find is a prolonged 30 hertz flick or implicit time. This one doesn't, didn't show it quite as well as some of the other ones. And I just couldn't find a good picture of a ERG that showed it. But this was Dr. Vitale's patient as well. You can also get elevation of the dark adaptation thresholds. But one of the useful things with the electrophysiological testing is that this and the visual fields can actually show improvement after immunomodulatory therapy. So it's useful one for making the diagnosis, but also for monitoring the response to treatment. And so the basic goal of treatment is aimed at preventing global retinal dysfunction. So as you can tell from the electrorenogram and just clinically that this involves the entire mac, or the entire retina, not just the central macula. This, kind of the point that Dr. Vitale was wanting me to make with this was that this is a disease where prompt systemic treatment is very helpful in the long term. It classically begins with oral steroids, which are used as an abridging rule while you're starting immunosuppressant therapy. So usually begin with an anti-metabolite, so things like methotrexate, cell-ceftor, imurium. And then depending on the clinical response, you can add a calcineurin inhibitor like cyclosporine or tachylinus. Failing this, you can also advance to biologic therapy, so things like humera or remicade. And then registered has been a useful tool and the patient's not tolerating systemic therapy. This was a patient of Dr. Shakur's that I wasn't able to get the rest of the pictures loaded up, but this was a person that came to him after a diagnosis of birdshot about 10 years prior, had not ever been treated systemically only with local injections of steroids through either intravitural or subtenon skinologue. So you can see the classic birdshot lesions, and then there's also a lot of kind of macular atrophy centrally. This is their OCT, so you've totally lost your outer retina detail, it's not showing up, just kind of diffuse macular thinning and loss of the ISOS junctions throughout. So you've lost your photoreceptors in this case, and so it's not conducive to vision. And this is the ERG late, so it's just totally flat and then just reflexive global retinal dysfunction. So that was my stuff on birdshot. Do we have any questions? We see a lot of birdshot here. We really do, it's a rare disease, about 7% of posterior uveotics, but we see a lot of Northern Europe. I think that the last case dramatically illustrates the need for kind of pulmonary therapy in these patients, local therapy. You can be fooled into thinking that you're treating them at your DEMA and there's no legal indices for inflammation like anxious segment cell or heavy vitritus just are not prominent in patients with birdshot. But as this graph illustrates, there's global retinal dysfunction. And if you treat just episodically with periopterous steroids or even, of course, system corticosteroids, you have a stepwise decremented function of the retina. So the problem is when do you start treatment and how do you convince the patient with good vision that they're gonna treat? So the natural history studies suggest that 85% of patients do poorly on monotherapy with corticosteroids. There probably are some patients that do well, but it's impossible to identify who those people are. So in patients that come in that are symptomatic that have structural abnormalities like macrogeema or retinal vasculitis, which is difficult to actually appreciate clinically sometimes, but was as recent showed, we could see promptly with whitefield forcing in geography, those are indices of active inflammation. And frequently patients will come in with visual field changes or abnormalities in their electorettograms. So those would be indications for treatment, even patients with relatively good vision. So we need to kind of convince the patient that it's in their best interest in the long run to be treated with immunomodulation. And I think that for people that are familiar with using that medication, that patients should actually be able to do that. I have two other thoughts on this in part, it's from a meeting we recently had at AUS, but with birdshot, following visual acuity is about, is as helpful as following visual acuity in glaucoma. So central visual acuity for an indices of birdshot activities just not helpful at all. And on the flip side of that, patients' symptoms and complaints can be very helpful. So they'll tell you, having some weird photopsias or decreased contrast sensitivity in birdshot, especially at something very important to listen to as a sign of activity. That's a very good point. And I have visual acuity is a terrible marker for following patients. That's why we use visual fields and ERG. And the patients really do have these peculiar, sometimes the patients are peculiar, and they also have peculiar complaints. But you really, like William Osler said, listen to your patients, they'll tell you what's going on with them, they'll tell you what their disease is, and it's particularly true for a child. So thanks very much.