 Marissa, you guys fellas are going to dazzle us with a little news. Good morning. So I'll be covering more than you ever wanted to know about dots and spots in the retina, and we'll start with the case. So this is a 38-year-old healthy Caucasian female that came in complaining of gray spots and the vision of her left eye starting three days before, accompanied by some intermittent flashes and shimmering of the vision of the left eye. She was a fairly high mile with no past medical history, but she did have several first-degree relatives with autoimmune disorders. And she was a physician, but otherwise unremarkable social history. On presentation of the UBIIDIS Clinic, vision on the right eye was 2020. Left eye was 2050. She was seen a few days before on-call and the left vision was 2030 at that time, so it had declined a little bit in the past few days. Vision, or sorry, pupils and pressures were normal. Antir segment was unremarkable. She was noted to have rare vitreous cell in the left eye, but no haze. Fundus photo of the right eye, a little bit of myopic changes, but otherwise unremarkable. And fundus photo of the left eye showing some punctate, whitish-yellow lesions in the posterior pole. So the differential at this point, just based on the fundus appearance, is still quite broad. We don't know what the course of the disease is. Is it going to occur in the other eye? If there's any systemic involvement or if she has any infectious exposures. So at this point, there's autoimmune or inflammatory conditions. Always think about infectious disorders. And we're going to use multimodal imaging to further characterize this condition. This is fundus autofluorescence, so we can see hyper-autofluorescence in the peripapillary region with some punctate appearance extending beyond. OCT through the fovea shows some hyper-reflective material at the ellipsoid zone, sub-fovially with protruding into the middle layers of the retina. And also towards the left of this image, which is nasally, there's a more diffused disruption of the ellipsoid zone. And then OCT just superior to the fovea, there's more irregularity of the photoreceptors. This is early fluorescent angiography at about 30 seconds, and we can start to see some hyper-fluorescence in the peripapillary region, which becomes more intense in the later frames. And then if we zoom in on one area, and I apologize because the image quality degrades, but you can imagine that the hyper-fluorescence is sort of a ring-shaped pattern right here. This is midphase ICG, and there's some hypocyanoscent lesions in the posterior pole, but not too remarkable. But then late ICG, many more hypocyanoscent lesions cluster around the nerve, which is many more than we saw on exam or on fluorescent angiography. So we tested for all the usual suspects, and that was unrevealing. We did start oral steroids in this patient, and she had a little bit of decline in vision since the initial presentation. And she was already on Valtrex TID when she got to us. There's some anecdotal reports in the literature of the rapid response of vision after starting antivirals and the azor-like illnesses. We continued that. Two weeks later, and she had an entirely sort of resolution of those lesions that we saw in the posterior pole. The lesions were evanescent. Vision at that time was 20-30. But her autoswarsons was still markedly abnormal, actually a little worse. She had some restoration of her ISOS junction, but not completely back to normal. So based on the clinical course and the appearance, we feel this is a pretty classic case of multiple evanescent white dot syndrome or mutes. This was first described by Lee Jampol in the 1980s. He had 11 young female patients with transient vision loss in one eye with some white dots in the fundus and they recovered without treatment. As Dr. Vitale mentioned, the exact etiology of these white dot syndromes is unknown, but there's some suggestion of an infectious etiology about half the patients to have a viral prodrome. They may be exposed to an exogenous agent that then stimulates an inflammatory response. And as mentioned, there's a higher prevalence of autoimmune disorders in patients that are relative, suggesting an inherited immune dysregulation. Average age is 28 years, there's a female predominance, and it does occur in all races. So clinically, patients complain about blurred vision, so potopsias or shimmering of a vision in floaters, usually in just one eye. They may have a viral prodrome. On exam, we see these small yellow whitish 100 to 200 micron lesions with slightly indistinct borders that are clustered in the perifogreal region and around the optic nerve, but typically sparing the direct phobia. Each dot is composed of many smaller dots. Macular or phogel granularity is a hallmark of this disease. And you can have a little bit of anterior chamber reaction and a mild vitritis is seen in about 50% of patients. Optic dysphoenic is quite common. So it's typically thought of as unilateral and non-recurrent, but there are at least 22 reported cases of bilateral involvement and more than 10 of recurrence or chronicity. So this disease has a natural good prognosis with restoration of the vision back to baseline usually within 4 to 8 weeks without treatment. And the lesions resolve on exam with restoration of the visual acuity. So back to the dots and spots. This is something that GAS described seeing on FA and ICG. Phonics that are seen in some but not all cases. And the dots correspond to those white spots we see in the posterior pole. These are smaller and more superficial located in the outer nuclear layer. And then spots are larger and deeper in the ellipsoid layer. So on OCT there's irregularity or debris of hyperreflective material at the ellipsoid layer corresponding to the dots. Kind of a buzz phrase is hyperreflective material resting on the RPE. And then the protrusions of this material in towards the middle retinal layers is responsible for the dots that we see. And here's photos describing it from the literature seeing these protrusions up into the middle retinal layers. And here as well. And you notice that the RPE is usually intact and that the hyperreflective material is accumulating on top of the RPE which distinguishes this from the choice presentation of PIC and multi-pocal where the hyperreflective material usually accumulates under the RPE. There's varying reports in the literature about the fundus autofluorescence being either hyper or hypo autofluorescence for the dots in the spot scene but in this reminder of what the autofluorescence looked like in our case so there is no hypo autofluorescence. And then fluorescent angiography the classic teaching or the early punctate hyperfluorescence corresponds to a resalite configuration and there's some peripapillary staining late. This is a classic photo showing the resalite configuration which we could kind of see in ours as well. And then on ICG late ICG which is a hallmark of this disease that there's many more hypocynesic lesions seen on ICG than either FAA or an exam. And they're clustered around the posterior pole corresponding to the area of visual and field defect. And there's dots and spots and dots on spots. And then putting it all together this is ANFOS OCT comparing the lesion on FAA and ICG with the layers of the retina showing that the dots are more superficial and the outer nuclear layer and that the spots are in the lipsoid zone. And then one of our more recent modalities of multimodal imaging is OCT angiography importantly showing that there's a completely normal coriocapillaris and coroid in this disease in all the patients in this study. So with our multimodal imaging it may not tell us why this disease has happened but it can tell us exactly where they're happening. So this is really a disease of the photoreceptor layers. Rather than the coroid. For visual field testing we have enlargement of the blind spot correlating to the hypocynesic lesions around the nerves seen on ICG. And the visual field defects can persist longer than the central visual acuity decline and after the lesions resolve. There's many people that suggest that the acute idiopathic blind spot syndrome or enlargement syndrome is really this disease or it's used as a waste basket term for mutes and azores and poorly understood entities that do have enlargement of the blind spot. If you get an ERG in the acute phase which can be difficult there's some abnormalities in the oscillatory potentials on full field ERG. And then multifocal ERG has been used extensively to try to map topographically the retina and the function. Understanding that the multifocal ERG response is measuring the outer and middle retina and the multifocal oscillatory potentials reflect the inner retina function. So knowing that there's a study that showed acute ERG or ERG in the acute phase of mutes and here's a multifocal ERG that's abnormal in the left eye which is the affected eye and here the normal right eye. And then they superimposed the multifocal ERG oscillatory potentials onto the multifocal ERG and it's showing that there's some retinal dysfunction on the oscillatory potentials even in areas of so-called normal retina which suggests that there's some inner retinal dysfunction that's preceding the outer retinal dysfunction in some areas. So back to our case. In six weeks patient's vision was back to 2020 in both eyes. She had a normalization of her fundus auto fluorescence appearance and restoration of her ellipsoid zone. She was tapered off her steroids and did well. Question. Have always been interested in potential infectious disease for distribution. When Lujan Paul first reported his cases they were all clustered in Chicago and at the same time we saw suburbs of Chicago cluster of big cases over less than a year very similar findings to what he had reported initially and then over the course of the next three years saw like one more case and so and they all had the same pattern that they would get the initial findings and then without treatment they would just fade away. They had maybe a few cells in the vitreous very vague and they had a big blind spot and all the other findings but we're always wondering if this was some kind of a close viral etiology and why would it cluster in these particular areas if it wasn't infectious. That's a really good point. I still don't think we know the answer to that and it's definitely a proposed theory. Phil, would you continue your patient on the antivirals? I think we stopped it after the 6th year that the 4 week appointment on the visuals. There have been some reports that antiviral therapy may be effective in ASR, which is another entity that there's overlap with views in ASR in so-called ASR complex but there are only a couple of case reports and I've actually not been too impressed with ASR. But Don Grass is a pretty smart guy and he postulated viral etiology to these diseases. I think it's certainly possible that a viral trigger is responsible for this. But Grass actually felt that the virus went into the photoreceptor layer and was actually primarily responsible for it. The more prevailing idea is that genetically predisposed individuals are exposed to a viral illness. It's a trigger for an immune response. It's fascinating the white dot syndromes are fascinating because of the variation in their severity and recovery. Are there any other questions about mutes? So I hope that we got a couple of take home messages. The white dot syndromes are interesting. We really don't know what causes them yet but we have learned a lot about them clinically over the years in terms of the clinical descriptions. It is possible to separate them clinically based on the clinical description and their natural history and more recently with the advent of multiple imaging particularly high-definition OCC and OCCA, we can characterize them better I think a viral illness. We can characterize them better. We are very confident about where the actual pathology is actually happening and this is particularly true in the case of Borissa just showed where it was previously thought that mutes was an inflammation of the cord capillaries that clearly shows it's a blood receptor disease. Ampere is another and serpiginous are also diseases that have multiple imaging particularly OCCA has shown that it is indeed probably a cord capillaries with secondary involvement of the retal pigment epithelium and where things are happening. The other thing is that reaching them, whether or not they're spectrum of the same disease I'm certainly open to that when we can figure out what causes many but I think it's really important clinically to distinguish them because they're definitely disease specific communication treatment so a patient with serpiginous or urchitis retreated with immunomodulation pretty much from the outset, a patient with immunostatic knee treatment so I'd be choosing units if I had a disease like this that could pick in multifocal corridors. The other real interesting utility I think and some of the difficulties we have sometimes in patients with multifocal corridors and pick is trying to distinguish between what is an inflammatory region in the retal pigment epithelium and what is an inflammatory cord that will be about to be a membrane and it's sometimes difficult to distinguish that based on of course these two two membranes they do leave so do inflammatory regions and I think that OCT angiography may help us in distinguishing that so thank you very much and I thank my presenters they did a great job