 Thank you, Dan, for the mood lighting. Welcome to Grand Rounds. Today we have the Williams Brothers presenting. First will be Lloyd Williams. He has a patient presentation, a 78-year-old male with an intraocular mass. Our second presenter is Bryce Williams. He is presenting, Is It a Third and Early Worsening of Diabetic Retinopathy? All righty. Good morning, everybody. Dr. Bernstein asked me to present this guy yesterday. So sorry about the short notice. Hopefully, everybody had a chance to see him. He's a 78-year-old male extended to the VA with a complaint of floaters beginning three weeks ago and a new brownish discoloration in his superior temporal visual field. He also, of note, has a history of having a skin melanoma on his right cheek, a family history with melanoma, and one with macular degeneration, and a pastocular history that includes IOLs in both eyes and an inferior temporal nevus in his right eye, which was followed by optometry at the VA. And he was last seen by them in 2006. And at that time, the nevus was noted to be two disc diopters by two disc diopters and flat. So when he presented to us on Friday, the, sorry, this is not working. And this is the lesion we saw. It was a relatively large, darkly pigmented lesion with surrounding retinal detachment that appeared serious. There were no regmetogenous aspects to it. There were no breaks seen in the retina either. And this is inforo, yeah. And it is located inforo nasally in the right eye. I also wanted to comment that the patient requested to be able to hear this talk. So he's in the room right here. So these are just some more pictures of the same lesion. As you can see, it's outside of the arcade and the macula is on. His vision was 2060 in that eye. Fluorescene angiogram was done yesterday in the retina clinic as well. And they had some difficulty focusing on both the retina and the lesion. So you're getting out of focus view of the lesion here. But you can see quite a few vessels coursing over the top of the lesion. And that's an earlier view. So, you know, it's not really a diagnostic dilemma like a lot of the things that we present. But it was something that Dr. Bernstein felt was an opportunity to discuss a very important ocular disease which also has some important systemic ramifications. So in terms of how do choroidal melanomas present, 41% have no signs and they're found incidentally on an exam either for a lesion in the same or other eye or just as part of a routine exam. The most common presenting symptom would be visual field defects or visual disturbances which is what this patient was experiencing as well as flashes and floaters is about 15%. So he had flashes and a visual field defect. 3% can have pain which occurs if the tumor invades into the nerves and about or a small percentage in this particular study by Abramson in 1992, one of the 193 patients presented with metastatic disease. From our standpoint, the signs of ocular melanoma, things we see when we look in, include often a darkly pigmented mass but not always darkly pigmented. In fact, they can have almost no pigment at all. There are sometimes overlying drusen, orange pigments or RPE changes. However, even the orange pigmentation can be associated with some benign tumors as well. So, you know, a darkly pigmented mass with orange pigment over the top is very suggestive of melanoma but it's not necessarily a guarantee. Antietumors can also have sentinel vessels that are seen on the sclera going into the tumor. An advanced tumor may present as a blind, painful eye with proptosis secondary to transcleral extension of the tumor into the orbit. And rarely it's possible to also have a melanoma that spreads diffusely in the coroid. These can be relatively difficult to diagnose because they don't have the characteristics that we're usually looking for. And these often result in a serious retinal detachment. So, when a patient presents with something that you think is likely to be a coroid or melanoma, it's important to do several tests. One is ultrasound. Although imaging modes such as CT and MRI exist, the ultrasound is still the best way to characterize the tumor in this case. A-scan ultrasound not a great photo but it shows initial high spike and then low to medium reflectivity in the tumor and then the second spike of course is the sclera. You can also sometimes see vascular pulsations as fine oscillations in the low to medium reflectivity spikes here. In addition, B-scan ultrasound is used to characterize the size, thickness, diameter of the tumor and help you with prognosis and with choosing appropriate modes of treatment. UBM can also be used to look to see if there is anterior extension of the tumor or some tumors can actually occur at or in the ciliary body. And so, UBM is a good modality for looking at tumors that are much more anterior than this particular patient. In addition to those, FA is commonly done and it will show vascularity in the lesion usually. It also tends to show late diffuse staining. A CT and MRI could be used. You can see these lesions on those two modalities but due to cost and lack of sensitivity, they would be impractical compared to ultrasound. But it would be potentially possible to pick up one of these lesions in the process of doing a CT scan for some other reason. So that might be one way that a patient could potentially present. In addition, if there were a non-pigmented lesion that you were very concerned about you could potentially do a biopsy. Unlike retinoblastoma, this is a tumor which is much less likely to have a transcleral escape secondary to a biopsy. Although the papers that I read recommended beginning treatment essentially immediately after the biopsy to prevent that. Another important factor is that the patient needs to be screened for metastasis which is, if present, an important factor in determining treatment. Most patients do not present with metastasis that can be detected at the time of their initial diagnosis. In the collaborative ocular melanoma study, publication number 23, only 1% had metastasis at presentation. The five-year cumulative rate, however, is 24%. And metastasis is, of course, the most feared complication of choroidal melanoma. Most metastasis, depending on the site, studied in this particular publication, ranging from 56% to 100% of metastasis occurred in the liver. Other sites can include skin, subcutaneous tissue, and lung. They recommended screening with liver function tests and in patients who had at least one abnormal liver function test, the sensitivity was 14% and the specificity was 92.3%. So that's a pretty excellent specificity, but the sensitivity is poor and there aren't really other practical good ways of screening. So it's still advocated that patients have liver function tests every six months to a year in order to screen for metastasis. The prognosis, a 10-year survival, depending on the study, ranges from roughly 50% to 70%. Concerning factors include large size, anterior location, if it has escaped the eye through transcleral extension, growth through Brooks membrane, which appears as a mushroom-shaped tumor, optic nerve extension, lack of pigmentation, increased vascularization and histologic features such as mitotic activity and cell type. And for the sake of time, sorry Dr. Mamo, so I'm not going to go through the histology. Potential treatments for corridor melanoma depend in part on the size of the melanoma. Most sources recommended enucleation for large tumors, although I have seen examples of proton being more gamma-knife being used on tumors greater than 10 millimeters in thickness and greater than 15 millimeters in diameter. In general, however, radiation is used in medium-sized tumors and in some cases can be vision sparing depending on the location of the tumor. So for example, a tumor in the macula or at and around the optic nerve is not likely to be, you're not likely to have a vision sparing outcome, but a peripheral tumor, you may actually get a good vision outcome through one of the radiation treatments. The most common would be sewing a plaque designed for the patient's particular tumor onto the outside of the eye and using that to deliver radiation. Proton beam is probably the second most published method that's limited by the need for a particle accelerator, which are rare in the United States. When I last looked it up, there were seven, there may be more now. Some other less commonly used techniques would be used for small tumors, such as laser photocrygulation and transpupillary thermotherapy. In the literature, there was no difference between using a radiation plaque or a nucleation in terms of survival or metastasis. Coridomelanoma is the most common primary ocular tumor, about six to eight in a million. It's slow growing. The prognosis in terms of survival is probably better than for say an advanced skin melanoma, but still in terms of ocular diseases is a very serious one. And the modality of treatment has not been shown to affect metastasis or survival, but the tumor volume and location and some of the other things I showed on the previous slide have been. And it's thought that perhaps the most important thing with regard to survival is whether or not it has metastasized and so even though less than one presented with already known metastasis, it's thought that the patients who go on to have metastasis even after treatment likely had them prior to treatment and so essentially the cat was already out of the bag. And these pictures just show a melanoma before and after treatment with a radiation plaque. And these are B-scan ultrasounds of a tumor before and after treatment. And these two come from a study I did with Jay Duker on this subject. Any questions? Yes, that's correct. Absolutely. But the carotidonevis was noted to be in the infronasal quadrant. So this patient actually has as I noted an interesting family history of five family members including one who died of a skin melanoma and it's thought and he also had some genetic testing done at the Huntsman which indicated that his family and himself were at increased risk for melanoma. It's thought that the genetics of skin melanomas and carotomelanomas are different. And so an increased risk of one is not necessarily an increased risk of the other. Just point out that a lot of those analyses can be common. Dr. Harry's gonna see him at 9.15. So I don't know the size. I would suspect it's medium and large. And interestingly too from the genetics standpoint some studies have shown that tumors that exhibit monosomy of chromosome three are much more likely to metastasize. And it's not known whether that information can yet be used in a meaningful way that would affect patient survival or treatment. Yeah. And the COMPS trial now actually has quite impressive numbers over 7,000 patients have been entered into the trial. So for something which is pretty rare that's a good number. Dr. Patel. Yeah, thanks for that input. Dr. Harry. And it can sometimes go from the eye to the skin too. That's in my reading that would be probably more common. Yeah, so he'll be referred on to Dr. Winwood. And we'll see. Yes. Thank you very much for coming in. Any questions?