 I'm going to introduce Andrew Nelson. He comes to us from the Keck School of Medicine at USC. And quite a nice transition from our last talk to discuss our carotid metastasis. So turn it over to you. Thanks. So as Dr. Jardy mentioned, I'm Andrew Nelson coming from USC. I'm going to be talking about diagnosis and management of carotid metastasis. And I'd like to thank Dr. Shakur for helping me select this topic and prepare this presentation. I'll actually end up citing some of Dr. Welsh's work. So hopefully this isn't too redundant, but hopefully we can consolidate some of what we just learned. So I'll be talking about how to differentiate carotid metastasis from other carotid tumors. And then we'll discuss the epidemiology and the roles of systemic and local therapy in managing this disease. So we'll start out with a case. This is a 62-year-old female in history who recently diagnosed stage 4 lung adenocarcinoma, presenting with two weeks of progressively blurry vision in the left eye. She notes that the blurriness is more concentrated temporarily and also endorses headache and photophobia for two weeks. Her past medical history is relatively non-contributory. She has history of myopia in both eyes status post-lasic in 2003. On examination, visual acuity in the right eye is 2040 minus 2, pinholing to 2020 minus 2. In the left eye is 2200, pinholing to 2060. And she has an afferent pupillary defect in the left eye. Examination is otherwise unremarkable. Slit-lamp examination is unremarkable, apart from trace cortical cataracts in both eyes. And on funnest exam, you can see that in the right eye, there are these two sort of yellowish pale lesions in the core right. In the right eye, along the temporal, the superior arcade, as well as supral nasal to the disc. In the left eye, there's this very large elevated lesion involving the optic nerve and the phobia, with some possible subretinal fluid gathering inferiorly. So here's the OCT of that left eye. You can see elevation of the core right with compression of the overlying coreocapillaris, as well as the presence of subretinal fluid under the phobia, and some small pockets of intra-retinal fluid as well. On ultrasound on B-scan, you can see the lesion here in the posterior pole has sort of a plateau shape. It's about 11 millimeters in width, and about 1.5 millimeters in height. And on A-scan, it appears to have a high to moderate internal reflectivity. So the differential diagnosis here for a caroidal amelanotic lesion would be essentially any type of caroidal tumor. However, given that this patient has a recent diagnosis of lung cancer, caroidal metastasis would be eyes on the differential. And then there are, excuse me, there are also some imaging findings which can help us differentiate a caroidal metastasis from other caroidal tumors. So the first thing is that in the right eye, we see these two lesions which are potentially also tumors. We learned later that they do also represent tumors. And metastases can potentially present as multifocal or bilateral, whereas other primary caroidal tumors are generally in the same one location. On OCT, the presence of subretinal fluid is the most sensitive and specific finding in caroidal metastases compared to other caroidal tumors. Something you might also see in a caroidal metastasis is a lumpy-bumpy appearance. And we don't really see it here. It looks pretty smooth. Some other potential findings are hyperreflective dots in the subretinal fluid or shaggy-looking photoreceptors. And we don't really see that here either. On B-scan, the best way to differentiate a caroidal metastasis from a caroidal melanoma is the height-to-base ratio. So a caroidal metastasis will tend to undergo expansile growth along the corollary, and it'll have a height-to-base ratio of roughly 0.2. This one here is about 0.15. Whereas caroidal melanomas tend to invade anteriorly through an intact brux membrane. So they have more of a dome shape, and the height-to-base ratio is generally around 0.6. And then on A-scan, caroidal metastases tend to organize into sort of glandular-like structures internally, which are echogenic. And so they have more of a moderate to high internal reflectivity. Whereas caroidal melanomas, as we learn, can be hollow in the middle with necrotic areas. And so they generally have a low internal reflectivity. So a few things about epidemiology. Caroidal or uveal metastasis are the most common overall intraocular tumor in adults. And in postmortem studies, they've actually been shown to be present in anywhere from four to 10% of patients who died of cancer. The incidence of diagnosis of patients living with cancer is lower at about 2%. And so this indicates that a large proportion of patients are asymptomatic and likely go undiagnosed during their lifetime. As we learned, up to 1 third of cases have no known primary cancer at the time of diagnosis. And so in those cases, systemic workup with likely a PET CT would be indicated to identify the tissue of origin. And in cases where that's inconclusive, the final aspiration biopsy of the caroidal metastasis may be indicated. So as we learn, breast cancer is the most common primary tumor of origin. This is the overall incidence. In women, it's as high as 90%. Lumb cancer is the second most common. And then other types of cancer are generally much less common. But any tumor which has the potential to undergo hematogenous spread can show up in the caroid. As far as the ocular sites of metastasis, the caroid is by far the most common site. And this likely has to do with its rich vascularity, as well as potentially having a supportive microenvironment for the growth of metastatic cells. So at time of diagnosis with caroidal metastasis, about 70% of patients have blurred vision, and they may have metamorphopsy of the phobias involved as well. They may also have visual field defects or flashes and floaters if there's an associated retinal detachment. And exudative retinal detachment secondary to the accumulation of sub-retinal fluid would be the most common complication of a carotomatastasis. There's also the potential for local invasion into the optic nerve, as well as BRCC's membrane rupture, which would result in sort of a mushroom-shaped appearance on fendoscopy. But this is much more common in carotomelanoma than in carotomatastasis. So any patient with a multi-metastatic cancer would generally require systemic chemotherapy. And carotomatastasis have actually been shown to regress with systemic therapy alone in about two-thirds of cases. And there are many targeted therapies now, which are very widely used, which target different tumor genotypes. In lung cancer specifically, we see like EGFR positive cancer can be targeted at these tyrosine kinase inhibitors. And they're generally used as either adjuvant therapies or maintenance therapies in between regimens of systemic chemotherapy. Local therapy is also used generally in conjunction with systemic therapy because it's been shown to improve response rates and reduce recurrence rates. And then external beam radiation therapy is the most common and most best-studied method of local therapy. It's been proven to improve visual acuity outcomes in patients with carotomatastasis. And it also reduces exudation, however, it generally takes a few months to have full effect. Photodynamic therapy is something that ophthalmologists can do, which produces a more rapid improvement in visual acuity. And it also is very useful in the foveas involved. Intervitrial anti-vegeth injections produce regression of the carotomatastasis as well as reducing exudation and has the lowest incidence of treatment-related complications. So this has a prominent or a promising future as well. However, there are no randomized controlled trials which compare these different local therapies with each other. And so selection of the appropriate local therapy for a patient really requires careful consideration of their structural involvement, their prognosis and their quality of life goals. So going back to our case, our patient was found to have an EGFR positive lung cancer with metastases in the liver, bone, brain and coroid. She received systemic chemotherapy with whole brain radiation therapy as well and received maintenance or latinib, which is a targeted therapy for EGFR positive lung cancer. This is what she looks like now, which is three years after diagnosis. So those two lesions in the right eye, which didn't turn out to be tumors, have apparently regressed. And then on the left eye, that large lesion is now totally flat and atrophic. This is what her OCT looks like and there's no more sub-retinal fluid or intra-retinal fluid or coroidal elevation. We just see some residual coroidal compression and hyperreflectivity in that area where the lesion used to be. So very briefly, this is another case of a patient with the same disease, EGFR positive lung cancer, presenting with a much worse prognosis and a complete retinal detachment in his right eye. You can see the retina positioned all the way anteriorly against the lens here. Unfortunately, this patient did not respond to therapy and ended up passing away slightly after these were taken. So this just illustrates the point that the response of coroidal metastases to therapy often parallel the response of a patient's systemic disease. So here are my references. Thank you very much.