 Okay. So, as Grant said, I'm going to be talking about PDT. So, it's a pretty big topic. And so what I was going to do today is just go over an introduction to what PDT is and then talk about one specific newer treatment on the horizons for PDT in a Crooidal Metastatic disease. So, I figured I would always start with some early morning humor. So, this is some different opinions about what grand rounds might mean, some different people. And on the other side, the Arnold's have feigned death and I hope none of you feigned death to get out of my presentation here. All right. So, what is PDT? So, in ophthalmology, we use verdiporphin. There are different kinds of molecules that are used, but verdiporphin is most applicable to ophthalmology. And there are some other kinds too, but this is definitely the most mainstream. So, it's referred to as a photosensitizer. And I think a picture is worth a thousand words. So, basically, the photosensitizer is injected into the venous system and then some time is allowed to pass and then light is applied intraocularly or actually to any area of the body where you can apply light. And it activates the substance or the verdiporphin at the specific wavelength and at the very specific location of the light. So, for verdiporphin, it's maximal activations at 689 nanometers. So, that's where you'll see that exact laser, the diode laser, being applied to activate verdiporphin. And what's really great about it is that exactly where the light is directed is the only place where the verdiporphin is activated. So, it's really great for targeting all sorts of localized pathology. So, you can kind of imagine that would be pretty applicable to ocular conditions. So, the 90s is when they started studying it in ocular conditions and they looked at it in some monkey studies because it was showing great promise for neovascular tissue, that it was able to specifically target neovascular tissue. So, they found in those early studies that it was really minimally disruptive to the surrounding environment, like the overlying retinal vessels or the coital vessels underneath. So, after that point there was a formation of something called the TAP study group and that was directed at age-related macular degeneration. And that was a series of multiple studies which had really served as the pioneer for PDT. And they really set the standards as to how we use PDT today. And it led to FDA approval for CNV secondary 2, AMD Pathologic Myopia and presumed ocular histoplasmosis syndrome. So, how does it perform specifically? So, I just wanted to show you kind of there's a very specific regimen. But what's interesting about the way that it's performed is that this is the original protocol that was set out by the TAP researchers. But lots of people recently have been varying this protocol and looking at how that might change outcomes and how things like concentration inside of the tumor are affected by a bolus infusion versus over 10 minutes. So, they've actually adjusted almost every parameter on this list here. And they've had interesting results in various kinds of ocular pathology. So, here's a list of tumors that it's used to treat in the intraocular tumors. So, today I'm just going to be talking about caroidal metastatic disease. But you can see there's quite a few others that it's been studied in. And especially with a large degree of success with the caroidal hemangiomas. So, just briefly I wanted to touch on caroidal metastatic disease. So, the UVL tract is the most common site for ocular malignant adult cancer. And it's thought to be because of the microenvironment and also because of the highly vascular nature of the UVL tract. Specifically, the coroid comprises the vast majority of the metastatic disease. The rest of the UVL tract is just a tiny percentage. And the vast majority of metastatic disease to the UVL tract is going to come from breast and lung adenocarcinoma. In fact, it's somewhere between 2 and 9 percent of all breast and lung adenocarcinoma that's going to metastasize to the UVL tract. And actually within that it's more breast cancer because it has better prognosis and longer survival, better treatments. So, more people are presenting with metastatic disease at this time, whereas lung adenocarcinoma has poorer outcomes. But even so, upon presentation with caroidal metastatic disease, the median life expectancy is between 6 and 9 months. So what we're really talking about here in this application of photodynamic therapy is palliative care and vision sparing care so that somebody doesn't have to go through loss of vision on top of having a very poor prognosis at the end of their life. So clinically what you'd be looking for is sudden vision change, blurred vision, scotoma, and pain. And I'm specifically highlighting pain here because pain is not necessarily a feature of other malignant ocular tumors. So whereas in metastatic disease, a moderate amount of patients present with pain as a chief complaint. But the vast majority actually present in the asymptomatic state. So this would be a patient who presents with a history of malignancy who's then coming in for screening who's found to have an asymptomatic lesion. But once these lesions are found, clinically they are very rapidly progressive. And they're aggressive, they lead to serious retinal detachments and they can involve the maculomphobia and involve central vision quickly. So you can see on exam here, the flat, they can either be flat or plateau in shape. And you can see the cream colored versus yellow on the in the lesions here. And then some element of serious retinal detachment on the right on the left side of picture. So why is PDT, why has PDT been considered for treatment of coroidal meds? So basically the gold standard of the most common treatment modality uses external beam radiotherapy. But as you can imagine, there might be some patients who aren't eligible for that. And there have been documented cases of patients who have chemotherapy resistant cancers. So they wouldn't be eligible for further chemotherapy to treat ocular metastasis. And, you know, people who aren't eligible for external beam radiotherapy might be individuals who are at high risk for post radiation retinopathy or post radiation neuropathy. So in individuals such as those, they have looked into other means and that's when PDT kind of came onto the horizons. And it's really it's it has favorable use because it's side effects are really minimal. Most of its side effects just comprise skin sensitivity and eyesight sensitivity to light. So for about six weeks after therapy, so it's a pretty benign treatment. So here's just some reports of there's actually only been four cases in the literature that have been described as of right now for Coroidal metastasis with PDT treatment. And they've been in two lung one, excuse me, one long two breast and one carcinoid that that were metastatic to the Coroid. And there was a very nice common theme between all four studies showing tumor aggression or stabilization and resolution of the serious or exited detachments, improvement in vision, and then a very dramatic decrease in neovascularization. But certainly one of the biggest limitations as I kind of already stated is going to be follow up. Since we already know the median survival is so low, it's so hard to study this in people who have this advanced disease who aren't going to be around for follow up to really see what happens to these lesions. So I just wanted to end with a few pictures here. So up top, the fun this photo is showing again that Coroidal lesion. Here's fluorescent angiography and you can see some pinpoint leaking. And then you have a B mode ultrasound where you can actually see the thickening of the Coroid and then the increased or the irregular reflectivity beneath. And then this is a indocyanin green angiography showing the neovascularization there in the preop state. And then I wish this OCT was a little bit better because you can kind of make out the line there showing the tumor underneath number one and then there's an element of serious detachment. So post op. So this is six months and we're talking about a very aggressive lesion. So this is approximately the same size. It certainly hasn't disappeared but its margins haven't increased and it certainly looks a lot cleaner as far as exudates go. But this one I think is really tells a lot about you can absolutely see this in comparison to the other B mode ultrasound the flattening of the lesion. And then again here on OCT you can see again a pretty dramatic reduction in the lesion size and resolution of the serious detachment and probably the most dramatic of all is the decrease in neovascularization seen on ICGA. So this is just another study. This was a breast cancer that was metastatic and again look at the dramatic changes between the pre procedure and post procedure states with quite a bit of leakage seen on fluorescein and dramatic reduction in post op and then probably sub retinal or near RPE and intra retinal fluid accumulation and resolution and restoration of the fovea architecture after. And then this is just showing very dense macular thickening right there and then post procedure it's returned to thinner level. So so I just wanted to kind of give a brief introduction to this and I think I'm probably out of time. So these are my references and I'd be happy to take any questions. Thank you. So there has been from what from what I've read actually more studies recently combining therapies. So nothing on our next presenter actually I think is Ed right at Stevenson. Ed is originally from Ogden and is currently in school at the Midwestern University in Arizona and he'll be talking this morning about optic atrophy.