 which unfortunately happens to be the longest lecture of the whole series. So I'm gonna talk a lot about that today and I believe next week is orbit. And then it kind of starts going on to the center, so please look ahead at time and know what's to be expected. So the other tradition is, is you get the pleasure of seeing my travel slides. And historically what I've done is I've shown you slides from the previous ESCRS meeting, but because of the COVID and the fact that the ESCRS was a week before the AAO, I haven't been for three years. And so this is where ESCRS was this year. This is Milano. And unfortunately this was a decade ago. So this is the Duomo, the cathedral in the main square in Milano, inside of the cathedral. What's interesting is there are murals on the wall on both sides. Let's see if we've got, do we have our little player thing? Let's see if we've got our little player thing. Okay, so murals on both sides. Unfortunately the, people hasn't been spiffed up in a while, so it's really kind of hard to see them. But classic stained glass, vaulted ceilings. And this is some of the stained glass that you see. So we're gonna, this is one of the popes. Popes is buried here in Duomo in Milano. Okay, we're gonna talk about the retina. Now, when you talk about the retina, we wanna get a few definitions in there. And so from the pathologist, the definition of the macula is what? Startin' to swing around, more than one layer of ganglion. Exactly, so the pathologist's definition of the macula is more than one ganglion cell layer. But that pretty much matches up the retina doctor's definition of the macula, which is the area pretty much temporal to the disc within the arcades. And so when we look at the retina, the retina has, I can't say anything right, I'm just pointing. So, what do retinas and ogres and onions have in common? Layers. Layers. All right, so we're gonna start with the layers. And so, as a pathologist, I look at the retina this way. When you have the anatomists and the research guys do it, they do it upside down. So, you have to kind of turn your head when we do the lecture. So, these are the layers. This is the vitreous on top. This is the core rate of the bottom. So, we're gonna start going through the layers. So, this is the vitreous. What layer is this? Isle. Internal limiting membrane. Next layer. Inner fiber layer. Inner fiber layer. Next, I can't see a thing here. Next layer. Ganglion cell layer. Ganglion cell layer. Next, inner plexiform. Inner plexiform. Next. Next. Outer plexiform. Outer plexiform. Next. Outer plexiform. Outer nuclear. Okay, and these are our receptors, and this is our PE. What is this? Coriocampillaris. Then we've got medium and large vessels of the coroid. All right, so we're gonna start again at the top. Internal limiting membrane. What forms that? Hopefully, it's a new result. It's not really a membrane. It's the foot plates of the muller cells, okay? And then, what I wanna do, you know what? Let's do a little bit differently. Let's trace a photon of light. It's a little bit easier to kind of understand the anatomy if you understand what cells do what. So, photon of light goes through the vitreous all the way through the retina. It hits the outer segments of the photoreceptors. It hyperpolarizes the membrane and switches the retinol, switches from Cystitrans, and you start to get a signal, and it goes from these photoreceptors to this cell body right there. What cell body is that? Exactly, and it lives where? The outer nuclear layer. All right, so then that signal goes through the axons of this photoreceptor cell body, and it synapses with what cell right here? Bipolar cell. Bipolar cell. All right, and the bipolar cell lives in the... Internuclear layer. Internuclear layer. All right, so then that goes out the axon of the bipolar cell, and it synapses right here with what cell? Ganglion cell. Ganglion cell, all right? And that ganglion cell lives in the... Ganglion cell. Ganglion cell layer, good. And then the axon of the ganglion cell layer goes out. Alarna fell to the LGM. All right, and where does it pass through to get there? Alarna fell. Yep. So trace that axon from that ganglion cell to where it synapses again. Okay, but where does it go to get there? There, this far apart. All right, so it goes out through the optic nerve, all the way out through the chiasm, then all the way back and finally at the lateral geniculate body, it synapses. So that's an incredibly long axon. And what it does is it allows any place along that long tube that axon to be disrupted to eventually lead to atrophy of that ganglion. So it's a very, very long one. All right, now, there is a layer in here, the inner nuclear layer, which is a very busy layer. So we already said there are bipolar cells in there. What other cells live there? Let's name one. Emercant cell, another one. Sorry? Horizontal cells. And the last one? Neural cells. Neural cells, all right. So, emercant and horizontal cells are the first line of processing of an image in the retina. And so those think about them, they're like octopuses. They send their tentacles out and they're horizontally oriented. And so they already start to touch multiple other cells and they already start processing going on. So there's already visual processing going on right there. And then the Mueller cell, we already said it sends its little fibers all the way to the internal limiting membrane. So the Mueller cell is kind of the scavenger support cell, if you will, and it pretty much goes almost the whole width of the retina. Okay, so everybody comfortable with the layers? All right, where are we now? What part of the retina are we in now? Exactly, so you look at the ganglion cell there, ganglion cell layer is multiple cell layers thicker, so we know we're in the macula. Now, when we look at the center of the macula, what is this area called? The phobia, and so if you think about it, that's the part of the eye that gives you your fine vision and you don't want to have those light waves coming all the way through all those layers of the retina. So the way the retina is designed to avoid that is you see it thins out markedly here in the center of the phobia so that that light reflects, that light ray, I mean, come all the way in, get those photoreceptors here. Now, the center of the phobia is very, very cone rich and because you want fine vision, one cone links up with one horizontal cell which links up with one ganglion cell. So because of that, there's a lot of ganglion cells there so they get stacked up on the side there so these fibers as they come out start to run, not vertically, but start to run obliquely to link with those. Now it's different in the peripheral retina. The peripheral retina's purpose is to give you side vision and to give you movement and other things and so in the periphery of the retina, up to a hundred rods may be linked up to a single ganglion cell. What does that do? That gives you summation. So if you've ever been out on a dark night and you see, boy, there's a little straight line way over here and then you look at it, it disappears because the rods all gather that up and do that and so that's important evolutionary wise because if there's a sabertooth tiger sneaking up on you to eat you, you wanna be able to see that and so that's what the periphery does but in the center, you wanna be able to see your fine detail and that's why they're all stacked up there. So if you look right here, you see the fibers here in this layer run almost obliquely. What do we call that layer? Henle's layer, so Henle's layer runs obliquely. Why is that layer important in the area right next to the center of the phobia? Exactly, so that's where edema, cystoid macular edema starts up. All right, so let's talk a little bit about diseases that can affect the retina. So what do we see in here in this, from this photo? What do you think could cause this? Believe it or not, even diabetes can cause pictures like this, so believe it or not, this was a patient who came in and we looked at it and we did all that differential diagnosis and then interestingly enough, the student with me at that time said, what's the blood pressure? And we went, gee, I don't know. We searched the entire clinic, eventually we found one of those things that goes on your arm that measures blood pressure and we did it and this patient was 200 over 100, literally. So went right to the ER, this is severe hypertensive retinopathy. Now, sometimes it'll look a little bit different and good evening, all right, good timing. So, what do we see in right here? And you see, they call this a star shape, starfish shape and so that really kind of tracks along Henley's layers, so you get kind of that star shape looking to it and so this is again a severe hypertensive retinopathy. If you look carefully, you see that that disc, instead of looking that kind of yellowish light pink it's more red and so the vessels on that disc are more dilated and in severe hypertensive retinopathy, you can even get papillodema and severe disc changes. So if you look right here, again, this is a patient with severe hypertensive retinopathy and you can see in addition to the hemorrhages, you can also see exudates here and you see edema of the optic nerve and it's a severe hypertensive retinopathy. All right, what are we seeing right here? So what causes this? All right, so what gives us the cherry red spot? Why don't we see that? That's from the... Sure, I find some. Exactly. So it's kind of like a window showing you when you have a central retinal artery occlusion that coroidal blood flow is still intact. So in the center of the fovea where the retina is really thinned out in that area, you can still see normal coroidal blood flow showing through yet the rest of the retina is ischemic. It's white, it's pale. This is a central retinal artery occlusion. So what are we seeing right here? Exactly. So this is where not the central retinal artery but one of the main four branches of the central retinal artery has been included. Now, when we look at occlusion of a central retinal artery or just arterial occlusion in general, traumatic or embolic? Usually embolic. Usually embolic. And so when you see either central retinal artery occlusion or a branch artery occlusion, you really need to work up the patient carefully for a source of that. That could be a blood clot. It could be cholesterol plaque. It could be coming from the carotids. It could become from the aortic arch. It could be even coming from the heart itself or one of the valves in the heart. So very important that you work this up because if clots are going to the eye, they could be going to the brain and elsewhere. All right. What are we looking at right here? What is this? This is the central retinal artery. So what's going on with this central retinal artery? So way too many crown burgers and moochies here. So this is a good old American diet. You can see a ton of cholesterol, lipid. Look at that artery. It is markedly narrowed. And so you can imagine that would predispose that to either a blood clot or a little piece of cholesterol, something that would block that off. So this is where the central retinal artery and the central retinal vein come into the retina together in the optic nerve head. So the other thing I want you to see as you can see this very arteriosclerotic artery shares a common adventitial sheath with that vein. And so arteriosclerosis is the most common cause of central retinal artery occlusion. Also arteriosclerosis is the most common cause of central retinal vein occlusion because that artery kind of pushes on the vein next to the complete stasis of the vein occlusion. And what are we looking at right here? Looks like it's just swollen in a retina. Okay, care to rephrase. So it looks like the R-N-F-L is very swollen and retinal layers are kind of hard to differentiate. So I wouldn't use the word swollen. I would use the word absent. And so what you're seeing right here is you're not so much seeing swelling here. But look, that ganglion cell layer is pretty much gone. And you look at that big inner nuclear layer, all that's left is just the outer third of it. And so this shows nicely where the blood supply of the retina comes from. The outer retina gets its blood supply from the coroid, the outer third. So the outer nuclear layer and just part of the inner nuclear layer, they get their blood supply from the coroid. They're still intact. The inner two-thirds of the retina gets its blood supply from the central retinal artery. It's totally wiped out. And so in this part, I wouldn't use swollen. I would use absent. And so you're just looking at retina that's been wiped out the inner two-thirds from the central retinal artery occlusion. Question? Yes? Is there an exact layer where you can say the one-third starts with the two-thirds here? Not really. It's just it's a rough estimate because it's different in each person. But roughly you can say that about the outer third of the inner nuclear layer is from the coroid and the inner two-thirds is from the central retinal artery. Was it really? Yeah. Well, I'm glad. I think it's the outer nuclear layer is like the watershed layer. Yeah. So that's interesting how they do that on OCAPs because I find that OCAPs, they literally want to separate wheat from chaff. And so there's lots of chaff and not much wheat in people taking that exam. So they can ask some really obscure questions. All right, what are we seeing here? So I love that term blood and thunder. I don't know what that means, but I don't know what thunder means. There's a lot of blood. So blood and thunder, if you look, all four quadrants are affected. You see that the venials are really dilated here. There's blood everywhere. So central retinal vein inclusion. And again, we said that's caused by arteriosclerosis, causing stasis in that vein. So central vein inclusion. Central vein inclusion is thrombotic, not embolic. Now, what is this right here? I think it's a similar case, but you know what I'm saying. All right, so this is a branch retinal vein inclusion. And you can see a few little cotton wool spots on here. Now, where do those usually occur, those branch retinal vein inclusions? Exactly. So when you've got an arteriosclerotic arterial, and the vein crosses over at that thick, again, arteriosclerotic arterial presses on that vein, gives you stasis. And so oftentimes when you see these branch retinal vein inclusions, it's at a crossing point where the vein crosses over the arterial. And this is an eye cut in half, sagittally. And you can see hemorrhages from the optic nerve all the way to the aurocerot, all four quadrants, in central retinal vein inclusion. And now you can see, this is blood everywhere, and ischemic damage, because you do get ischemia, you get background damage to the retina diffusely from the central retinal vein inclusion. All right, what are we seeing here? So some of the things you can see are a lot of exotides, I'm not going to say this in some sense, and varying types of hemorrhages. There's several flame hemorrhages. So what's the difference? No, that was good. What gives you flame hemorrhages? What gives you dot hemorrhages? So much of hemorrhages. And then deeper, maybe like the dot hemorrhage. Okay, so if you think about it, remember that nerve fiber layer, it comes out and then it runs parallel to the surface of the retina. So if you get superficial hemorrhages, they spread out along that surface. And so we call these flame hemorrhages. Whereas if you get deeper hemorrhages, they tend to be more localized, and those will be the dot lot hemorrhages. And you know, we've got lots of exudates. What is this right here? Cotton wool spot. Cotton wool spot, all right? Let's keep going. What causes a cotton wool spot? Ischemia, I mean, it can be in fission, but certainly localized ischemia. But again, it's of the RNFL. So if you look at this, the reason people call them cotton wool spots, they look like little pieces of cotton kind of on the surface of the retina instead of deep inside the retina. All right, so we're looking at a special preparation of the vessels, the capillaries in the retina. What do we look at at right here? All right, so these little micro aneurysms, these are the first sign of diabetic damage to the retina. So the parasites tend to drop out. So when you get ischemia from diabetic retinopathy, the parasites are the first ones to drop out. And then the little capillary wall weakens and you get these little micro aneurysms starting to pooch out. And then you get leakage of blood and you also get exudate. And so this is exudate in the macula. Now this exudate tends to be very lipid rich. It tends to have a lot of yellow in it. And so you can see a lot of lipid here in the macula from the leakage. And this is what it looks like when you look at a pethanol. This is exudate right here. And so it's lipid rich, it's protein rich. It's just serum basically leaking out. Eventually a lot of the serum gets reabsorbed but a lot of the lipid leaves get left over. So this is hard exudate here in the retina, especially in the macula. Now what do we look at at right here? Some of your seven cotton spots. Exactly, so we're seeing lots of cotton oil spots. Again, they look very superficial. They look like fluffy pieces of cotton on the surface of the retina. And then we look at them and what are we seeing right here? Exactly, so this is caused by a focal ischemic, eventually infarct in the nerve fiber layer, the ganglion cell layer, the superficial retina. So you see this very, very swollen area. And if you look at this at higher power, these are ganglion cells here and they are very swollen from the ischemia. Now, once the ischemia kills those off, then what happens is the cotton oil spots go away. But if you were to track that, do a multifocal ERG, you could actually find areas where they've dropped out. So you can see swelling from the ischemia acutely and then eventually that goes down. So cotton oil spots, focal ischemia. What are we seeing right here? Exactly, so this is neovascularization where? Else, so it's funny that somebody was non-imaginative. So you have neovascularization of the disc and then the other 90% of the retina, if you call it NVE, neovascularization elsewhere. So this is neovascularization elsewhere. And then of course this is? Neovascularization of the disc. NVD, and so we call this the medusas, look. Remember medusa from mythology who had the snakes coming out of her head? That's what this looks like. You've got all these dilated vessels in the optic nerve head. Now, it's very interesting when people first got lasers. There was a xenon arc laser that came out in the 1970s and these things were amazing. They were like burn a hole through metal. It's very powerful laser. So people said, hey, why don't we treat these and shrink the blood vessels and cure neovascularization? So they took the xenon laser and they blasted the blood vessels right on the optic nerve head. Well, what that did is that caused huge loss of nerve fiber layer coming in and huge damage. But at the same time they found people with neovascularization elsewhere. They blasted it with a xenon laser. And what happened is not only would that neovascularization perfectly go away but on the central disc would go away. So what does that tell you about the cause of the neovascularization on the disc? Yeah, so it's from mediators put out by ischemia and that's the key thing. So VEGF is one of them. And so one of the things you can do is you can treat the peripheral retina with laser, decrease the load of ischemic factors coming out and the neovascularization goes away. Of course, now we've got anti-VEGF injections that we can do which again, decrease those blood vessels. And so it's chronic ischemia that causes the NVD of the disc. And what can happen if you don't treat this? Exactly, so hard to see where this is because of all the hemorrhage but this is along the arcade. So you can get not only chronic hemorrhage but you can get fibrosis. So you really want to treat the diabetic retinopathy before you get to some of these end stages. And of course the ultimate end stage of NVD is, all right, so what kind of hemorrhage is this? So it's a pre-retinal hemorrhage and when you've got a pre-retinal hemorrhage it's kind of between the surface of the retina and the vitreous, you get what's called a boat shape. And so you see it's flat on top and then it's kind of curved on the bottom so you get this pre-retinal boat shaped hemorrhage. So again, that's a sign of bleeding from neovascularization. So again, you want to try to prevent this from happening. What's another result of ischemia? You can get neovascularization of the iris and the ingus. So this is neovascularization that even an intern would recognize. So it's called rubeosoceridus or neovascularization. We used to call this ropeosis, you know, it's a group of blood vessels on there but the problem is, is if you let this neovascularization grow unchecked on the iris it can cause some issues. What are we seeing right here? All right, so you can see that that retinal pigment, I'm sorry, the iris pigment epithelium has been pulled around the corner and look at all those little blood vessels on the surface of the iris. And so as you get that neovascularization growing it contracts, it can pull the pigment epithelium of the iris around the corner. So you end up getting this picture. And what else can this do if you've got neovascularization in the iris? You can get PIS, you can close off the ankle, you can get lacyvaculization and thickening of the visumum. So what does PIS stand for? Perforolantereal scenicia. Exactly, so you get scenicia, you get iris sticking to the peripheral cornea and the anterior chamber angles clear back here. So you get blockage and then severe neovascular glaucoma if you don't treat this. And this is what you already said, as you get lacyvaculization of the pigment epithelium of the iris sticking to the diabetes. Does that represent a certain stage like the lacyvaculization? Yeah, that's usually a later stage. Like PDR. Yep, it's a very late stage where you've got significant proliferation. What else does diabetes do? So it causes a little thickening. And what stain is this? Acid. Okay, so I apologize for you guys. Normally I give you the basic lecture first. Sorry, but. So the PIS stain stands for basic membrane and this nicely shows that the basic membrane of the ciliary body gets thickened. Now I have to tell you the story if you guys have heard it, just roll your eyes. But those who haven't heard it. So when I was a pre-residency fellow doing ophthalmic pathology with Dave Apple, he said they want some slides to put on board. So pick out some good slides and send them to him. So pick out some good ones and send them to him. So I sent him this slide. And sure enough, when I took OCAPS as a senior resident, my slide was on there and I said, oh wow, thickened basement membrane, diabetes, man, this is great, I'm so smart. And then the question said, A, a patient with this picture would have a urinary creatinine clearance of, B, a perineal nerve velocity of, and so they love two part questions on OCAPS. You guys will hate that because you know it's diabetes, but okay, what is the creatinine clearance? You know it's decreased, but what is the number? What is the perineal nerve velocity? So even though it was my picture, I still don't think I got the question right. So I always remember diabetes, thickened ciliary body, basement membrane, and this can pop up occasionally. All right, what the heck is this? So these are laser spots. All right, so those are laser spots. So the idea again is we treat the peripheral retina to decrease the ischemic load to then make the neovascularization go away. You do not zap the vessels directly when you do this. Here's a laser spot. Now it's an argon laser usually. And what it does is it's absorbed by the RPE. You can see that in this laser spot, that RPE is just cooked. The toriel capillaris is sealed off. You get atrophy of the retina overlying it, and then of course you've got no more on both sides. So you decrease the load of ischemic retina and the periphery in order to save the center vision and save the center part of the retina. What the heck is this? Load for these vulnerable vessels. There's kind of an edge where there's a fence called the CFET. So it's called the CFET. So what do you see this in? What entities? All right, so right now if they'd be maturity, you could see this in a non-perfused area where it's just dark, of course, and getting in and then this CFET neovascularization. Again, this happens to be a patient with sickle cell. So when you have sickle cell, you get a lot of sickling of those RBCs. You get ischemia, they block it off, and then you wipe out the peripheral retina and you get the CFET. So this is a patient with sickle cell. And this is a trypsin digest showing this lumpy, bumpy, knobby vasculature from chronic damage from sickle cell. So we don't see a lot of sickle cell in Utah. We just don't have a lot of African-American patients. We saw a ton of this in Chicago, but it just depends. But you always want to keep this in mind, especially when you've got an African-American patient with some funny peripheral vascular changes. You really want to take a good history and make sure that they don't have sickle cell. All right, what do we see in right here? Exactly, so that's a macular hole. And this is the picture. What the heck is that thing in there, coming out of the hole? Exactly, sorry, I put that in once in a while to see if you guys actually look at these pictures. So if the patient has trouble fixating, they sometimes put a rod in there. So that's a fixation rod showing you that. But there's a nice close-up of a full-thickness macular hole. Of course, this is what kind of a scan? OCT. OCT, and you can see not only is there a full-thickness hole, but what else can happen with these macular holes? Ultimately, the ventroregal tractions will get attached to them. Okay, well, that's what can ultimately happen, but that's not on this picture. What else is this picture showing? It's a edema as well. Edema, exactly. So there's a little bit of edema next to this. So oftentimes you'll have a full-thickness hole, but you'll have a rim of some thickening of the cornea due to edema. So the idea now, especially with these really high-resolution OCTs we have nowadays, we want to pick these up where there's traction early on before it forms a full-thickness hole. And so we will often try to catch these early where we treat them before it causes that. And then, pathologically, you can see that here's a full-thickness hole, it's in the center of the macular, the ganglion cell there, multiple cell there, it's thick. Look at the edema now, it looks just like the OCT. Edema next to the full-thickness hole is macular. All right, what do we see in here? So, a little bit more, it looks like the OCT. And what's the hint that tells you it might be an ERM? These vessels, it's like someone has kind of grabbed them and pulled them in a little bit. And so that's the subtle sign of an epiretinal membrane. Now this is not so subtle. Again, in turn, pick this up. You can see a severe epiretinal membrane with wrinkles. And so epiretinal membrane, think of it as a cellophane membrane on the surface of the macula. And then think of it as crinkling up like cellophane does and it can cause that kind of a change. And red-free photos show this nicely. This is a red-free photo. See the straightening of the vessels? And you can see this epiretinal membrane right here on the surface of the retina. This kind of shows you, again, the OCT shows it nicely, all OCT after it. You can see, again, the membrane on the surface of the macula. And this is what it looks like pathologically. You basically get this corrugated appearance. This irregular wrinkling. And so what happens is astrocytes, which live inside the retina, you don't think of them, but there are some in there, they will gain access to the surface of the retina and then they'll start proliferating and making this epiretinal membrane. All right, what are we seeing right here? All right, what are drusen? Exactly. So we look at a drusen. Some people even call it intra-RPE. So this is a good place to talk a little bit about Brooks membrane. Now, normally, I would talk about this when I choose the normal anatomy and just this morning I forgot. So what are the layers of Brooks membrane? It's a five-layered sandwich. Good, so it's a five-layer sandwich, Brooks membrane. And so you think about it, it's like those turkey sandwiches you get at a bad restaurant where you have bread, which is the basement membrane on both sides, and you have two layers of really fibrous, collagenous turkey, and then a layer of elastic tissue, which is the cheese. So you've got cheese, two layers of collagenous turkey, two layers of bread. So it's a five-layered sandwich. So technically, if you talk about drusen, they are under the basement membrane of the RPE, but on top of the collagenous layer. So technically, they're intra-RPE. So here they are. And you alluded, Ali alluded to the fact that these are kind of waste products of the RPE building up. So if you think about it, the RPE is a very, very busy layer. What does the RPE do? What are some of its functions? Okay, how does it do that? Okay, so now Brooks membrane does not stop transfer of stuff. And so the coreo-capillaris is very porous. Materials come out of the coreo-capillaris. The outer retinal junctions that are kind of the outer blood retinal barrier is actually the RPE. So the RPE has tight junctions in it. So fluid doesn't just flow passively. It flows actively. And so you get transformation of nutrients coming from the coreo-capillaris into the outer retina, which is extremely metabolically active. What else does the RPE do? I don't know. I just said that. I just said that, yeah, absorbs. All right, so it will actually, it's got pigment in it, so it absorbs light. And so it helps to decrease glare. So if you have an albino patient, man, light really bothers them. But normally the rest of us, we've got that RPE that absorbs some of the light so we don't get so much glare. What else is the RPE? All right, so it's kind of like a recycling factory, if you think of it. So those outer segments of the rods and cones, they eventually slough off. The RPE takes them. It re-esterifies them. It makes them like new. And then it puts them back out into the retina. So it really has a, you know, a really rebuilds. It has a recycling. So if you could imagine over the years that just a lot of that stuff builds up in there. You get a lot of lipofusins and pigment, a lot of breakdown products. And eventually it overwhelms that cell. It starts spitting them out and forms these drusen, which are the first sign of age-related macular degeneration. What is this? It's a giant drusen. And so you can get small, so-called hard drusen. You can get large, so-called soft drusen. So sometimes these drusen can be really big and it causes disruption of the overlying RPE layer. And eventually you can get, you know, the loss of the photoreceptors there. And then you get the loss of vision from macular degeneration. Here you can see a lot of drusen and you can see the RPE changes starting from macular degeneration. Now, these are what we call confluent drusen. It's your drusen all along here. So you get a lot of soft drusen kind of linked together and you get loss of RPE overlying them in significant loss of central vision. So what's happening right here? This is a fondest photo of the up-to-high. What else do you see? It's kind of subtle in this picture. You see kind of drusen throughout. But believe it or not, right here, I'll outline that the RPE in this area has been completely wiped out. It's a little bit of pigment on the edges. This is what we call geographic atrophy. So when you get significant enough changes from majorly macular degeneration, the RPE gets completely wiped out and you get what's called geographic atrophy. So this is what it looks like. Here's Brooke's membrane right here. You look right here, the RPE has been completely wiped out and therefore the retina overlying it has got no, you know, none of the RPE functions taking care of it so it gets wiped out. So this is what's called the end stage of geographic atrophy. And so this is macular degeneration. Unfortunately, we don't have good treatments for this yet. What do we see in right here? Oh, I'm sorry, question. Yes. We're like pseudo-drusen or reticular drusen that are above the RPE. Do they, does that not interfere with its function and transport everything? It does also. Yep. So they're kind of like, think of reticular pseudo-drusen as they kind of like do the same kind of damage that drusen do. All right, well, we're there. What is this? Yeah, so you can see, blowing the inferior back, maybe a little hemorrhage there, it looks elevated, I want to go to the front of the reflex. And then you can see like a darker, deeper, greenish-grayish color, which makes me think that there's sub-retinal fluid there. Yeah, so when you see this dark greenish color, not only is it sub-retinal, but it's actually sub-RPE. So this is a sign of neovascularization. It can be under the, you know, under the retinobit can also be under the RPE. And when it's green like this, the RPE is still overlying. And so this is neovascularization from age-related macular degeneration. And this is a nice picture. I had to copy this because I didn't have a pretty picture like this, but here's the coroid. Here's the overlying retina. Here's some fibrosis going on here, gliosis. And here's a break in Brooks membrane and you see the neovascularization coming through, going underneath the RPE. So you not only get hemorrhage, but you also get fibrosis from the wet macular degeneration. This is a severe one. This is sub-retinal when it's red and kind of sub-RPE when it's green or black. So this is a severe neovascular membrane underneath the bacula. You can see right here, here's an area of a focal neovascularization with fibrosis. So you'll start to get fibrosis underlying this. Here's a close-up. Sub-retinal fibrosis, RPE broken up and a few little tiny vessels right in here. So neovascular, fibrodech membrane underlying the macular for mutilated macular degeneration. This is a severe one. We used to call this a disciform scar which is a dense, thick, fibrodech scar underlying the retina. This is the end stage of neovascular age-related macular degeneration. All right, what are we looking at right here? So there's a fundus nodus, scarring, focal spots around the macular, as well as around the retina itself, kind of consists of potentially some disciform scars, but it's still fine. So some scarring in the retina, but what are these lesions? They're away from the retina and they're round and fairly distinct. This is a tip-off for something else that can cause neovascularization of the macular. Not disciform scarring. Well, it can cause disciform scarring, but in age-related macular degeneration, you don't have these peripheral lesions. What entity can you have peripheral lesions along with the macular lesion? Isn't that the case of plasmusis? Exactly, so now you have to put the P in front of it. The P stands for presumed ocular histoplasmosis because we often don't find living bugs in there, but you can find evidence of previous histoplasmosis infection and these are called the punched-out lesions. And so they call them punched-out because they're focal and they're like punched-out lesions in the periphery and then eventually you can get some neovascularization and some scarring in the macular. So this is presumed ocular histoplasmosis. What are we seeing right here? Yeah, you kind of see some elevation here and so you would be really suspicious that something's going on in here. And so we do a fluorescing angiogram. Remember what those were? Do you guys still do fluorescing angiograms? I know we had the, we call the Foursing Angiogram Conference, it's mostly OCDs, but you can do a Foursing Angiogram and you have this picture. What is this show? It shows a lot of things in the statement practice. All right, so if you remember, we showed you Henley's layer that goes out leakly. So when you get leakage in the area around the phobia, that fluid tends to track along Henley's layer and they call this kind of a flower petal distribution. So this is cystoid macular edema. And this shows it pathologically. Remember we said it's in Henley's layer or in the outer plexiform layer right here and here you see exudate here and here. Here's the outer nuclear layer, inner nuclear layer, and it's right there in Henley's layer. There's the ganglion cell layer, multiple cell layers thick. So this is cystoid macular edema. All right, what do we see in here? So this is what, yeah, gosh, I don't know if we can turn those lights down a little bit. My view is so much better than this. I'm sorry, we've got, I don't know, that helps a little bit. This is one where you kind of have to use your imagination and looking at this pattern. So I apologize, this shows up much better on my picture than up there. This is a bullseye maculopathy. So if you look, you can see some modeling of RPE here and then a more red outline around it. So this is called the bullseye maculopathy. Now, what are some entities that can cause bullseye maculopathy? Sometimes some of the psychiatric meds can cause this too, but most common one that you may be seeing patients in clinic to rule out is plaquanil toxicity. And so you obviously don't wanna let it get to this point. You wanna recognize it sooner. And nowadays, we can do macular OCT, we can do central visual fields and patients who've been on plaquanil to make sure they don't get to this point where you get this bullseye maculopathy. This is the fluorescein angiogram. And rather than leakage, you get a little tiny foaming staining of that area. And this shows the bullseye pattern much nicer when you do the fluorescein. So bullseye maculopathy. What do we see in right here? This looks like angioid streaks. Oh, all right. So again, almost kind of like deeper medusa snake heads. And so these are what we call angioid streaks right here. What are angioid streaks? Brakes and brooks member. Exactly. So their focal breaks in brooks member. Now, why would I be showing you a picture of somebody's neck? I'd actually just love to do this. You know, they have no monolastic. Exactly. So they call this a pluck chicken look. I mean, I'm not from the farm like some of you Iowa people are. I don't know what a pluck chicken looks like, but they call this the pluck chicken look. And so you can see the skin, this is a patient with pseudosanthoma elastocone. And it's a connective tissue disorder and therefore it affects brooks membrane. So you can get these angioid streaks and they can sometimes allow neovascularization to form. So they're important that you recognize those. What are we looking at right here? Exactly. So this picture kind of shows you pretty much all the findings of an advanced retinitis pigmentosa because you get wiping out of the retina, you get a pale optic nerve, you get the vessels markedly attenuated. And then as you go out to the periphery, they call this the bony spigula pigment. And so what happens is the RPE gets disrupted and then the pigment will track along the blood vessels. That's why you get that bony spigula. The pigment is released from the damaged RPE and then it'll almost diffuse out along the blood vessels. And there's the blood vessels there with the pigment on it. And so that's what you get in retinitis pigmentosa. And again, the retina guys will talk to you about the various genetics and all the other factors involved. But pathologically, the final common denominator is that the retinopigment of the feeling gets wiped out, the retina itself gets atrophied and then you get the pigment along the blood vessels forming the bony spigulas. What do we see in right here? This is the yellowish elevation of the Bermuda cycle. Yeah, so it kind of looks like, we like to tell people it looks like an egg yolk. So if a teleformed dystrophy or there's a type of a teleformed dystrophy, best dystrophy that can look like this. So you see that egg yolk underneath the retina in the center. And you can see this fateliform lesion is actually underneath the RPE right here forming the yellow form maculopathy lesion. Okay, what do we see in right here? So people call these pieceiform, pieceiform literally means fish-like. And so if you think about Nelso goldfish, you know, crackers that you eat, it kind of looks like, kind of, again. You know, people sometimes you wonder how they describe these bits called pieceiform. So you see these little tiny changes here. And so this is consistent with, you said it, Stargardt's disease, okay? Or fundus flavium aculata. And so this is characterized by deposition of lipofucin into the RPE right here. So it's lipofucin rich and can disturb the macula also, but then can cause these peripheral lesions, Stargardt's disease. What do we see in right here? We really see very many vestibules. So I'm gonna see if there's any vitritus. Exactly, so this is a vitritus. And people call this, look, the headlight in the fog, the headlight being, all you can see is a little bit of that white optic nerve head through the fog. This is vitritus. So what are some of the things you think about in vitritus, okay? So when you think about it, when you see this kind of vitritus picture, you wanna make classification. So I tell people, make little mailboxes in your brain like the mailboxes upstairs. So one mailbox says inflammatory, one mailbox says infectious. There's a third mailbox you wanna always keep in mind when you see a vitritus. Exactly, so you've got what your retinal lymphoma can present as a vitritus. And so those are kind of the three categories you always wanna keep in mind when you see a picture like this. And this shows you kind of the path on this. This was that, maybe had that picture five years ago. So what do we see in here? What do we think the diagnosis is here? This was toxa. And so when you have toxa acutely, you get the headlight and the fog, you get a vitro retinal inflammation. And then eventually when it settles down, you get this heavy pigmentation with these white lacunae where the RPE's been totally wiped out in this area. And so this is a previous toxoplasmosis that's not actively infected. When you look at it pathologically, you can see the RPE gets totally wiped out in this area. I think we can go up on the end. This is an ocular toxoplasmosis. All right, what do we see in here? So when you see a patient like this, they call this again maybe the ketchup or the pizza look to it. And so this could be CMV. And then we look and when you look at the retina itself, you can get intra-retinal, I mean intra-nuclear and intracytoplasmic inclusions. So you get these swollen retina cells. And so this can occur in people who are immunocompromised. We used to see it in people with HIV before we had triple therapy. But even people who have undergone bone marrow transplants or are being treated for a systemic cancers can get CMV retinitis flaring up. All right, so we say goodbye. We've made it. We say goodbye to the glomo and melano. Next time I believe it's orbit. I don't know, but please look and see. So please read that section of the BCS ahead of time. And we'll go ahead and do that. And then we're just gonna, you guys have me for the next seven Tuesday mornings at seven a.m. Oh, we've got exactly two minutes. Questions? Was it the future of toxoplasmoplasmosis? Was that the funnest photo of the rest? You know, I can't put anything by you guys. This is a nucleated globe that was doing it. So that's why it looks that way. So this is actually a globe that's been cut. That's what allowed us to have that path picture. Yeah, a good pickup. How's a good pickup there? So you get the gold star for the day. That was a good pickup. All right, any other questions?