 All right, so we're going back to Paris again. And this is the Musee d'Orsay, where they took an old train station and made it into a museum. This has all the impressionists in it. So it's, you know, if you like impressionism, this is the place to go. And this is the insides. You see, it's still got the characteristics of an old train station. They've got the glass atrium here. And then all the galleries are on both sides, both up and down. I mean, it's pretty amazing when you just see, you know, 1,000 impressionist paintings. So, and they've, you know, like everything else in France, it's very ornate. This is the ceiling looking back up, extremely ornate. Chandeliers, I mean, not your average train station. So very, very beautiful place. And of course, it's got the murals on the ceiling. So even if you're not looking at the art, you're looking at the building that's housing the art. So it's a pretty cool place. All right, so we're going to talk about the retina today. And again, saying that we said last week, would ogres, onions, and retinas have in common? Layers, OK, layers. So first of all, we just want to look at a picture of a retina. And so we're going ahead and looking at the picture. I want you guys to realize that there are a couple of definitions that you need to know. And so when you're looking at a retina, in terms of the macula, the retina guys define the macula as the area within the arcades. Chris, how do pathologists define the macula? Is the area within the arcades? Well, more than one layer. More than one layer of ganglion cells, exactly. But it pretty much corresponds anyway. I mean, it pretty much is the area within the arcades right here. So that's what we're talking about. All right, so we're talking about layers. And so we're going to start at the vitreous end, and then we're going to go through to the sclerulent. All right, so Brad, here's the vitreous. What's the first layer right here? All right, what's that stand for? All right, so the internal limiting membrane, all right? Sneha, next layer, neurofiber layer. We'll just go across, Rachel. Ganglion cell there. OK, Allie, your plexiform layer, very good. Sorry, guys. You are, I'm Jordan, a third-year med student. Oh, Jordan, OK, we don't pip students. So you're saved for today. All right, back to Chris. Outer nuclear layer. Outer nuclear layer. These, right. Photoreceptor layer. Photoreceptor layer. Book's my brain. Yep, that's good. Allie, it's more specifically part of the coroid, but burial capillaris, exactly. So it's just the innermost part of the coroid. Let me say that that's the point. You see multiple little tiny capillary channels. This is where a lot of the exchange of nutrients and removal of waste takes place. All right, so we're looking at it a little bit higher power. Now, let's think of it functionally in terms of what's in each layer and what part of it is there. In order to do that, you have to kind of think of the retina as you want to think of it as what happens to a photon of light. So a photon of light comes through. It's refracted by the cornea, refracted by the lens. Eventually hits the retina. Now, it's interesting in that the retina is upside down. Photoreceptors aren't on the inside sticking up, looking where that light's coming through, because they have to be extremely close to the nutrients because it's a really nutrient-rich environment. And so a photon of light comes all the way down here, and it hits some of these little outer segments of the rods and cones. So what happens at that point? Exist a transfer gobs in here. So you get a transistor retinol. You get a hyperpolarization of that membrane. And then it goes through from the outer segments to the inner segments to the cell body here, which lives in the outer nuclear layer. All right, Chris, where does it go from there? Where does that signal? It goes to the inner nuclear layer after that. Where does it synapse? Bipolar cell. But where does the synapse first? Where does the synapse actually take place? Synapse from the rod and cone cell axons to the bipolar cells. It takes place, what's this layer here? Outer plexiform layer. So that's where the synapse takes place. And then that signal goes up to a bipolar cell. So it's right here. Then it comes out of the bipolar cell. And then where does it synapse again? The ganglion cell layer. The ganglion cell. Well, it synapses here first before it gets to the ganglion cell layer. Then it gets to the ganglion cell. And then where does that axon go when it leaves the ganglion cells? Now? To the nerve fiber layer. Nerve fiber layer. Now, where does that axon synapse? The lateral. Exactly. So that axon that lives right here, it goes all the way through the nerve fiber layer. It goes through the optic nerve. It goes through the chiasm, through the radiation, all the way back to the lateral genicular body before it synapses. So that's a really long axon. Anything that interrupts it along that way can cause degeneration eventually of those ganglion cells. All right, now, what part of the retina are we looking at right now, Rachel? Exactly. So you look at the ganglion cell layer here. It's more than one cell layer thick, so you know you're in the macula. There's one other area that's really unique to the macula. Alley, we're looking at these fibers out here in the outer plexiform layer. What's going on with those fibers there? They're going oblique. So what do we call that particular layer? Henley's layer, exactly. So again, we got to train you guys when you do oral voice. Say it with conviction. Henley's layer, Henley's layer. If you let your voice come up, you're guessing. So Henley's layer. So what happens is, if you think about it, in the center of the fovea, that's the point of where we get our maximum vision, and our fine vision, and our detail vision. And so that is stuffed full of cones. Because you want to see every little detail, a single cone goes to a single bipolar cell, goes to a single ganglion cell. And so all those cones are stacked up, and they're trying to get to all those ganglion cells, which are stacked up here, so as a result, some of these fibers are unobliquely. So this cone over here may link up with the ganglion cell clear over here. And so that's what's called Henley's layer, where they run oblique. The reason that that's important is that layer is where sisterhood macular edema occurs. When you get sisterhood macular edema, it's out in Henley's layer. And then again, all these ganglion cell layers are stacked up because they have to take cones that are coming through here. Now if you go to the peripheral retina, peripheral retina is really to help you see your peripheral vision, help you see movement, help you see things going on out here. And so in the peripheral retina, you might have 100 rods funneling into a single ganglion cell. And so the result of that is it summates. I don't know if you've ever been there. You're out. It's like a night, and you see a little light out of the corner of your vision, then you look at it, and it disappears. Because you just, it summates it, so you can see it. And that's important teleologically. You want to see movement. You want to see light. You're out on the tundra. You don't want to have that sabertip tiger grab you and kill you. So you want to be able to see that movement out of the corner of your eye. So in the periphery, again, 100 rods may go into a single ganglion cell. But in the macula, one cone, one bipolar, one ganglion cell. Now there's some other cells that live in this really, really busy layer or near this inner nuclear layer. What are some other cells that live there besides the bipolar cells? Amicron? Amicron cell, OK? Another one. Horizontal cells. Horizontal cell, and one more. Neular cells. And so if you think of the horizontal and the amicron cells, they run aero. They don't run perpendicular. And their purpose is they actually begin to summit and process sight in an early phase. And so you don't actually have a signal go straight through the brain to the lateral genicular body and then the brain. There's processing going on even in the retina. So those amicron cells and those horizontal cells will touch multiple other processes. And they are starting to summit and process visual images right at that point. And then the Mueller cell is almost like a microglial cell. And so it sends its little fibers all the way up almost to the internal membrane and all the way down here. Now, some people call this the external limiting membrane. It's not really a membrane. It's the little junction between the cell bodies right here in the outer nuclear layer before you get the actual cone and rod bodies right there. So very, very busy, busy, busy layer there. So here we have the fovea. This is the center part of the macula. And I think the fovea is like wind parting a wheat field. And so you look at it. You see that it thins out here. And then all you've got is these cone bodies right here. And then the actual cone is here. And so again, Henley's layer runs this way. So these cones right here may link up for those ganglion cells clear out here. That just shows you again Henley's layer and how that's happening. All right. So we're going to start looking at some diseases that affect the retina. Brad, what are we seeing here? So we have a funnest photo of the right eye. We have kind of just almost all four quadrants with flame-shaped hemorrhages. And then it looks like in the macula area we have some exudate as well. So it looks like this is the hypertensive retinopathy. OK. Now what else could this be? It could be diabetic retinopathy. Exactly. So sometimes diabetic retinopathy. If you look at where the hemorrhages are, these superficial hemorrhages are shaped like flames. Why is that? Because they are. Exactly. So remember, the nerve fiber layer turns and then runs parallel to the surface. And so if there's hemorrhages there to look like flames, if there's hemorrhages down deeper, they'll look like little dots and blots. And so again, this could be hypertensive retinopathy. But diabetic retinopathy looks like a lot of other things, too. So this technically could be diabetic retinopathy. And it turns out that that was indeed hypertensive retinopathy. Now there are some other things that you can see with hypertensive retinopathy. Sneha, what else can you see beside the hemorrhages and the exudates? Exactly. So if you look right here, look at that optic disc. It's kind of hazy. And so that's a little bit elevated. You can get a swollen disc here. You've got the flame hemorrhages here. Interestingly enough, look at the exudate and the macula. It takes the pattern of a star. And so once again, that corresponds to Henley's layer. So you get this star shape exudate. This actually took this picture of myself. Sadly, this is a nine-year-old kid and came in with headaches. And we had to look in her eyes and did how to know my god, measured her blood pressure, 200 over 100. Turned out she'd had ureteral reflux for years. Nobody knew. And she actually had severe kidney disease and so severe hypertension. So this is what severe hypertension can look like. You can even get papillodema, in addition to the hemorrhages and the macular exudates. And this is really severe. So this was a patient, again, who came in from the ER and came in complaining of headaches. And you can see these people, I mean, not all the time, but not infrequently. You'll get referred from the pressure of 220 over 110. This is what they can look like. Severe disc swelling, loss of the margin, hemorrhage is there, cotton wool spots, ischemia. And so this is severe hypertensive retinopathy. Now, this is a little bit different here. Rachel, what does this look like? What do we call that? Cherry red spot. Why does that occur? You still have some corticopolitis blood flow that you can kind of see through underneath the phobia just because it's thinner than it is now. Exactly, so this is like a window. And so in the center part of the phobia, remember, all those superficial retinofibers have parted it. And so you don't have that ischemic retinoverlying. And so you're looking at normal coreoidal blood flow still, right there, so that's the cherry red spot. So you see a ischemic retin. And the common cause of that is? Serial. Serial, central retinal artery occlusion. What are we seeing right here, Allie? It looks like a more focal area with lightning, the wall spot, the BRAO, ranch. Ranch retinal artery occlusion, exactly. So are most artery occlusions embolic or thrombolec? Embolec, so usually there's an emboli from somewhere. Carotid, aorta, valve, somewhere, a piece of cholesterol, a blood clot, something is getting in there, it's blocking them. And so when you get it right at the optic nerve head here, you'll get a central retinal artery occlusion. When it goes down further to a branch down here, then you get a branch retinal artery occlusion. So this is a branch retinal artery. What am I showing right here? Hang on. Heck is this. Why would I show you this? Yeah, we're looking surrounding it is nerve tissue. So we're looking at central retinal artery. So this is a central retinal artery coming out of the optic nerve. And this is a person from Utah who loves to go to Crown Burgers and Mucci's and all those other places that I like to take you guys to once a year, and you know, that lovely high fat diet that we all eat. And so this is severe arteriosclerosis. So it's rare that you'll have a central artery occlusion and a normal artery. I mean, I guess, yeah, you could have a giant chunk of cholesterol break off your neck. But usually what happens is the artery will be narrowed and will be hardened and will be thickened with arteriosclerosis. And then you'll have this narrowed lumen, and then it can block off easier. What is this thing right here, Mike? It's like the vein. So the most common cause of central retinal artery occlusion, I mean, is arteriosclerosis. What's the most common cause of central retinal vein occlusion? Also arteriosclerosis. And so if you think about it, the vein and the artery come through together in the optic nerve when they're coming into the center of the optic nerve head. And so as a result, when you have that big sclerotic artery pressing on the vein next to it, you can actually get stasis, which then leads to a central retinal vein occlusion. So arteriosclerosis is also the most common cause of central retinal vein occlusion, because they come in together into the optic nerve sheath. And this shows you what happens when you have a central retinal artery occlusion. And this kind of illustrates the blood flow to the retina. And Chris, what is the blood flow to the retina? The central retinal artery. Actually, flip that. Exactly. Yeah. So the central retinal artery gives you the inner two thirds. The cori gives you the outer third. So if you look right here, this is patient at central retinal artery. The ganglion cell layer, nerve fiber layer, outer nuclear layer, I mean, inner nuclear layer, and about two thirds of the outer nuclear layer have been wiped out. So that's central retinal artery. Whereas the outer nuclear layer and just a little bit of the inner nuclear layer and the rods and cones get their blood from the coroids. So those are still alive. And so that's carotid blood supply still going up. But it doesn't matter because you've wiped out the retina. So that signal is not transmitted. So the inner two thirds of the retina gets its blood supply from the central retinal artery, the outer third from the cori. And what do we see in right here? Yeah, so it's a pretty obscure view of the entire retina. And so I would, one of the things in my differential would be a CRVO. So this is what they call the blood and thunder retina. I don't know what thunder means, but blood and thunder. So it sounds like a defense, like, ah, the Chicago Bears, blood and thunder defense. So this is where you've got a central retinal vein occlusion, and you get back up all the way through. 360 degrees back up all the way through. So very, very backed up, very dominant. So you have a wreck on the freeway. All the cars get stacked up. What is the difference? Here's now. All right, exactly. So this is a branch vein occlusion. And where does the occlusion occur in a branch vein occlusion? What specific point is susceptible for that to happen? Exactly. So if you look at this, look at this arterial, they used to call this silver wiring. And so you can actually see arterial sclerosis within the arterial here. And it's where the vein comes off and crosses over where that thick artery is. And again, it'll pinch off that vein, and then that vein will block off. So again, arterial sclerosis is the cause of vein occlusion, even in a branch vein. So this, you just have a blockage in one focal area. So this is a branch vein occlusion. This just shows you in a central artery occlusion that goes all the way to the aurisurata. So this is a globe that's cut in half sagittally, optic nerve back here, aurisurata up here. You see hemorrhage diffusely all the way through that globe, central retinal vein occlusion. And when you look at the path, you'll get ischemia with that. You'll get blood backed up with that. And again, it really disrupts the retina. So you can see all the way from the rods and cones to the inner part of the retina. Blood all over, exudate here. It really disrupts the retina. So you get ischemia, you can get on other problems as the blood just doesn't get out of there. And what are we seeing right here, Allie? All right, this is diabetic retinopathy. What is this right here? Very subtle, but there it is. Little cotton wool spot. And so this well, well, pretend that's not there. This would be what we call background retinopathy. But there is, this is getting more into a little bit of even pre-perliferate retinopathy. But this kind of illustrates the different changes in the background retinopathy. So the first thing that happens is for some reason, the perisites get affected that surround the little arterials. And then what you do is you get these little micro aneurysms forming. So this is a trypsin digest of the blood supply in the retin itself. And you see these little micro aneurysms. So that's the first thing that you see in background diabetic retinopathy is the micro aneurysms. And then you can get the hemorrhages, dot blot, flame hemorrhages. What is all this stuff right here, Mariana? All right, makes it is. All right, so you can also get a tremendous amount of heart exudation. If it's here in the macula, you can imagine that that's gonna cause a lot of issues with the vision. So it's a sign of diffuse leakiness of the vessels. And so you get leakage of all this fluid through there. Eventually some of the fluid gets reabsorbed with the lipids, the proteins, other stuff like that does not get reabsorbed. So it ends up depositing in the retina. So the heart exudate gets deposited in the retina. And this is what it looks like. Here's the retina and cross section again. This is an influx staining material. This is heart exudate. I don't know why they call it heart because they used to call cotton wool spots soft exudates. It's not an exudate, but in any event, it's a heart exudate. So that's what it looks like right there. All right, now, what do we see in here? It looks like I got a bunch of photo, left eye, and you got those cotton wool spots. Cotton wool spots. So if you look at them, they're different. They're not that yellow heart exudate inside the retina. It's almost like it's descriptive. It's like someone took a little fluffy piece of cotton and put it on the surface of the retina. Why is that? And what causes it? The infarct in the area. Exactly, so it's an ischemic infarct. And so when you look at it right here, what a cotton wool spot is, is it's swollen ganglion cells and nerve fiber layer. So it looks as if it's on the surface of the retina. And when you get that acute blockage, that acute infarct, then it swells. Now, those can go away. They can wax and wane, but unfortunately, permanent damage in that spot. It's tough to pick up. And sometimes if you do a multifocal ERG, really specifically, you can pick up some little areas of damage. And so a cotton wool spot is a focal area of ischemia of the inner retina. Now, you're seeing close up, these are these swollen, sorry, I copied this out of a book. I didn't get a beautiful slide like this. This is swollen ganglion cells here and nerve fiber layer. So that's an ischemic swollen cotton wool spot. What are we seeing right here? Chris? We're seeing, looks like proliferative retina. So we're seeing areas of neovascularization. It looks like PVF kind of a spot. So what do we call this now? This would be part of it. And so we divide it into NVD and NVE. So neovascularization of the disc and neovascularization elsewhere. So this is NVE, neovascularization elsewhere. So you get chronic ischemia. Ischemic factors are produced. They cause abnormal blood vessels to grow. And so you get this neovascularization elsewhere. But also you can get this. Brad, what is this? NVD. NVD, neovascularization of the disc. And we call this the medusas. And remember Medusa from Greek mythology? The lady had all the snakes coming out of her head. So this looks like Medusa right here. You've got all this neovascularization right here. And so this is NVD. Why is that an issue? Exactly, it can bleed, it can cause scarring, it can cause all kinds of problems. Because those abnormal vessels are not mature. They don't have perisites around them. They leak like crazy. And in fact, you can get this. And so you get hemorrhage, you get gliosis, you get traction, you can get a retinal detachment because of this, a traction retinal detachment. And you can even get this. Now what kind of hemorrhage is this called? Boat shape. You see it's flat on top, round on the bottom. Why is that? Exactly, so this is actually pre-retinal. So it's in front of the retina, between the retina and the vitreous. And so the blood will leak down over there. Then it'll have this flat top on top. So this is NVD causing pre-retinal hemorrhage. And so it can cause severe hemorrhage if you don't treat that. What else does this cause, Rachel? Neovascularization of the iris. So we call this rubeosis irritus. And we used to call this ropeosis, because it looks like big ropes all over. So when you get chronic ischemia, not only does it stimulate abnormal blood vessels to grow inside the retina, but it stimulates abnormal blood vessels to grow on the iris. And so you can get severe neovascularization of the iris. And just remember from last week, you can also get neovascular glaucoma. So here's the blood vessels on the surface of the iris. That membrane is pulling the pigment epithelium around the corner. So when you look, you'll actually have a little black border. What do we call that to the iris? Ectropion UVA, exactly. So it pulls the black border iris anteriorly. So that's from neovascularization. And there you can see where the neovascularization is actually closed the angle. So just like we talked about last week, secondary angle closure glaucoma. Now, diabetes can cause other things going on inside the eye, beside just the retina. What the heck is this picture, Allie? What's going on here? I'm showing a picture of the iris and it looks like there's like, vaculization of it. Exactly, so you can get this focal vaculization of the iris pigment epithelium. They call this lacy vaculization. And that's a sign of diabetes. Arianna, what am I looking at right here? This is pars placata neovascularization, I think, in those red areas. Look closer. What kind of stain is this? So what is PAS stain? Basement membrane. Basement membrane. So what happens in diabetes in the silver body? Exactly, it becomes thickened. So you see this is the basement membrane of the silver body epithelium. Look how thick that is. And so when I was a fellow, I hadn't done my residency yet. So David Appel was too busy doing the IOLs. He didn't want it to pass. So the American board of ophthalmology said, hey, can you send us some good path pictures we can put on boards? And so he said, Nick, you don't get it. So I took a bunch of good pictures and so I actually took a picture just like this and submitted it to the board. And so when I was a senior resident, my picture was on LCAPs. And so I looked at it and I said, we can basement membrane diabetes. I got this cold. And then, as you guys, if you haven't taken these LCAPs yet, you'll love them because LCAPs ask two-part questions. So you look at this, you say, I've got this. This is a diabetic. And then they'll say, a patient with this picture would have, A, perineal nerve velocity of, B, creatinine clearance of, and then you're like, oh, shoot. What is a slow perineal nerve? What is decreased clearance? And so they asked two-part questions. So it's really not fair. You get it right and then you still don't get it right. So you guys, there are more seniors you'll love taking this. It's great. So this was funny because this picture actually showed up on the boards on the LCAPs when I was a senior. So the good basement membrane of the ciliary body. All right, how do we treat this? Nick, is this? This looks like laser treatment. All right, so it's interesting. When people first started getting lasers, the first ophthalmic laser in the 1960s was a xenon arc laser. This thing would blast a thousand micron thing that would like melt lead. I mean, it was this really, really, really bright spot. And interestingly, when they first started trying to treat neobesquerization of the iris, they would treat the neo itself. The theory being that the laser would actually, you know, seal off the neobesquerization. So they blasted the optic nerve head with this laser. Well, of course, people went blind from that. But people were also using the xenon arc in the periphery, blasting neobesquerization in the periphery. And what they found was after that, the neobesquerization on the disc went away. So then they finally figured out, wait a minute, this isn't sealing off the abnormal blood vessels. This is actually treating ischemic retina, which then decreases the ischemic factors, which then causes the neobesquerization to recede. So, you know, right now, of course, we've got the injections that people are using. So we're seeing less laser treatment. But the idea was you would treat the entire peripheral retina to save the central retina. And so you would sacrifice that peripheral retina. But then the neobesquerization on the disc and the macula and all would shrink up and you'd save your central vision. So this is what the laser spots would look like. When you look at it pathologically, you know, when you look now, we use an argon laser. It basically works by being absorbed by pigment. And so here's the normal retina over here. Here's RPE outer retina. Here's where a laser spot is. You see it basically wipes out the RPE and a lot of the external retina. It kind of seals off the cord of capillaries as a result of that. It will decrease the factors that are being put out that cause the blood vessels to grow. Some people also say it might increase oxygenation into the retina from the cori too. But any event that does work when you do peripheral pan-retinal laser photocoagulation for neobesquerization. All right. What? Let's see, did you do that last one? It does work. Chris, what is this? So here we're seeing this as an FA. And here we're seeing this kind of peripheral kind of C-fan appearance. There's capillary non-perfusion and drop-drop discolidant. So we can see stuff like this in sickle cell. You can see this in uterus disease. Kind of be a couple that come to mind right away. Good. So this is, you look at it, that it's dark in the periphery because that retina is totally ischemic. And then right at the border zone between the ischemic retina and the perfuser retina, you get this C-fan neobesquerization. This indeed was a patient with sickle cell. And so we don't see sickle cell much in Utah because we don't have a lot of African-Americans in Utah. But in Chicago, we used to see tons of sickle cell. And basically what happens is, you know, when these RPC sickle, it causes capillary blockage and then causes chronic ischemia. This is actually this knobby appearance you get in the retina. Again, in trypsin digest, this knobby appearance that you get in people with sickle cell. There's a really rare condition called deals disease again that can do that. You know, nowadays it's interesting when you're looking at people treating retinopathy and prematurity with injections, you're sometimes now getting these little C-fans in the area between perfused retina and non-perfused retina and premature infants. And so same idea. All right, this is kind of subtle, the heck is. So it looks like we have an macular hole with maybe a little bit of surrounding sub-retinal fluid. Exactly, so that looks like pretty much a full-thickness macular hole. And then you do see that little cuff of fluid surrounding it. And here's a close-up, what is that thing? It's a fixation rod. Exactly, so sometimes people look at it and say, I don't know, it's that focal. Here you have extra data. So that's actually the fixation rod. Sometimes these people can't hold the eye still so you give them a rod to look at. But again, you see this full-thickness macular hole and this little cuff of edema surrounding it. And I apologize, this is an old AFIP slide I took a picture of because I really, and you don't need nucleotides for macular holes. And so this is kind of the edge of a macular hole and here's the edema that you've got that little cuff of edema next to it. Boy, this is even more subtle. Sneha, what is this? So you see that little kind of sole wrinkling and you see the little accordioning of the vessels and so epiretinal membrane will give you this and so that's a little bit more prominent. So hopefully you wouldn't miss this one. This would be one maybe an intern could see, you know. Hopefully, maybe even a student, I don't know. This would be a student's one. And so you can see the wrinkling that you, let's go back. So you see the wrinkling and you can see again the corkscrewing of the vessels. That's an epiretinal membrane and as it constricts you'll get distortion and the patient will complain of metamorphopsia. Some kind of picture is this that highlights that, Rachel. It's a red-free and so if you do a red-free photograph it really tends to highlight the epiretinal membrane and you can see how the vessels, sometimes they get pulled in to the center or sometimes the peripheral vessels get elongated as they get pulled into this mass right here. Of course, nowadays we've got OCT which just shows it beautifully and so you'll see the wrinkling on the surface of the OCT as you go through the center where that epiretinal membrane is. And again, you can just see again, here's the OCT here, the wrinkling of the retina underlying it. So that's the epiretinal membrane. Now, again, I had to take a picture of this from a book because I don't get a lot of path with an epiretinal membrane on it but sure enough, here's the membrane on the surface of the retina. You know any more, the OCTs are so good compared to the path picture with the OCT anyway. What do we see in here, Allie? All right, so some drusen in the macula. What exactly are drusen? Okay, and where do they live? Well, part of the retina. Under the RPE, and this is a good place to shove this in. A PIMP question that I forgot to even mention. Oh my goodness, a PIMP question. So how many layers does Brooks' membrane have? Brooks' membrane's between the RPE and the Chorate. Five, and what are they? Or the Chorate, and then elastic, two elastic layers, and then collagen in the middle. Flip that last part. Two collagen and elastic. Two collagen and elastic. All right, so the way you remember it, it's a turkey sandwich, bread and bread, you know turkey, collagen, you know really bad turkey sandwich, really hard collagen, and then the elastic layer in the middle is a layer of cheese. And so you've got the elastic layer in the middle, two layers of collagen, then basement membrane of the RPE, basement membrane of the coriocapolaire. So technically, these drusen are actually intra-Brooks because they're really under the basement membrane of the RPE. So sometimes they make PIMP you on that. So you know it's under the RPE, and you can say, well, technically, if you want to impress the attending that's asking, you say, well, technically, it's actually intra-Brooks because it's under the basement membrane, and then they'll go, so you get extra points from it and then they'll stop pimping you, so it's good, you get points for that. So you can see this deposition, and again, it's this waste material, there's a lot of lipofucin in it, there's some lipid in it. It's kind of a buildup of waste materials, if you will, underneath the RPE. And then this is what we call a soft drusen. And so the little focal ones are what we call hard drusen, but you can get more diffuse drusen that we call soft drusen because they're even bigger and have less distinct borders, and this is what they look like. Here's the RPE over here, really disrupts thing, and of course if you can imagine, if it's disrupted the RPE, eventually the overlying retina's gonna die off and you're gonna lose vision in that area. And these are some softer drusen, just not quite so distinct soft drusen. Here you can see diffuse soft drusen, degenerative RPE cells overlying them, choreo-capillaires down here. You can see where that could cause quite a bit of disruption. Arianna, what are we seeing here? Pigment changes. What else? I know it's kind of subtle because this is a lighter, a lighter fundus. Yeah, so we call this geographic atrophy. So, you know, it's hard to see because it's a lifeless, believe it or not, the RPE is completely wiped out all through here. And then there's some pigment at the edges, and so this is what we call geographic atrophy. So, you don't get neovascularization, but you get the RPE just gets diffusely wiped out and then the retina overlying it, of course, gets wiped out. You look at the pathology here, there's brocks. Man, there's just, you know, there's some drusen here, but boy, there's just no RPE there at all. It's totally wiped out and as a result, the retina overlying it. Look how it's all vaculated. So, the retina gets completely wiped out overlying it. So, that's geographic atrophy. What are we seeing right here? Like some neovascularization there. What makes you say there's neovascularization? Central red area. So, the other thing you see, see this kind of greenish gray around here, when you get blood under the retina, especially under the RPE, it'll look kind of greenish gray rather than red. So, this is subretinal neovascularization. It can be subretinal, it can even be sub-RPE. And so, this is kind of the most advanced stage of macular degeneration. And again, I had it copy this out of a book. It's beautiful pictures. So, there you see, here's coroid. Here's brooks membrane. Here is RPE really disrupted and some gliosis here. Look, here's a brachium brooks. And here's neovascularization growing up through brooks membrane under the RPE and then forming this gliotic membrane. So, that's subretinal neovascularization. And of course, this is severe. So, this is now broken through under the retina, where it's red. And then the grayish dark one is actually sub-RPE. So, this is subretinal neovascularization. Now, most common cause of subretinal neovascularization is obviously AMD. What's another cause, Chris? That's got trauma. Trauma, you can get a focal coroidal rupture can do that? It's sub-retinal neovascularization. So, HISTO? Yep. Presumably, ocular HISTO can do that too. And so, Sneha, another thing that can cause sub-retinal neo in the macula. How about something looking around this room that's exceedingly common in this room right now? Myopia. So, myopia can cause it too. So, severe myopia. Lots of causes of sub-retinal neo, but of course, the most common one that we see is actually due to macular degeneration. And here you see, this is what we call a disciform scar. So, eventually, when you get that bleeding, you get the astrocytes proliferating, you get gliosis, and you get this scar underneath the retina. So, this will often look white. It'll look like just a big scar. All right, what do we see in right here, Rachel? Mesh spots. What do you think this could be? HISTO, since Brad just mentioned it. Yeah, so Brad did mention this, so he kind of stole your thunder here, but you see these peripheral, they call them punched out lesions. These little peripheral punched out lesions, but you can also get macular lesions with this, too. And they say, presumed ocular HISTO because it's, you don't actually go in there and biopsy it and find active HISTO in there. And so, but this is common in the HISTO belt. And it's kind of in the Midwest and upper Midwest, Ohio River Valley, and wherever you get HISTO. Usually, I don't see this much here. I mean, to be honest, I don't see retina. I mean, not a retina specialist, I'm a general ophthalmologist, but I can count the amount of HISTO patients I've seen in the last 30 years on one hand. I mean, I've probably seen three or four. It's a very uncommon, but you get these peripheral punched out lesions, and then you can get subretinal neon and macular lesions. All right, this is kind of weird-looking alley. What do we see in here? You're losing that nice little dimple in that reflex of the phobia, so what do you think could be going on in here? Eema. Eema. All right, so we look at it, and sure enough, this is something now with OCT. You guys may never see. I don't know, do you still have flourishing conferences? Do they still do flourishing at flourishing conferences? All right, so what have we got here? Gotta get that flower petal shape, and so this is classic HISTO and macular edema, and where did we say that the extra date is located? Henley's layer. Henley's layer, sure. There it is, all right, so there's Henley's layer, and sure enough, there's the extra date. We're in the macula, because the ganglion cell layer's more than one cell layer thick, and you can see here's the extra date in Henley's layer, so systoid macular edema. What's the most common causes of systoid macular edema? Diabetes could be, all right, so you get these to call it Irvine Gas Syndrome, so anything that causes breakdown, chronic breakdown of the blood aqueous barrier, eventually you get breakdown of the blood retinal barrier and you can get systoid macular edema, so it can be post-op, what else? Get it from VMT, traction, right? Yeah, good, exactly, so any kind of uveitis, any kind of chronic inflammation can give you systoid macular edema also, so most common things we see is, of course, post-op, because even if it's only in one or 2% of cataract patients that's still a large amount of people, but again, any uveitis, any inflammatory condition in the eye can cause this. Diabetics can get systoid macular edema. All right, boy, that's kind of subtle. Brad, what are we seeing here? We do this next one and that'll help you. That's bullseye. Exactly, so if you go back, sometimes bullseye's are hard to see, and so this is called bullseye maculopathy, and if you do florescine angiogram, now, is that leakage? No. What is it? We do an exact. Exactly, so you get these window defects, and so you'll get choral florescence showing up, and then this dark ozone around it, so what are some of the things that cause bullseye maculopathy? Plaquanil. Okay, so plaquanil's the biggest one now, because we see a lot of people on plaquanil, we worry about that. What else? Bullseye. Exactly, this should be, what are their medications? Hydroxychloroquid. Well, actually, old, old, old antipsychotics could cause this too. Old old antipsychotics and some of the older medicines they used to give people for depression could do these too. So the idea now with plaquanil is we see these people early, and we go ahead and we do a central 10-2 visual field in the center, we do OCT of the macula, we give new multifocal ERGs, we look for early signs because once it gets to this point, the damage is done, so again, the horse is out of the barn, that doesn't do any good to treat it there, so you want to prevent it, so I see a ton of plaquanil people in clinic that we do these testing on every year just to make sure. What do we see in here? So now, kind of these weird-looking streaks, those really aren't blood vessels, what the heck are those? Andruid streaks, or some people call them lacquer cracks, but so where do they occur? Where's the pathology? In Brooks, and so you get a little focal break in Brooks membrane, and these are called andruid streaks, and what's an entity, they always pimp you on boards that could cause this? This is called the plucked chicken skin on the neck. We don't pluck chickens, this is Pseudozathoma elastica, and so that'll cause andruid streaks, sickle cell can cause andruid streaks. What is this, Rachel? Real pale nerve, chalky white. And the vessels appear really attenuated. Really attenuated, what would this be? Exactly, so this is retinitis pigmentosin, if we look further in the periphery, you get what's called bony-spicule pigment, disruption of the pigment, why is that? Well, what happens is the degenerative RPE releases the pigment, the pigment deposits along the vessels, and so that's why you get this bony-spicule pattern. So here is the retin, that's really wiped out, and you get these pigment granules that are depositing around the vessels, so you get that bony-spicule pattern, and that's retinitis pigmentosin, RP. What do we see in here, Ali? Yeah, it looks like a sunny-side-up egg. What gives you that look to the macula? Best disease, and so this is one of those things, nothing else looks like this. And so I tell you, my favorite, Ray Faut was the pathologist in Baylor, he's from Cuba, he has a really good Cuban accent, and his favorite saying for a classic picture is, he's your brother in the train station. And you say, what the hell does that mean? Okay, you know, you go to the train station, you see thousand people, how you know your brother? Because only your brother looks like this. And so only is your brother in the train station, only best looks like this. So this is classic best disease, and you see this deposit of this material underneath the RPE here. What do we got here, Ariana? And so what does piece of form mean? Fish-like, so it looks like those little goldfish you'd eat when you were a kid, and the parents would give you to quiet down, so it kind of looks like those little goldfishes on here. So this is what we call Stargardt's disease, or fundus flava maculatum, and it's characterized by a deposition of lipofusum and pigment granules in the RPE. And so that is fundus flava maculatum. Boy, this is not out of focus, Mike. What are we looking at here? So... The media's really hazy, look, there's the disc. And there you see this little area here, and everything's there, it's foggy, so the goal is the headlight in the fog. What is classically producing the headlight in the fog? Seems like a richer sandwich with maybe a beer area. Well, but you wouldn't really see that whitening so much with a vitreous hemorrhage. So this is what that spot looks like when the vitreous clears up. That is active toxox, toxoplasmosis. And so toxoplasmosis, people probably get this, they can even get it congenally, get it as kids, these little toxocysts live in the retina, and then for some reason they'll activate. And so when you get the active toxa, you get a vitritus associated with it, so you get the headlight in the fog, and then eventually you get this area with these lacunar wiped out areas of pigment that's actually scleral showing through. So that's end-stage toxoplasmosis. When you look at the pathology, here's a little bit of RPE here, and then right where the toxa was, it just wipes out the RPE, wipes out the retina. And so sometimes you'll see, if these people get it activated, you'll see an old scarred lacunar area, and then you'll see this fuzzy area next to it where some of those cysts that have sat there dormant for years come back to life. So that's chronic toxoplasmosis. What could this be, Chris? This is probably some health factors. This kind of looks like a tomato ketchup bonus. Yeah, so people love to describe things with food, so tomato ketchup or pizza retina look. So this is indeed CMV. Now, I didn't, we didn't even know what CMV was when I was a resident, but there was this bizarre disease that these gay guys in California were getting. And so it turned out HIV, AIDS, one of the things you would get is you would get, you know, this chronic CMV retinitis. And so this is actually, again, it's blurry because I actually took this. So I took this as a resident. This is the first case of CMV we ever saw. And what you can see is CMV, it's interesting, it's like a lot of the others are RPE families. You can actually get intra, you know, nuclear and intracellular plasmid conclusions. So you get inclusions both in the nucleus and in the cytoplasm of the retinal cells. Now, fortunately now with people being treated with triple therapy, their immune systems are better, you don't see this as much. But still, even in immunosuppressed people, cancer people who are on chemotherapy, you can sometimes see CMV. And we say goodbye, this is the IMP's pyramid. And this here's that louver, you know, there's the louver there in Paris. It's an IMP's pyramid. And then you've kind of got, interesting, almost this kind of Roman, you know, arch coming into it, almost Germanic Roman, but this is all the Louvre right here and there's IMP's pyramid, which is now the new entrance. Okay, so next week is optic nerves. So no, you're optic nerves, okay? Questions? Well, two minutes over. So yep, you guys are really sweet.