White Spot Syndromes - Posterior Uveitis - Dr. Steven Cohen - 2026 04 10

I do this. Okay, I'm gonna look at you guys and talk. That way we have to pay attention. So, this is one of my favorite topics, white spot syndrome.

It's interesting. You guys have two books. I actually just bought the uveitis book. There's a 2025-26 uveitis book, which will be... Did you get your textbooks yet?

Oh, you did? Okay.

So the newest version. There's a 2026 uveitis book and then the retina book I think is 2024 or something. Ophthalmology is the only field that has that. It's kind of a blessing that we have an up-to-date textbook. Nobody else, no other fields do that. So it's really cool. There's a white spot chapter in both of these. So chapter 11 in the retina and chapter nine have almost exactly the same content. The interesting thing is book nine is the new book. So it's actually been changed slightly, which I find interesting.

So first of all, peripheral posterior uveitis, and just to step back a little bit, there's anterior, intermediate, posterior uveitis, and panuveitis. Posterior uveitis is... and when you do your uveitis, and you probably have been taught this, but it's not where... it's where the primary pathology is. Panuveitis is pretty rare. So panuveitis is VKH, sometimes endophthalmitis or panuveitis. Most other uveitides can be either anterior, posterior, or intermediate. So if you see someone with anterior uveitis with a little bit of cells in the vitreous, that's not intermediate, that's anterior uveitis. These are all posterior uveitis.

So when you look at posterior uveitis differential diagnosis, you got your white spot syndromes and then you've got some autoimmune disease like sarcoid, Behçet's, sorry about my voice, lupus, VKH, and sympathetic, and then masquerades and infection. So generally you have your non-infectious, masquerade, and infectious for all your uveitis diagnosis. In infectious, there's always... there's viral, bacterial, fungi, parasitic, masquerade, neoplastic and non-neoplastic. The thing we worry about is primary intraocular lymphoma, which we see sometimes. Have you had any here? Do you guys get them here? Yeah, they're pretty rare in the real world, but my partners, we do get some of these and it's an older population. And then non-neoplastic can be like trauma, drug induced, ischemia, or just hemorrhage.

So then we get to white spots. So what color is a healthy retina? Kind of what do you guys say?

It's like a trick question.

You know it's a very trick question.

There's no answer.

So the healthy retina is transparent, right? Because your receptors are on the... you don't think of it but you look through it, you see the choroid, you can't see the retina and you see the vessels on the... but you can't see the retina. So it's amazing, so it's remarkable that the body can make transparent tissue. That's all interesting about the eye, it's like incredible, biology can make a transparent tissue. So the retina is transparent and then the healthy RPE and choroid, those are what you guys were saying are red. So if you get a white spot, it's either a loss of retinal transparency, so anything that makes the retina non-transparent can be a white spot, and that's MEWDS is an example of that. So in MEWDS you've got your retina gets disrupted and you get white spots, and then anything that changes the color. So like a choroidal infiltrate and an RPE problem, and that's sort of what's happening.

I put these up because a close friend of mine whose son actually went through the program years and years ago, his sister. He told me when we first were meeting that he's got... he saw this retina guy and he either had MEWDS or birdshot. And all I could think of is they look so different anyway. So he can't have MEWDS or birdshot. So anyway, go through these.

So they're grouped this way. So there's a concept where there's the AZOOR complex, and I don't think they're grouped this way in the book but they should be. The AZOOR complex ones are MEWDS, multifocal choroiditis, panuveitis, PIC, and AZOOR. And those are all kind of photoreceptor problems. And then vascular, which interesting in the uveitis textbook, this is no longer in the white spot syndrome, but this... so in the future you're not going to have these, but for this lecture, you will. There's AMN and PAM. And then there's the block early stain late ones, which are probably more retinal pigment epithelial disease. That's AMP. And then there's the other ones which are probably more choroidal, which is birdshot, and then acute macular neuroretinopathy, I don't think should be in here but the uveitis book put it in here as a white spot that you're going to get it.

So MEWDS is the one you'll see probably one of the more frequent ones. It's young, young myopic females usually, pretty young, 28, teenagers can get it, women more than men. You can get a post-vaccine or a viral prodrome, but you don't always get the viral prodrome. So with all these viral prodromes, it's usually less than 50%. So the absence of a viral prodrome doesn't mean anything. And it's acute, painless vision loss and you get like photopsias, dyschromatopsia, and sometimes temporal scotomas. And I think one of the interesting things about MEWDS which is counterintuitive for a lot of diseases, it's unilateral, because you think... I don't have any idea why an autoimmune disease would be unilateral.

This was my sister's friend who was over our house. They were playing and she said she couldn't see out of one eye and I assumed she probably had multiple sclerosis with optic neuritis but I brought her in my office and she had MEWDS. So it was a 17-year-old female with two-week vision loss in her left eye, no prodrome, but she got a flu vaccine. And the vision right eye 20/20, left 20/60, it really drops down your vision. So what you'll see in this is... yeah look at that. So in the... you see these white spots. The big picture here which we've talked about some is the 55-degree FAF is like pathognomonic for MEWDS. So there's nothing that causes that pattern other than MEWDS. And then your fluorescein shows sort of the same findings as the FAF plus the nerve lights up and then your ICG shows all these dark spots. So that's why in that case you presented the retinal papillitis, I wanted the ICG to rule out MEWDS, which is very common. And then your OCT shows typical outer retinal atrophy in the center. And the other thing about MEWDS is all of this reverses, so generally most all of it gets better.

This was a 12-year-old I saw. This was a weird case because he had this yellow spot in the fovea and then all these white spots sort of around the side and a little bit of nerve swelling. And I was a little baffled by this and I think Janet Davis saw the patient too and just said, 'Oh yeah, that's MEWDS with a yellow spot. It's been described.' So you can get a yellow spot with MEWDS in the center. So it can look a lot like Best. I was worried about Best disease in the kid and he got better. I don't have the OCT from this. And so that's why the retinal pigment epitheliitis, a lot of the cases probably are just MEWDS.

Testing FA and then FAF give that wreath-like pattern. The wreath, I mean remember Dr. Pautler pointed it out to me once, is partly the lesions look like wreaths individually but they also kind of form a little wreath if you take the nerve and the macula. So that's the wreath and outer retinal atrophy, large blind spot, and the multiple dark spots on ICG. I get ICGs on my posterior uveitis patients. I think it's helpful to rule out things and rule in things. There are... this is sort of a photoreceptor, which I think is a good way to think about all the AZOOR ones. I think all the AZOOR ones are photoreceptoritides.

You get inflammation of your photoreceptor outer segment. It might be viral or post-viral and prognosis is excellent. You don't need any testing on these patients. I... there's no reason to test these patients. Your syphilis, I think for uveitis we almost always test for syphilis, but for a lot of these things that are pathognomonic, you don't need to do that. That's me, but we've talked about... we had it in conference. I haven't seen one lately. I think it's... yeah, I think it's influenza. I've seen one patient which we can never get published which seemed like it was publishable, who had three episodes of MEWDS after... the first one was after first flu vaccine, the second one was after second flu vaccine. So she said no more flu vaccine. So then she got the flu and then she got MEWDS again, which was interesting. So it was three influenza exposures because she had MEWDS each time.

And then multifocal choroiditis and panuveitis, which I think sort of diverts because I don't think this... I think this is a posterior uveitis but it's named multifocal choroiditis panuveitis. Mostly female. These can be older, 6 to 69 years old, but most patients are in their 30s. And then the thing... this looks exactly like histoplasmosis. So the big... this is a 35-year-old woman who's had... about 15 years ago had trouble in the right eye, four years ago trouble in the left eye, and these are... she has these scars. So it's multifocal scars and then this... she's starting to get this problem here.

What do you guys think that is?

In the left eye. This is new. This is her only good eye. And she's having vision loss.

Yeah. So, it's either CMV or it's a recurrent uveitis. So, and it's hard to tell.

Yeah. Yeah. Right there. So, that's good. Right there. So, it's either CNV. I think I decided... Oh, hold on. Pictures. Yeah. So, this is her fluorescein. It looks kind of... in the ICG, it would be nice if that was a little more striking to look like a membrane. So, I'm not sure this isn't inflammatory or... but I treated with a VEGF, got better. So, I think it probably was neovascular, but I've seen the multifocal choroiditis respond to both, either steroids or anti-VEGFs, and it seems almost random. It's definitely... the OCTA will be nice for this certain disease. OCTA is great for this I think and it's also great for CSR because sometimes CSR is neovascular and sometimes it's not.

So this is probably acute granulomatous... acute non-granulomatous... acutely there's non-granulomatous perivascular lymphocytic infiltrates and then chronically you just get atrophy, paravascular scarring. Common, you can have hundreds of lesions and it's required that they have some vitritis, otherwise it's just spots. They can get CME, macular vascularization, and then FA acutely get the hyperfluorescent early and leak late. And the differential is sarcoid, syphilis, TB, and the like. So these patients do need blood tests. So you would work up for sarcoid, not necessarily TB, and it's thought to be maybe Epstein-Barr, although I'd say almost everything's been linked to Epstein-Barr. I think Epstein-Barr finally got... there was some disease that finally was definitively linked to Epstein-Barr was... anyway.

So it wasn't... what's the one with the two different color eyes?

Yeah, that's valid. Okay, so possibly viral, immunomodulatory therapy appropriate in some cases, CMV and CNV as indicated, and the prognosis... There's a variant of it. I just... this lady finally came back to see me last month. She's 64. I've been treating her for 30 years, although not for the last 15 because she disappeared and her vision is 20/20. And then she also was seen by Alan Palestine up at the NIH and she's subretinal fibrosis syndrome. This is now her only eye because her other eye got so fibrotic and so starchy. The other eye was just so... so some of these cases develop this weird fibrotic component which is just miserable and they have to be on high dose... it's not very common.

That's bad. I presented at grand rounds. We used to have grand rounds here where we bring patients and she was one of my first patients I ever had in grand rounds. So long, a long time ago. Long time. It was kind of fun though. I think there's maybe a HIPAA thing now going where you can't just bring patients and drag them up to see them. I guess that's nice.

Punctate inner choroidopathy or choroidopathy. I think it's now choroiditis. So there's this new standard uveitis nomenclature working group which is trying to make uveitis a little more understandable and they call it punctate or multifocal choroiditis and they say it's a subset of multifocal choroiditis. So it's myopic females, 24 to 52, bilateral, same as the last one but they're smaller lesions. So they're 100 to 200 micron and it does look different to me. This is another one... G didn't think exist. He thought this... he said the same things. Multiple subretinal membranes are very common in these. That's why 40 to 75%... super duper. So this is a 34-year-old patient who had vision changes in the right eye eight days ago and she has a history of aches and pains. She's got sugar. She's on Plaquenil. Anyway, this is her two eyes. So these are more acute lesions. So these little white spots everywhere and you can see they're kind of small, a couple bigger ones I guess, and then this smudgy thing down here. So this was PIC syndrome and on fluorescein angiography they mostly kind of heat up. Again, this might be a neovascular membrane, probably active inflammation, but it's hard to tell. And on ICG they're dark, which is kind of interesting, except for this one. So that's why I think that one in this case probably is CNV. And they're much more numerous.

And they're small. So I... they really... I have a number of PIC patients and I don't have that many multifocal. I think PIC really is different. So again, possible etiology, same exact thing as the last one. Steroids or immunomodulatory therapy. Anti-VEGFs... steroids seem to work on these. Before we had anti-VEGFs, you know, in 2004, which is... well, we are... like you guys are actually younger than my kids. It used to be like I worked with people my age and then the people were my kids' age and now the people are all younger than my kids. Kind of scary. So the visual prognosis is good in the absence of CNV, recurrence is common, and this was final vision in a number of long cases. So a lot of patients can stay with good vision.

This was the only disease where I treated a woman through pregnancy with anti-VEGFs, which was pretty scary. We used Lucentis and I'm not 100% sure it didn't adversely affect... we talked about it some. Her baby did have a couple things because it probably wasn't related, but she had lost central vision in one eye and her other eye just wouldn't stop. It kept getting these lesions that kept flaring and flaring and flaring and we used steroids and she was on immunomodulators. The only thing that worked was mostly anti-VEGFs. So and she eventually tapered off.

And then AZOOR is uncommon. This is my only acute zonal outer retinopathy. It used to be more acute than it was. This was described before all the multimodal imaging. I think with all of our imaging now, not much is acute. Like acute macular neuroretinopathy, you just scan the macula. It's like, oh, it's a maculopathy. So acute vision loss of one or two zones. These are broader areas. It's zonal. It's usually unilateral initially but can get both eyes and some people recur and there's a mild vitritis. Although this is a patient I saw ages ago, a 25-year-old female, vision loss for two days. She had this white area in the middle so it's kind of a little bit discolored and then these little white spots that almost look like lesions. And she said there was darkness in her vision and no flashes or floaters. What you like with these patients is to get what's called a scintillating scotoma. So a dark area that... the MEWDS patients describe that scotoma that like shimmers, excuse me, that associates with photoreceptors.

And then three months later there was an area of atrophy here where the photoreceptors go. And then this is... then I've seen lots of patients, not lots, I've seen probably five or ten patients where the retina looks funny. You say, 'Oh, that was AZOOR a while ago.' And the way you can tell is because it looks exactly like retinitis pigmentosa, but it's asymmetric. So, this is a 60-year-old man with peripheral vision loss in the left eye four years ago, which is a little off because it's a guy and he's older, but maybe he didn't notice it. And yeah, and then this is a patient with a dystrophy. So, that's not easy. So, if you get an autofluorescence and it's symmetric, it's a dystrophy. If you get an autofluorescence that's very asymmetric, it's probably AZOOR in the past. The only exceptions being is that nowadays there's a number of carrier states for like choroideremia and stuff that are starting... we're starting to realize there's more pathology than we thought there was. But if you have asymmetry, it's probably AZOOR. I have a number of patients like that.

ERG is dysfunctional, visual field defects. OCT shows outer retinal atrophy. The fluorescein could be normal at the beginning and then the autofluorescence really shows areas that are abnormal. It's... oh somebody did a study of 25 patients. Anti-retinal antibodies are present in all these patients. So it's probably sort of a variant of an autoimmune retinopathy, which is not in this lecture. We show cases during the years on autoimmune retinopathy because I think that's more common than many of these. You can try steroids, you can try whatever you want. The prognosis is good for central vision mostly because it usually doesn't get everything. If it's in the center, you'll usually lose that vision, but it usually doesn't fill the center as much in both, especially.

So those are the AZOOR complex. So MEWDS, multifocal choroiditis, panuveitis, PIC, and AZOOR are all considered somewhat linked. And the reason for that is there's like Jampol, the fancy people, have case series where people get both. So the presumption is if they get multiple... if the MEWDS patient comes up with multifocal choroiditis, that's why they tend to link, sort of like twin studies. So if you see multiple diseases in a single patient, like those are probably connected.

These are the other ones. So these are... these are acute macular neuroretinopathy, probably won't be in this lecture when we give it again in two years, but it's the reddish-brown wedge-shaped lesions, petaloid, teardrop, mild vision loss, paracentral scotoma, which usually they can draw. So one of the things we used before we had all this... acute macular neuroretinopathy, you just have them draw a grid and they could say there's my lesion. In young white females, and it's thought it's ischemia from the deep capillary plexus. So this gets into the capillary plexi, epicapillary plexuses. These are the findings in a series of a bunch of patients from some paper back in... I didn't write the date here but it's a relatively old paper, but basically scotomas are almost always present. It's typically bilateral, sometimes unilateral, sometimes there's some association of infection, but the initial series, it was Dortman and somebody in 197-something, it was mostly women on oral contraceptives, but it's thought... and then epinephrine used to be like a dental thing after anesthesia vision loss. And so it's thought to be some sort of an ischemic episode.

This is a 40-year-old patient, no viral prodrome, 20/50 vision left eye, dire vision was... but there was a scotoma and she has lupus. She takes Plaquenil. This is one of these cases we... I try not to but people always get an IR because the OCT machines have IR. That's their wavelength. And the IR I think is really not helpful for almost everything except for acute macular neuroretinopathy where it's the best test. So the acute macular neuroretinopathy lights up on the IR. The rest of the tests are pretty normal. So your color picture, like there's a little gray spot if you know where to look. But honestly, these all look like spots. So that's a little bit off. The autofluorescence is normal, which is kind of cool because the macular pigment is in the axons of the cones which are unaffected. So your autofluorescence signal, the RPE is unaffected. Your cone axons are unaffected. So the autofluorescence is normal, your fluorescein is normal, your ICG is normal, but your OCT shows the lesion super well. And it's this deep lesion. So it's the deep capillary plexus.

It's associated with flu-like, COVID, oral contraceptives, and then some other lesions. It's a hypoperfusion of the deep capillary plexus and it gets the outer nuclear layer and photoreceptors. No treatments known to help and most people improve some and have improved a lot. It's interesting more people don't improve all the way. It's funny how some of these... I guess it's like a little stroke of your photoreceptor. So it's not necessarily reversible.

And then PAM. So PAM is very similar but just a couple layers up. So you get these parafoveal gray lesions, sunburst scotoma, paracentral inner nuclear whitening, and acute macular neuroretinopathy and PAM are very similar. This is an 83-year-old, not retired ophthalmologist, who came in with a spot in his central vision and he's got this typical PAM lesion. This is one of the only cases I have is just a PAM lesion, which is kind of interesting. So he has high cholesterol, his vision is 20/20, he's in really good health, and if you do all your testing, this does show up on the autofluorescence, which is interesting. So that's because it does clip those axons of the cones which is where the pigment is. And then although it's dark, I guess it just disrupts... your fluorescein doesn't show it because the fluorescein shows mostly your superficial capillaries, not your deep capillaries, but your OCTA shows a little bit of disruption there, although not a huge disruption, but it's not quite as normal as other areas. There's like a little area kind of cut out there.

You do see PAM in a lot of other diseases. So we always show... we show BRAO, CRAO, CRVO, and BRVO where you get... and so this is a CRVO, 56-year-old, sudden vision loss. Fluorescein, good circulation. There's a bunch of lesions, you see all these little guys here, acute macular neuroretinopathies. It's interesting, the PAM lesions are actually good. So the people with PAM lesions almost never have macular edema because there's something... so I think you get that... there's some thought that the PAM lesions occur in people with relatively good circulation in a CRVO, which... because I... then there was an older paper though where if you counted the PAM lesions it was bad. So the prognosis of PAM lesions in CRVO I think is still up for grabs but the recent papers I think suggest that they're actually good.

So the macular vascular anatomy, you've got your superficial vascular plexus is your ganglion cells. So that's what gets messed up with cotton wool spots. And then your deep vascular plexus is your inner nuclear layer, and the PAM is an inclusion of the outer. And the FA shows only the superficial. So and we do this in the first lecture, so we'll do this every year in August, we go over all this stuff, the different layers, all that. A, it's a lot to remember. It's a microvascular disease, cardiovascular risk factors, carotid disease, and ESR and CRP. I called him up, his were all normal, the ophthalmologist.

So the prognosis is usually good. And that's PAM. So AZOOR, PAM, and then the block early stain lates, which are not that common. So AMP more uncommon than serpiginous. I've seen it. It's just me, but my practice, I've seen a couple serpiginous, I think two AMPs. So you're unlikely to see these honestly. If you see an AMP, it's probably similar to... multifocal placoid pigment epitheliopathy, serpiginous, and then these other subdivisions which are kind of funny. I don't talk about those. I think these two are good and the other ones are probably just variants.

So acute multifocal... acute posterior... this is actually a P... acute posterior multifocal placoid pigment epitheliopathy. Acute onset, bilateral, gets scotomas again, about a third with flu-like symptoms, and then women are equally affected. This was a 24-year-old guy I saw some time ago. He was sick and then his joints started to hurt and he had headaches and then his vision started to change. And this is his right eye and his left eye and you can see these are... they're different, they're not white spots. They're pretty obvious. They're a little scary as far as a viral retinitis. I mean, if you see that, like that's a viral retinitis. This person's going to be blind and weak. But if it's AMP, he's in good shape. So then you do your testing because a viral retinitis would show this on the other test. So, you get a fluorescein and an ICG. Fluorescein, it blocks early and stains late, like super typical. So, this is early and late on the fluorescein. ICG blocks long. So, it's dark. And you see the spots there. And then the OCT shows this RPE outer retina problem.

This is a... I like these old videos, but it shows the disruption of the RPE. It's kind of funny. We don't show these like this anymore. It's just kind of pretty.

Yeah, I think the old... This is... I think it's on there somewhere. If you do the 3D view, okay, I don't know how you can spin it around, but it shows the... this person unfortunately did progress a little bit there. So, this was when he first came in. This was a couple years ago, right? This was 14 years ago. So, in August, this is August 24th, August 29th, and September 9th. And it just got more and more. The right eye ended up seeing poorly. The left eye spots got bigger and didn't quite get to the fovea. The good thing about AMP is despite disruption of the RPE, most of the patients see well, which is a little weird. So you'll see people... so later on, let's say you see someone in their 60s who said yeah something happened to me when I was in my 30s, the macula looks all pigmented, like they should be 20/200 but they're 20/20, that probably was AMP.

Yeah they drop but some of them are remarkably good. Yeah, but if they don't, but if they get a central lesion,