This talk will cover specific anterior uveitis entities, both infectious and non-infectious. We will start with the definition of anterior uveitis and discuss how to identify complications of anterior uveitis and discuss management of the uveitis and complications.
Lecturer: Dr. Ramana Moorthy, Associated Vitreoretinal Uveitis Consultants, Indiana, USA
[Ramana] Good morning, everybody. My name is Dr. Ramana Moorthy. I’m a clinical professor of ophthalmology at Indiana University School of Medicine and uveitis specialist. And today we’re going to talk about anterior uveitis entities. It’s a real honor for me to be here with you all. Let me just share my slides here. Some of you interacted with me on the Cybersight consult service. It’s based on some of these cases that I thought maybe we should review. The most common form of uveitis that we see in our practices, which is anterior uveitis. Meaning that the inflammation is in the anterior chamber. And this does require the use of a slit lamp biomicroscope, obviously, to determine the level of inflammation that you have. Uveitis can be classified most commonly anatomically where the inflammation is primarily located in the eye, for example in the anterior chamber, versus in the vitreous, versus in the retina and the choroid, versus all of those layers. And you can also classify the uveitis based on its onset whether it’s acute onset with red, painful photophobia versus chronic onset where the patient just has mild, blurred vision or maybe no symptoms at all but has significant structural damage to the eye. It can also clinically be graded as granulomatous versus non-granulomatous which is kind of falling a little bit out of favor, but when you describe mutton fat KPs or iris nodules, we think about granulomatous inflammation versus when those are not present, it’s non-granulomatous. But the most important classification could be still probably the separation between infectious and non-infectious uveitis entities. Which I think is really important going forward because it tells us how to treat things. In anterior uveitis the primary site of inflammation is the anterior chamber. Between the corneal endothelium and the surface of the iris, you need to use a two millimeter long, about 1.5-1 millimeter wide beam and grade the number of cells that traverse that cube, that volume of light that is shining in the anterior chamber. Intermediate uveitis, the primary site of inflammation is in the vitreous. We can sometimes view the anterior vitreous in the slit lamp, but we also look at this vitreous haze, et cetera, using the indirect ophthalmoscope to grade the uveitis severity in the intermediate uveitis case. And of course, in posterior uveitis, the inflammation is in the retina, the choroid, possibly the optic nerve and retina. And of course when there’s no predominant site of inflammation we call that a panuveitis. The other descriptors that we use to describe the uveitis also is important. If the uveitis is sudden onset versus an insidious onset. Hey this happened Friday night at 5 o’clock, I suddenly had redness, pain, and photophobia in the right eye, that’s an acute onset or sudden onset of uveitis, acute anterior uveitis. Versus somebody who says I don’t really know when things got, I started noticing floaters a few years ago, and the vision really got bad last month. That suggests that it’s more of a very insidious onset. And of course you can look at the course of an episode itself. If the episode duration is less than three months and you’re able to taper the patient off of medications and they don’t have recurrence of inflammation, that course, if it’s less than three months, it’s limited, if it is greater than three months it’s persistent. But if you have repeated episodes of activity off of treatment for greater than three months, you can call it recurrent, but if it’s less than three months between episodes and you can’t get the patient off steroids for more than three months before they flare up, most likely that represents persistent or chronic disease. And that’s very important because the treatment of chronic disease requires chronic therapy. Versus acute disease and limited disease where the therapy can be tapered gradually off. That’s very important from a vocabulary standpoint so we’re all speaking about the same thing. And this is all based on the standardization of uveitis nomenclature. We have the first poll question to begin with, this is pretty simple. A 25-year-old patient presents with subacute onset of blurred vision and light sensitivity in his right eye. Examination reveals ciliary flush, AC cell and flare, and keratic precipitates without signs of posterior segment inflammation. What is the working diagnosis, what would you call this? We’ll give you a few seconds here. Based on what I had told you earlier, the site of most of the inflammation is in the front of the eye. That’s right, anterior uveitis. Everybody’s awake, that’s good. If we have vitreous inflammation, somebody said vitreous inflammation, then we’d say well, maybe this is vitritis, intermediate uveitis like pars planitis, et cetera. Let me keep moving on here. This is a breakdown when we’re specifically talking about anterior uveitis, we’re now going to segway away from all of that general topic and talk a little bit more about anterior uveitis in specific. What are the signs and symptoms? We all know. Anterior uveitis, acute anterior uveitis is of sudden onset, pain, redness, and photophobia being the most common symptoms. In chronic cases, the onset may be either very insidious, meaning that they can’t tell you when the symptoms started. The patient may have no symptoms at all, they may have mild decreased vision, they might complain of a few floaters. But this is a longer duration. And of course when we look at the sign at the examination and look for the signs of uveitis, we’ll see in an acute case the eye’s going to be red. The patient’s going to be pretty uncomfortable when you look at him. They’re going to be very sensitive to light you shine from the slit lamp, they’ll be injection around the limbus, the peri limbal injection. There may be precipitates on the corneal endothelium. And these can be variable, they may not be very many. But you will definitely see anterior chamber cells and flare. And I’ll show you a picture of that in a moment. And you may see, if it’s really severe inflammation, a hypopyon. You may even see peripheral posterior synechiae or peripheral anterior synechiae if they’ve had previous episodes in the past or if this episode is very severe. Intraocular pressure is often low with a couple of exceptions in the infectious cases. For example, in infectious herpetic uveitis, anterior uveitis intraocular pressure is usually high. And of course in cases of toxoplasmosis also you may see elevation of intraocular pressure when there’s anterior chamber inflammation that spills over from the posterior segment. In chronic anterior uveitis, however, there’s no injection, the eye’s usually white and quiet. There may be KP sometimes there’s mutton fat KP, they’re more prominent usually. Usually there’s some sort of anterior chamber reaction. And here the flare may be fairly, especially with a chronic disease, there may be more flare. And the cellularity may be quite significant without causing any symptoms. And you may see posterior synechiae. The intraocular pressure may be all over the place but it can be elevated if it’s chronic disease and it’s not been very well controlled. This is a really good picture from my colleague Dr. Cunningham who sent me this. It’s a beautiful slit lamp photograph. And I use this to remind everyone what are we looking for? What are we looking at that anterior segment? In this case you have this patient, we’re looking at the anterior segment photograph as the slit beam, which is about two millimeters by a little over half a millimeter in width, maybe close to one millimeter in width. That light beam traverses the anterior chamber from the corneal endothelium. And you can see there’s a beaten metal appearance to the endothelium of the cornea suggesting that there may be some corneal edema here. Just as an aside. And of course in the anterior chamber you see the Tyndall effect which is the flare, which is the solidity to the beam itself. And then you see the small white dots which are the inflammatory cells. This patient has no hypopyon, I would grade this, in my opinion, this is about a 3-4 plus inflammation. Again, I know that there’s a little diversity and there are specific scales that you can use. But in practice it’s very difficult to sit down and actually count individual cells. You don’t have time to count all the 150 cells versus 125 cells or something. I think most of us have in our mind what we think is one plus, two plus, three plus cells. According to the standardization of uveitis nomenclature, if you see no cells in there you put zero. But if you even see one cell floating around in the eye, it’s not zero, the rating would be 0.5 cell. And I do use that. Sun classification I typically will use a sun criteria to describe my uveitis and describe the flare and cell. And this is a modest amount of flare, about a two plus flare. And there’s various degrees and grading of flare that we can use. This is another example. On the left you see acute anterior uveitis, there’s limbal injection in the conjunctiva and you see the presence of this hypopyon. And on the right side you see more chronic disease. This is the patient who had sarcoid uveitis who had developed posterior synechiae in multiple locations, has small iris nodules here at about 10 o’clock you’ll see some. And this person had a white and relatively quiet eye with longstanding inflammation with anatomic structural damage from the inflammation. We talked briefly earlier about non-granulomatous versus granulomatous. I’ll only mention here that if there are large nodules and evidence of granulomata in the uveal tract in the iris and the posterior segment, et cetera, typically that leads us towards the diagnosis of thinking about granulomatous inflammatory diseases such as sarcoidosis, or tuberculosis, et cetera. The presence of KPs, usually fat, greasy KPs are called mutton fat KPs, and when they go away they can leave these crenulated ghost KPs. Sometimes they can be pigmented. The nodules on the iris have different names, Busacca nodules are the ones that actually form on the stroma of the iris. And the Koeppe nodules are the nodules that form on the margin of the iris. Again, these are descriptors, not crucial, but it helps you a little bit in terms of what you think. This is an example. The patient on the left has Koeppe nodules on the iris margin, you can see. But they didn’t have, sorry, this patient actually just had idiopathic anterior uveitis. The one on the right, actually, you see pictures of very big mutton fat KPs. There’s significant inflammation of the iris, there are numerous iris nodules both on the margin of the iris, Koeppe nodules, and also Busacca nodules. And there’s actually infiltration of the entire iris with a lot of inflammation. This patient had very fulminant sarcoid panuveitis with a lot of anterior uveitis as well. Here’s another example of an acute non-granulomatous uveitis on the left, which is a patient who was HLA-B27 positive. He had a hypopyon on the left here, severe conjunctival injection. You can see even the iris margin vessels are inflamed. There is 360 degrees of posterior synechiae. There is a fibrin membrane that’s keeping that iris from dilating. And you’ll see that this patient really doesn’t have KP, she’s got a lot of flare and a lot of cells. I’m sorry that these keep skipping. And then on the right side you’ll see a picture of these mutton fat KPs. I wanted to show an up close view of that. Again, these are KPs that are part of the granulomatous, typically chronic inflammatory disease. This is a patient that had sarcoid on the right. Let’s talk a little bit about specific anterior uveitis entities. And I think the way to break it up in my mind is to think about those that are more acute onset and then there’s more that are chronic that we can describe into disease entities. I wanted to specifically talk about these because the vast majority of what we see when we do a laboratory work up looking for causes of uveitis and do a review of systems, the vast majority of time we’re not going to find an unlying cause. In my practice, which is a tertiary uveitis practice, even in that setting typically my lab tests are positive maybe 25% of the time, 30% of the time, maximum. ⅔ of my patients won’t have an identifiable cause for ocular inflammatory disease. And that’s based on a very thorough history as well as laboratory evaluation based on what the history and examination reveal. Let’s talk a little bit about acute anterior uveitis. First is the next poll question here. A 36-year-old man presents with a second episode of acute anterior uveitis. First episode was in the right eye, the current episode is in the left eye. Which of the following laboratory tests are unnecessary? This is a little bit of a segway into lab testing. What would you do to test this person? This is his second episode of anterior uveitis, first one was in the right eye, now the left eye is involved. What tests would you NOT order? You could order many tests, very expensive. Maybe not even available. What would be the most useful thing to do without any other history. I would probably get a really good history on a patient and then order a test. Let’s see what you guys say. It’s all over the board. Yeah, I think that a lot of you guys said antinuclear antibody testing. Let me tell you, first of all, what are you going to get when you get that? Almost always everybody gets 1-80 speckled for their results. What do you do with that? I don’t know. I don’t know what you do with that. Does that person have lupus? Does lupus cause acute anterior uveitis? I’ve not seen that. Lupus can cause retinal vasculitis, it can cause scleritis. But it’s very rare that lupus and lupus rarely can, in the case of very severe nephritis, can cause choroiditis too. But it’s extremely rare for it to be associated with anterior uveitis. Now there may be one scenario where a patient with anterior uveitis, you might do an ANA testing and that’s in a child who you suspect may have juvenile idiopathic arthritis. But this 36-year-old man likely has HLA-B27 positivity and HLA-B27-associated disease. He’s had acute anterior uveitis with recurrent episodes affecting both eyes, sometimes only one eye’s affected, but both eyes. And I would check him. I would do tests on this patient. HLA-B27 check for that and check for a serologic test for syphilis, especially a Treponemal-specific test. Not RPR, but either an FTA or a I would do a MHA-TP or anti-Treponema IgG antibody testing. It’s very important that you test for syphilis or HLA-B27. Those are the two things. Chest x-ray, I don’t know that I would get that unless the patient has other things that suggest that he may have TB or sarcoid. But I would not get an antinuclear antibody testing in this patient. I’m going to skip these because we’ve covered these ad nauseum. Let’s see here. In an acute anterior uveitis setting, the history is of sudden onset of pain, redness, photophobia and the patient may or may not have decreased vision. And the most commonly it’s unilateral, it may be recurrent or it can be sequential involved with the fellow eye. There can be periods of disease quiescence off treatment. Typically more than three months in duration. If it’s unilateral and you see acute anterior uveitis, you think about other possible infectious causes, especially if the intraocular pressure is elevated, such as herpetic disease. If it’s bilateral or simultaneous you think about other things and we’ll touch on these a little bit here of tubulointerstitial nephritis and uveitis syndrome for example. Or the patient may have post streptococcal inflammatory disease. There are many things to potentially consider in the diagnosis. The features, we already talked about a lot of these. If there’s a hypopyon in acute anterior uveitis, likely you’re dealing the HLA-B27 positivity. And if you suspect that you may want to do a more focused review of systems. Have you had arthritic, achy joints, red, swollen joints? Dyshidrotic skin rash on the palms of the hands or soles of your feet? Any problems with chronic lower back pain? Migratory arthritis, different joints involved, or do you have inflammatory bowel disease? Do you have psoriasis, do you have skin lesions that suggest psoriasis? All of those will lead you towards the diagnosis that the uveitis is related to HLA-B27. Randomly ordering HLA typing isn’t very useful because if somebody has choroidal inflammation and you order an HLA-B27, remember that 5-8% of the population at large will be B27 positive, so it doesn’t particularly help. Posterior synechiae may be common in this disease anterior uveitis. There may be some spillover of cell into the anterior chamber. Remember when you look at the vitreous under the slit lamp, you may see cells spilling over from the anterior chamber if the inflammation is very severe, into the vitreous, into the anterior vitreous. As you follow the vitreous more posteriorly on the slit lamp, using a ruby lens or directly observing, you’ll see that the cells trail off. They don’t get worse posteriorly and that tells you this is just a spillover from the anterior segment inflammation. Sorry, I apologize for my cursor here. I think my mouse is moving the slides. Again, intraocular pressure in the most cases of noninfectious anterior uveitis is going to be lower with acute anterior uveitis. Again a review of systems is very important. I already mentioned a lot of these before, skin rashes. Asking about a lot of things that potentially could lead you to systemic diagnosis. And in the case of acute anterior uveitis, my review of systems is almost always pointed towards seronegative spondyloarthropathies. Namely HLA-B27 positive-associated disease. There may be other situations where I may ask about mucous membrane lesions in the mouth or genitalia if I’m concerned about Behcet’s disease. But again, this is based on clinical appearance and a history that the patient gives. I’m going to move on here. Obviously in addition to the eye examination, examination of the extremities, hands, skin, spine flexibility, inspection of the mouth, those kinds of things add significantly to understanding the nature of what’s causing the inflammation. And laboratory evaluation, again, syphilis IgG, anti-Treponema IgG and HLA-B27, those are really important. If the patient has bilateral cases and they’re relatively young and bilateral anterior chamber inflammation of acute onset, I often think about the possibility with tubulointerstitial nephritis and uveitis syndrome. This has become more common post-pandemic. I’m not sure exactly why. We thought that at one point that maybe a viral etiology but there is a very strong association with this HLA solubilized DRB1 0102. You can check for that if you have the capacity in your laboratory. But you can also check for a urinary Beta 2 microglobulin which will be elevated with the interstitial nephritis that often accompanies this uveitis. This is a case of a patient who developed a very severe, what I call a hyperacute anterior uveitis. Presented with a sudden onset of severe pain and very blurry vision. And you can see intense, that’s not corneal edema, that haze is all fibrin in the anterior chamber. It’s a plasmoid aqueous. And there’s a congealed small hypopyon inferiorly. If you see somebody like this the first thing on your mind should be, oh, this looks like HLA-B27-associated anterior uveitis. This is a 28-year-old patient that’s never had trauma, never had surgery or anything. That’s something that you need to think about in an acute anterior uveitis presentation. This is an image you should put in the back of your mind, this is how it looks. And the other one I showed you before is with the hypopyon. Here’s what happens after you treat this patient with periocular corticosteroids, oral steroids and topical steroids, very intensive therapy. The fibrid flap contracted, the posterior synechiae broken, the vision is normalized. And this patient had at presentation also this with this psoriasis. And he was HLA-B27 positive. He also had psoriatic arthritis. You don’t have to, you can just have cutaneous psoriasis, HLA-B27 positivity, and anterior uveitis. These are the seronegative spondyloarthropathies. These are very important groups to consider in the differential diagnosis of acute anterior uveitis. And probably represent the most identifiable causes of acute anterior uveitis, especially acute hypopyon acute anterior uveitis that is non-infectious. Other things to consider in the differential include infectious causes such as syphilis, herpes, and of course if you have a hypopyon in a patient who’s postoperative 3-5 days after cataract surgery, you need to rule out endophthalmitis first and foremost. That’s why this is in the differential. Other things like Behcet’s disease and sarcoid are really based on clinical history and the completion of the rest of the eye examination and posterior segment findings. Trauma can cause iritis in the differential. The intraocular lens can, and we’ll talk about this in a moment. Drug-induced inflammation which I’ll talk about as well, and tubulointerstitial nephritis and uveitis syndrome. How do you treat patients with acute anterior uveitis? Obviously you use topical steroids, you start very frequently, usually every hour, and gradually taper. Even with moderate inflammation, let’s say they had two plus cells, it’s a mistake to put the patient on three or four times daily prednisolone and expect that they’re going to get better and then when they come back they’re worse and you find that you have to increase the medication. What you want to do is to start high and then taper, just like you would with oral steroids, similarly with topical corticosteroids you want to do the same thing. Cycloplegia, depending on the severity of the inflammation. If the inflammation is mild to moderate, I often use cyclopentolate. If the patient has very severe inflammation like the fellow like I showed you with the HLA-B27 plasmoid aqueous, I would use atropine or hyoscine, 1% atropine is typically available for me to use. And I usually use that often, as frequently as four times daily initially to really get the pupil to open and break the posterior synechiae when I’m using intensive topical steroids. Recently in the last five years, difluprednate, which used to be Durezol, now it’s generically available, difluprednate has been utilized too. It is twice as potent as topical prednisolone, it’s a topical agent. It’s not a suspension so you don’t have to shake it up to put it in. It has high bioavailability into the anterior chamber. And I really think that it’s an excellent drug used acutely. But it’s not a great drug to use for chronic maintenance therapy because many patients, and in children up to 50%, can develop a severe steroid induced intraocular hypertensive response. The intraocular pressure can become very high with chronic use of difluprednate. Typically the most available topical steroid drops for most of us is prednisolone. But if the inflammation is very severe one option that we have instead of oral steroids would be to use topical difluprednate. There is an advantage to using these topicals when you haven’t completely ruled out the possibility of an infectious cause of inflammation. Many times when you look at somebody who has inflammation, you can’t tell is it infectious, is it non-infectious just by looking if it’s just anterior chamber inflammation. But the clues are there. The clues are based on the exam and the history. In addition for a severe attack, as I said, periocular corticosteroids, oral corticosteroids, and even intravenous pulse corticosteroids can be used. And with chronic disease we may end up having to use immunomodulatory therapy. There are many complications of disease which we’ve mentioned already. Posterior synechiae and pupillary seclusion which may become chronic and the patient can develop iris bombe and secondary angle closure. Peripheral anterior synechiae can result in secondary angle closure as well, chronic angle closure glaucoma. And glaucoma, intraocular pressure elevation can develop acutely or chronically. And then cataract formation with chronic disease especially or with excessive corticosteroid use. And chronic inflammation can result in cystoid macular edema, epiretinal membrane formation can also develop. And with very, very severe advanced disease with more chronic disease you can develop hypotony. Acute anterior uveitis rarely presents with hypotony. One case that you may keep in mind is Cidofovir induced anterior uveitis. That can be associated with profound hypotony because Cidofovir, an antiviral that is used to treat CMV retinitis can produce this. And it can also produce anterior uveitis. That’s something to keep in the back of your mind for a future test question, perhaps, that you may answer. Drug-induced anterior uveitis is important to consider as well because Rifabutin can produce a hypopyon uveitis, can look like HLA-B27. Bisphosphonates produce an anterior uveitis or even scleritis in some cases, non specific kind of findings. Brimonidine, topical brimonidine produces a granulomatous anterior uveitis with a follicular conjunctivitis and elevated intraocular pressures. This is something to keep in the back of your mind of glaucoma patients who are on chronic brimonidine. Prostaglandin analogs have been associated with anterior uveitis and CME. And I mentioned earlier Cidofovir which is rarely used now and can cause hypotony and anterior uveitis. Those are drug induced. Here’s a case of a Rifabutin-induced hypopyon uveitis. You can see that less than one millimeter sized hypopon in this patient. This patient presented with not that much inflammation, but fairly severe inflammation and vision loss and responded very nicely to adjusting the dose of the Rifabutin and then using topical steroids. Here’s a patient, this isn’t a subconj hemorrhage, this is actually a patient that’s got fairly severe anterior chamber inflammation and scleritis related to zoledronic acid which is a bisphosphonate infusion for osteoporosis. Here is a patient who had bilateral, a long history of primary open angle glaucoma who was on topical brimonidine and presented on brimonidine with pressures of 30 in each eye with granulomatous KPs like this. They also had follicular conjunctivitis. This is a patient who has inflammation related to brimonidine. The brimonidine was stopped, topical steroids were used for a short period of time and the inflammation resolved. We’re going to move on now and talk a little bit about another condition. Let’s see if you guys get this right. This is a poll question. A 14-year-old girl complains of sudden onset of bilateral eye pain and photophobia. On ocular examination she had bilateral anterior uveitis and had a fever for two weeks, modest flank and abdominal pain, weight loss of 10 pounds. She’s not feeling well. Her sed rate was 80, she had a mild elevation of serum creatinine and mild proteinuria. What is the most likely diagnosis? Let’s see what everybody put. Okay, yeah. That’s right. It’s tubulointerstitial nephritis and uveitis syndrome, that’s the most likely diagnosis here. We’re talking about a 14-year-old, bilateral acute anterior uveitis. This condition, sorry, I don’t know what it’s doing here. The TINU or tubulointerstitial nephritis and uveitis syndrome has been increasingly recognized as an important identifiable cause of bilateral ocular inflammation. Usually patients are younger. But I have seen patients as old in their 50s present with this condition. And there may be association with medications and infections. There may be a genetic predisposition with that HLA-DR 0102, I mentioned earlier, associated with this. But the acute interstitial nephritis component is self-limited usually and what’s left over is the uveitis. The uveitis becomes chronic and difficult to treat. There may be other causes of renal inflammation that cause uveitis that may need to be ruled out, of course, including systemic lupus erythematosus. But again, lupus typically doesn’t present with bilateral anterior uveitis. Sarcoid can cause renal disease occasionally and then GPA of course, Wegener’s, but that usually presents with retinal vasculitis or scleritis. And other systemic infections could, we talked about Lyme’s disease, we mentioned those things we talked about. There are other infectious causes of nephritis that can also cause this. But generally there’s little or no history of systemic systems even though our case had a lot of things. But there may be some mild febrile illness and there may be a flank or abdominal pain. And the patient usually will have pain, redness, photophobia, and inflammation usually in both eyes. In my experience, the inflammation is not just in the anterior segment, where it’s predominant, but there may be some vitritis as well. You may see an intermediate uveitis and/or a fairly severe anterior uveitis combined with a little bit of intermediate uveitis. It’s usually non-granulomatous, you may not really see a lot of mutton fat KPs but they have been described. You can see usually hypopyon is very rare, you can see other forms of uveitis with this condition but bilateral anterior uveitis is probably the most common anatomic form of inflammation that’s been reported. It is recurrent or chronic in more than half the patients the uveitis is. And this patient when the nephrologist evaluates this patient, typically the proteinuria may be gone because it’s so self-limiting. It’s very mild, it’s not going to cause nephrotic syndrome. It’s usually less than 3.5 grams a day. And the patient will have an elevated urinary Beta 2 microglobulin which may remain elevated for several weeks or even a few months while everything else returns to normal. This is something a nephrologist probably should look at. But again most of the time they don’t have to do much. It’s us as ophthalmologists to have to take care of the inflammatory disease in the eye. I mentioned the HLA-DRB1 0102 haplotype that is associated with this disease. And I already mentioned the differential. The treatment is the same. Usually topical steroids, cycloplegics. In more severe cases, the posterior segment or intermediate segment involvement we’d have to use systemic corticosteroids. Immunosuppressives sometimes have to be used with these cases and I have a couple of people who have TINU who are on immunomodulatory therapy with Cellcept. The complications are the same as with other ocular inflammatory diseases of the anterior segment. You can see anterior segment complications which is cataracts, posterior synechiae, cystoid macular edema, glaucoma, all those things. Next question. In a non-immunosuppressed adult with chronic bilateral anterior uveitis, which of the following laboratory examinations is most likely to be helpful? So it’s a chronic bilateral anterior uveitis, which is the most likely test that’s going to be useful to you that may provide some answers? Chronic bilateral anterior uveitis, what causes that? The answer that I was looking for is chest x-ray and serum angiotensin converting enzyme level. Why? Chronic bilateral anterior uveitis can be sarcoid. Is it going to be toxoplasmosis? No. toxoplasmosis is a retinochoroiditis with some spillover of the anterior chamber. It’s usually unilateral. And HLA-A29 positivity you’re thinking of birdshot retinochoroiditis. Usually these patients will have posterior segment disease. They’ll typically have no anterior chamber cells. And rheumatoid factor is not useful. Rheumatoid arthritis, if you’re going to check for that, causes what? Scleritis. It may cause in some severe cases occlusive retinal vasculitis that they have anti-citrullinated peptides. If they have antibodies to CCP then you potentially could have vasculitis. But I’ve not seen anterior uveitis present where we would need to check a rheumatoid factor. Now, if it was a five-year-old patient that presented with anterior uveitis bilaterally and it was insidious, and looks like there’s some chronic disease, I would probably check an antinuclear antibody and rheumatoid factor. Those are the only times I would check those two tests in a patient for a uveitis workup. An antinuclear antibody, rheumatoid factor is really not useful for anterior uveitis workup except in the case of a child where you’re suspecting they have juvenile idiopathic arthritis. So a chest x-ray is very useful. Which of the following features is most consistent with the uveitis in pauciarticular juvenile idiopathic arthritis? Intermediate uveitis with snow banking, bilateral chronic anterior uveitis, chorioretinal scars, or diffuse stellate KPs? What kind of uveitis would you see in pauciarticular juvenile idiopathic arthritis? I’m noticing this assumes that you’ve had some information about uveitis already because I assume most of you have. The right answer is yes, chronic bilateral anterior uveitis. That’s what you see in pauciarticular JIA-associated uveitis in young girls in particular. Let’s move on here. There’s another question. Which one of the patients with juvenile idiopathic arthritis is at highest risk for developing chronic anterior uveitis? In other words, which one do you have to watch the most closely? A 12-year-old male who is ANA negative, rheumatoid factor positive with polyarticular JIA? A 4-year-old female with ANA positive, rheumatoid factor negative pauciarticular JIA? An 8-year-old female with ANA positive, rheumatoid factor systemic onset JIA or Still’s disease? An 8-year-old male with HLA-B27 positive, ANA negative enthesitis? Which patient will have the highest risk for developing chronic anterior uveitis? This is important for you to understand the international as well as our US classification of JIA because it tells you how you need to follow these children. And the right answer is the pauciarticular is number B, the patient who is ANA positive, rheumatoid factor negative with pauciarticular JIA. That patient is at greatest risk for developing chronic anterior uveitis. Number four the second highest risk, that patient 8-year-old male, HLA-B27 positive, ANA negative enthesitis. That patient can develop a HLA-B27 like hypopyon anterior uveitis. Persistent or chronic inflammation in the anterior chamber can be very insidious in onset, may be asymptomatic, the duration is at least three months. And again the symptoms, the signs we’ve already covered a lot of this. Conjunctiva may be white, you may see nodules in the conjunctiva if they have sarcoid, and those nodules can be biopsied to make the biopsy proof of sarcoid. There may be keratic precipitates that may be significant and evidence of old KPs. There will be cell and flare. The flare may be significant even with few cells with chronic disease. Iris nodules may be present and posterior synechiae and peripheral anterior synechiae may be present. This is a patient with persistent chronic inflammation. They have Koeppe nodules along the iris margin here. This patient did have sarcoid. Here is another sarcoid patient with much more obvious evidence of that, we showed a picture of the previous with mutton fat KPs, Koeppe and Busacca’s nodules, and granulomatous inflammation of the iris. A detailed history is really important. And the age of the patient will also help you. 4-year-old when you’re seeing chronic inflammation, you need to ask about joint pain, joint swelling, red, swollen joints, difficulty walking, difference in behavior, and how they’re playing and et cetera in the child. And then of course we’ll do the typical laboratory work up. The laboratory work up that I always tell people, the basic work up that you should do in any person that you’re working up for uveitis is to rule out sarcoidosis, syphilis, and tuberculosis. Sarcoidosis is a histopathologic diagnosis based on the diagnosing noncaseating granuloma in various ocular tissues or various body tissues, excuse me. A chest x-ray can be informative but not diagnostic. Chest x-ray and then a PPD skin test and/or interferon gamma release assay, do a check for TB. Angiotensin converting enzyme level, lysozyme level. Not sensitive or specific but maybe suggestive and can be useful in the presence of positive chest x-ray finding, along with clinical findings that you see on the ocular examination. Those are the testings. And then, of course, everyone should have anti treponemal testing to specifically, syphilis IgG or MHA-TP or FTA. These are treponemal specific tests to rule out syphilis as a cause. The rest of the work up, as I said, is guided by the age of the patient. For example, as I mentioned earlier a pediatric patient with chronic anterior uveitis, you’re going to check an antinuclear antibody and you’re going to check a rheumatoid factor because that will help you classify the patient. And the pediatric rheumatologist will definitely do that as well. There are many things that we consider in the differential diagnosis of chronic iridocyclitis. Local ocular diseases include Fuchs and then of course with unilateral disease with Fuchs, viral herpetic anterior uveitis. We can also see anterior segment inflammation that spills over from the posterior segment. This is rare, but this can happen where the posterior inflammation or vitreous inflammation is very severe, you may see a few cells spill into the anterior chamber. The anterior chamber inflammation is just secondary rather than a primary problem. And that’s in the differential diagnosis of anterior uveitis. There are many systemic diseases that may be potentially you can think about in the differential diagnosis. MS, sarcoid, TB, syphilis, all these. MS typically will be associated with intermediate uveitis and retinovascular inflammation and pars planitis. It’s really not, we don’t see much in the way of anterior segment inflammation with this. Sarcoid can present with any form of inflammation in any part of the eye. And tuberculosis similarly can present in anterior, intermediate and posterior, and panuveitis. Syphilis the same way, the great mimicker. Inflammatory bowel disease, juvenile idiopathic arthritis, all are in the systemic causes of inflammatory and infectious causes of inflammation that we see. Chronic iridocyclitis is treated with topical steroids chronically. Everybody wants to taper patients off of steroids. I understand, but chronic diseases have to be managed chronically. You don’t treat diabetes for one day and say it’s cured. If somebody has chronic inflammation, if they have inflammation for six months, that inflammation inside their eye is not going away. They may need chronic maintenance therapy with corticosteroids. They need chronic cycloplegic therapy usually with a mild cycloplegic like cyclopentolate indefinitely to prevent posterior synechiae formation long term. Chronic use of corticosteroids we need to monitor for intraocular pressure elevations. We can also treat with regional and even intraocular corticosteroids if we know that the chronic inflammatory disease and the result in cystoid macular edema, for example, is not infectious in etiology. It’s very important to rule out infection before you go to more aggressive treatment beyond drops for anterior segment inflammation. And you can use systemic therapy for really hard to treat bilateral and chronic anterior uveitis and oral prednisone. And of course corticosteroid-sparing agents are utilized quite commonly in this disease process. The chronic iridocyclitis that’s bilateral is probably the most common and most frustrating thing that I see in my practice on a day-to-day basis. It’s idiopathic, work up negative and I’m struggling to try to get the inflammation controlled to control cystoid macular edema, control glaucoma, and address cataract. Those complications and prevent the patient from becoming blind from those complications. That’s what I’m trying to do. And so you can see many forms of glaucoma with this including open angle glaucoma, closed angle glaucoma because of structural damage, and combined mechanism glaucoma with chronic disease. When you get to very late stages of disease the eye can become hypotenous and that’s a very severe problem. Obviously in that situation you have cyclitic membranes that develop that cause the ciliary body to become atropic and non-functional. And treatment of hypotony can be very, very difficult and usually in many times it’s fruitless. You can develop atrophy, complications with the cystoid macular edema I already mentioned, band keratopathy, cataract formation. One of the most important facets of chronic anterior uveitis that’s bilateral is juvenile idiopathic arthritis. It’s really important for us to recognize this and prevent blindness because this affects children. And so this has been a very important part of most uveitis specialist’s practice, how we screen, monitor, and evaluate patients who are young who have anterior uveitis. JIA is the most common form of chronic arthritis in childhood. Usually patients present before the age of 16. And they usually have persistent arthritis for more than six weeks. You can see the prevalence and incidence is not that uncommon. You’ll see if you have a city of a million people, you’ll have probably 100-200 patients who have this condition. Most common systemic association with iritis is JIA in children. If you have somebody who has chronic iridocyclitis who’s a child, you need to be making sure that they see a pediatric rheumatologist and be appropriately evaluated for underlying juvenile idiopathic arthritis. Again, look at the tertiary care setting. A third of patients we see have this as the cause of the inflammation. There are many different classification systems. I think it’s most important just to remember that the pauciarticular where you have less than five joints or so involved, versus the polyarticular disease is how we separate the two. And the pauciarticular, the one that we have fewer joints involved are the ones typically are going to be at higher risk for developing chronic anterior uveitis. There’s the systemic variety or used to be called Still’s disease, the oligo or pauciarticular varieties, and then the polyarticular varieties that have rheumatoid factor negative and rheumatoid factor positive. And then the psoriatic arthritis and then we have the enthesitis, usually these patients are HLA-B27 positive and they have involvement with tendons and other soft tissues around the joint. And then there’s an undefined group that doesn’t really fit. They have all the characteristic features of chronic uveitis but nothing else going on in their joints or anywhere else in the body. The uveitis risk is greatest for those who have oligoarticular disease, this is important to remember, and especially those who are ANA positive and girls. Those are the highest risk. If you have somebody who has oligoarticular or pauciarticular JIA and they are ANA positive and they’re 4 years old and they’re rheumatoid factor negative, that person is at very high risk, probably in the 30-40% chance of developing iritis if they don’t have it already. And chronic iritis at that, it will be asymptomatic and difficult to visualize unless you put them in the slit lamp and take a look. You won’t be able to see that just with an indirect ophthalmoscope or eyeballing the patient. The other conditions are less likely to cause it. The psoriatic arthritis can present with inflammation as well but usually it’s more acute. Although there can be chronic disease with this as well. And enthesitis as I mentioned with B27 positive, usually have acute recurrent episodes of uveitis. I already mentioned the oligoarticular here, four or fewer joints, so less than five joints within six months of presentation. Again females are more commonly affected. ANA positive in 85%, rheumatoid factor negative and uveitis is frequent. About ⅓ develop anterior uveitis in their first four years of life. Polyarticular, a little bit less common the risk of uveitis. I won’t bore you with the details of all of these. Here they have more than four joints involved typically. Again a preponderance of girls that are affected. It resembles oligoarticular disease but the psoriatic arthritis is slightly different in that there may be significant changes in the nailbed and other things that lead you to the diagnosis of psoriatic arthritis that will help. HLA-B27 positive enthesitis we already covered. Usually these patients present with recurrent bouts of acute iritis that can be managed, typically episodically. Sometimes these patients do go on to need chronic therapy but that’s rare. And polyarticular disease typically does not, and rheumatoid factor positive polyarticular disease usually not associated with uveitis. Although it can occur, it’s rare. And systemic disease is unlikely to be associated with uveitis again, it’s pretty rare. I’ve already mentioned the risk factors. Remember the oligoarticular disease, rheumatoid factor negative, ANA positive, girls, age between two to five, those are the risk factors, those are the patients that need to be monitored very closely. And these are the monitoring criteria that have been developed by international as well as national US organizations in terms of JIA monitoring for iritis and anterior chamber inflammation. And this requires slit lamp examination. Those patients with oligoarticular disease that are ANA positive, that are young, that are at high risk, they need to be checked every three months. The ones that are moderate risk every six months. If they don’t have inflammation obviously. If they have inflammation then you have to start treating them and the treatment usually involves topical agents, followed by institution of systemic immunosuppressive therapy, and often biologics fairly quickly in the course of treatment. The uveitis associated with oligoarticular disease is asymptomatic. There’s usually painless loss of vision if it goes long enough so it’s really difficult. What you want to do is not see a patient like this who has end stage disease, who’s eight-years-old and can’t see out of both eyes. This is a patient that presented to Dr. Goldstein and I have several patients like that in the past. We fortunately don’t see this anymore. These patients either did not seek, have the appropriate care sought or this was missed. And the patient had really no symptoms other than vision loss, ultimately, when they presented for a school screening exam. Here’s a patient with more chronic disease as well with calcific band keratopathy, posterior synechiae, and chronic inflammation. Again, notice the white, quiet eye. This is a very young patient, this was a 5 year old. Again, bilateral, non-granulomatous, quiet conjunctiva, there’s usually a lot of cell at the anterior chamber, mild amount of flare. Again, the diagnostic procedures we’ve talked about, rheumatology consultation is very important. Already talked about these risk factors. The differential diagnosis for JIA is the same as the differential diagnosis for all of the other chronic anterior uveitis conditions. With one addition that I mentioned for kids and that’s Blau syndrome. Blau syndrome is a familial granulomatosis. It’s akin to sarcoid, if you will, that’s associated with a specific gene mutation in NOD2 region. And this is that nitric oxide case 2 mutation is associated with severe granulomatous inflammatory disease systemically and especially in the eye. Very difficult to treat and usually presents in the first two decades of life with several inflammation in both eyes. There’s usually a family history of granulomatous inflammatory disease in this condition. That’s something to keep in mind of differential diagnosis. The other things we’ve already discussed in the differential. Again we talked about treatment already. Start with topical steroids and mydriatics and add with moderate disease corticosteroid-sparing immunomodulatory therapy. Typically the first line of therapy’s methotrexate in children for JIA. And then the second line of therapy is the addition of a biologic such as infliximab or adalimumab. That has been my typical management for these patients. Calcific band keratopathy complications can be managed by removing the calcific band under anesthesia. This can be done with EDTA chelation. Cataract surgery, well, this is a very controversial topic in very young children. Especially in young children with inflammation. There are two schools of thought. But if the inflammation is very well controlled and the patient has very few structural complication, there’s not a lot of flare in the anterior chamber, then removal of the intraocular lens and placement of an intraocular lens in the bag, in the capsular bag, is still an appropriate approach for the treatment of cataracts in JIA patients. But that’s only with meticulous control of inflammation, well controlled inflammation for many months before cataract surgery and then continued excellent control of inflammation afterwards that will guarantee success. Otherwise if the patient has had a history of poorly controlled inflammation and has not done well and has had really significant structural compilations including glaucoma, et cetera, they’re much better off left aphakic, unfortunately with a lensectomy, vitrectomy approach and that’s still fairly commonly utilized. Sometimes they have in common with glaucoma, requiring tube shunts. Tube shunts are the most effective for children in the control of their intraocular pressures. There are many other complications that we can talk about related to the disease as well. Such as chronic hypotony, amblyopia, cystoid macular edema, all of these are not unique to children except amblyopia. And amblyopia is a significant risk factor and management of amblyopia often complicates the management of the uveitic condition in children. This is something that you have to keep in the back of your mind especially in kids younger than the age of 14. Here’s a calcific band of keratopathy example of a patient. You can see these areas of clearing which represent areas where the corneal nerves are perforating the Bowman’s membrane here. There are JIA-like cases where there’s no arthritis and just uveitis. What’s interesting is that in the management of JIA, the arthritic component becomes not an issue. Because the oligoarticular cases are mild and the medications that we use to treat the chronic inflammation, that’s going to be very effective in controlling the arthritic component of disease as well. These kids are very active, they end up growing and leading normal lives because of the use of immunomodulatory therapy. It’s very different than it was 50 years ago. There’s been great strides made in this. I’m going to skip ahead. We’re coming down to the wire here the last few minutes. I’m going to see if we can, we’ll do this next question and see if we can talk a little bit about len-induced anterior uveitis. This is another identifiable cause of inflammation. What is the main difference between phacoantigenic uveitis and phacolytic uveitis? Phacoantigenic uveitis is most commonly associated with hypermature cataract while phacolytic uveitis is associated with trauma. Phacoantigenic uveitis is treated by cataract surgery, while phacolytic uveitis is treated medically. The two terms are interchangeable. And then the final one is phacoantigenic uveitis is most commonly associated with trauma, while phacolytic uveitis is associated with hypermature cataract. Phacoantigenic versus phacolytic. This is a terminology question. It’s more academic than it is… Let’s see what everybody thought. That’s the last, you guys all got it right, number four. Phacoantigenic means, if you disrupt the lens capsule traumatically or doing a vitrectomy surgery, for example, the patient will develop severe inflammation because of the release of antigens from the lens and that’s called phacoantigenic uveitis. In the case of phacolytic uveitis, you have a hypermature cataract, the nucleus has sunk, the cortex has liquified, and the liquified cortex leaches out of the posterior capsule into the anterior chamber, and large macrophages follow that fibulary lens protein and clog up the trabecular meshwork and result in inflammation. That’s the main difference between the two. The next few slides will just review that. Phacoantigenic usually has a history of trauma, intraocular surgery, sudden insidious onset of decreased vision. Phacolytic is progressive loss of vision due to worsening cataract. And again it can have sudden or insidious onset, usually it’s the immunologic reaction to the lens material. And the difference between the immunologic reaction determines what you call it. If you have a rupture of the lens capsule it’s phacoantigenic, if it’s leakage of lens protein from an intact capsule it’s called phacolytic. That’s really that bottom line. Phacoantigenic uveitis can be granulomatous or nongranulomatous, it can be mild to severe, you can see KPs, they can be mutton fat KPs, you can see synechiae, you can see a hypopyon if it’s really severe inflammation. You can see retained lens material in the anterior chamber from the trauma or from surgery and the elevation of intraocular pressure is quite common. In phacolytic you’ll see large, refractile cells in the aqueous containing, these are macrophages containing this fibrillary lens material lipid. They clog up the trabecular meshwork and result in elevated intraocular pressure. The lens capsule can look wrinkled as the lens becomes hypermature. The testing that you can do to make that, but the history is going to tell you what the problem is and what you need to do about it. These are typically surgical conditions and taken care of with phacoantigenic, just remove the lens material. Typically usually vitrectomy surgery and the cleaning up of the anterior chamber at the same time and removal of any lens material in the eye, and that will take care of the problem. With phacolytic, take the cataract out and washing out the anterior chamber typically resulted in resolution of the problems. Differential diagnosis includes other things that we’ve talked about related to anterior uveitis. But one specific thing to think about is sympathetic ophthalmia, that is in the differential diagnosis. But remember sympathetic ophthalmia is bilateral granulomatous inflammation. Postoperative endophthalmitis in the case of a hypopyon post cataract surgery, you need to think about that in the differential. Here’s the acute inflammatory reaction associated with phacoantigenic uveitis. You can see a lot of PMNs here along with some large macrophages as well and lymphocytes. We already talked about some of this. Really the ultimate treatment is going to be surgical therapy and removal of the lens. So that’s really curative in both of these conditions. Next question. 40-year-old man with Fuchs’ iridocyclitis undergoes cataract surgery. He is at increased risk for which of the following complications? Aqueous misdirection syndrome, inadequate anesthesia from intracameral lidocaine, anterior chamber hemorrhage, or positive posterior pressure? It’s kind of a funny question. So Fuch’s iridocyclitis, that’s our next topic. They have small iris angle vessels that are funny. They are not rubeosis but these angle vessels are fragile and sudden reduction of intraocular pressure can cause a hemorrhage. There’s a name for this, it’s called Amsler’s sign, it was described, I presume, by Marc Asler, the same person who invented the Amsler grid. They can develop hyphema. Which of the following findings most likely in an eye with Fuch’s heterochromic iridocyclitis in the absence of prior surgery? Would you see cystoid macular edema, diffuse KPs, posterior synechiae, or Koeppe nodules? Yeah, exactly. Diffuse KPs is what you see. In Fuchs, you really don’t, even though there’s a lot of inflammation in the anterior chamber, you don’t get posterior synechiae. You typically won’t see nodules on the iris. Although, I will say if you can see Busacca’s nodules in some folks. I think in patients, at least in my practice in the US, I have seen patients who are from India who have an unusual presentation for Fuchs. I have Hispanic patients also who can develop small nodules on the iris for Fuchs. But they have diffuse KPs. they don’t have cystoid macular edema, they don’t have the other anatomic compilations of chronic anterior uveitis. That’s what’s really interesting. We don’t really know what the cause is. We do know based on Debra Goldstein’s work that since the advent of the rubella vaccine, that we’re seeing fewer cases. Likely rubella might be the underlying cause. There are metagenomic sequencing studies that Thuy Doan that’s at UCSF has done to show that rubella may indeed be the underlying cause at least with one case, of Fuchs heterochromic iridocyclitis. Cytomegalovirus and toxoplasmo have also been implicated. Dr. Phan in Hong Kong, she has done some work in looking at the viral causes of anterior chamber inflammation. And a Fuchs type of presentation is not uncommon for patients who have CMV anterior uveitis or cytomegalovirus anterior uveitis. That’s why that’s in the differential diagnosis. Patients usually have heterochromia and have abnormal angle vessels. And there may be some unusual immunoglobulin deposits in iris vessel walls that’s present here. And usually patients have no pain or photophobia. It’s just found on routine examination. You’ll see that the bluer iris will, it’s maybe hard to see in dark irises, but lighter colored irises usually become a little lighter. They’ll lose the definition in the iris crypts. You won’t see transillumination defects typically, unless there’s very, very late stage disease. Typically with transillumination defects you think about herpetic disease, viral diseases like that versus with Fuchs you don’t see that. Usually see a loss of the crypts and the surface architecture of the iris. Here’s a patient who’s got Fuchs, the patient has it on the, you can see the cataract on the right eye on the top right picture. And then here’s the granulomatous KPs. The heterochromia itself should tell you the differential diagnosis of heterochromia includes congenital Horner’s syndrome, also could be associated with heterochromia if you can remember. And then if they have unilateral use of prostaglandin analogues can cause some heterochromia as well and lash growth, that can tell you in glaucoma patients. Again, these small, stellate KPs are quite characteristic, they’re distributed throughout the cornea. There’s iris atrophy. Again, involving anterior iris stroma loss of crypts. Again you don’t see transillumination defects. And there might be a few Koeppe’s nodules but more commonly in pigmented patients I’ve seen some Busacca’s nodules. Anterior chamber cell and flare. Usually there’s no posterior synechiae complications with this although you can see vitritis and vitreous opacities are not uncommon. Cataract occurs in a significant portion of patients and up to 50% can develop glaucoma. The abnormal angle vessels are not rubeosis, they don’t need to be treated with PRP or anti-VEGF therapy. They don’t cause angle closure. They can be associated with anterior chamber hemorrhage if they’re in cataract surgery. The differential diagnosis includes herpetic uveitis, including CMV anterior uveitis which I alluded to earlier. Sarcoid uveitis can present in many different ways. Like I said, congenital Horner syndrome, iridocorneal endothelial syndrome can cause unusual appearances to the iris. Diffuse iris melanoma can cause heterochromia. I told you about prostaglandin analogue therapy. And, of course, syphilis is a differential of any anterior uveitis. I typically try to minimize the use of corticosteroids on these patients. Some patients may have a little pain or discomfort. They can use a steroid periodically for that, but not chronically. Because the chronic steroid use just increases the risk of them developing cataracts quicker and developing glaucoma more quickly so I try to avoid that in these cases. If we think it’s cytomegalovirus is the cause of this Fuchs-like picture, then you can try Ganciclovir for treatment. This has been meant with maybe minimal or limited success. Not in my hands, anyway, and again Ganciclovir systemically is quite toxic to give. You have to be really careful how bad things are and how much you want to try to treat this patient for the inflammation. Cataract surgery’s standard. You don’t have to really do any kind of preoperative treatment. You don’t have to do anything to get the patient ready for the cataract surgery. Unlike a patient with JIA where you have to really have the patient very quiet for many months before and can really do exercise meticulous control and even pulse steroids before the surgery, right around the time of surgery and gradually taper. You’re not having to do that with Fuchs patients. And the glaucoma can be very difficult to treat. Vitreous opacities are visually significant. In some cases you can treat with vitrectomy surgery but I have avoided doing that. I have had patients develop anterior segment hemorrhage that goes into the posterior segment after vitreous surgery. Non clearing, resulting in worsening glaucoma and losing vision in one patient, so I’ve decided in the future to avoid vitrectomy surgery if I can. I’ll quickly touch on viral anterior uveitis, specifically herpetic anterior uveitis with a quick question. I have just a couple of minutes here and I’m sorry I’m going to try to finish this up as quickly as I can. Which feature is most consistent with the uveitis secondary to herpes simplex? Number 1, bilateral uveitis? Number 2, diffuse KPs? Number 3, vitritis without retinitis? Number 4, prompt response to topical trifluridine? Viral herpetic anterior uveitis. Diffuse KP is the best answer, that’s right. Usually it’s unilateral disease. You rarely will see vitritis without retinitis, that would be a very unusual thing. And usually doesn’t respond to topical. Anterior segment inflammation like this doesn’t, that’s herpetic, usually requires systemic antiviral therapy. So diffuse KP is the best answer. Etiology, it can be HSV, VZV, or cytomegalovirus. The confirmation is going to be by aqueous PCR. And this is crucial in modern uveitis management, doing an anterior chamber paracentesis and having it sent to the lab to evaluate a 0.1 milliliter sample for HSV 1 and 2, varicella-zoster virus, and cytomegalovirus is important when you’re considering herpetic disease in the differential diagnosis. HSV can be recurrent or chronic, usually unilateral. Almost always unilateral, it’s very rarely bilateral. And there may be some history of corneal herpetic disease, there may be oral or genital cold sores that potentially give you a clue as well. Varicella-zoster virus usually will have a history of ipsilateral herpes zoster skin lesions. Usually we’re talking about ophthalmic zoster. It’s going to involve the distribution of cranial nerve five division one, involving the nasociliary branch with Hutchinson’s signs and lesions on the tip of the nose with zoster. You can sometimes see zoster sine herpeticum associated with uveitis but that’s pretty rare. Patients usually will have some pain and redness and foreign body sensation. There may be some corneal epithelial disease. But there may be stromal disease, stromal edema may be present, there may be endotheliitis. And the endotheliitis may be localized to where there’s stromal edema and disciform keratitis. There may be KPs just in the area where the stroma is edematous and localized not diffusely in those cases. There can be just isolated anterior chamber inflammation alone with no corneal signs at all and corneal edema and elevated intraocular pressure caused by endotheliitis that affects the endothelium as well as the trabecular meshwork. KPs can be variable but usually they’re small and stellate. If you don’t have disciform keratitis with just anterior uveitis you’ll have pretty diffused KPs. There may be some subtle corneal scarring or haze which is best seen with sclerotic scatter. Even in the absence of disciform keratitis with HSV. Pressure will be elevated and that’s one of the key signs of presentation. And there will be stromal iris atrophy. The presence of iris atrophy or stromal, sectoral, or diffuse iris atrophy is not you can’t say that that’s zoster or simplex just by looking at that. Because both can cause iris atrophy. The only way you can determine which virus is to do PCR testing. Serologic testing for these viruses is pretty useless until the serologic test is negative. Only PCR testing is definitive. Hypopyon typically doesn’t happen. Sometimes we can see hyphema combined with inflammatory so there may be combined inflammation and blood in the eye with herpetic anterior uveitis. Zoster, similar kind of presentation, similar appearance clinically as well in the eye. And similar ocular issues. And again they may not have any corneal disease at all. With cytomegalovirus, there may be two types of presentation. One is acute, pain, redness, photophobia, and elevated intraocular pressure like what we used to call Posner-Schlossman syndrome, which is probably acute CMV anterior uveitis. And then there’s the more chronic one that is asymptomatic and looks like Fuchs that may occur. Both can be associated with elevated intraocular pressure, diffuse KPs, iris atrophy, et cetera. Again, the diagnosis is based on PCR testing. This is really key, serology is rarely helpful unless the antibody is negative and it excluded the diagnosis then. We already touched on this. But there are risk factors, presence of atopic disease is a risk factor for herpetic disease. And prior HSV infection in the lip or genital infection can be a risk factor. And with varicella-zoster, advanced age, immunosuppression, and atopic disease also is a risk factor. The differential diagnosis, we’ve already touched on includes almost everything that you can include with anterior uveitis. But specifically because it’s unilateral, you include Fuchs, the likelihood or possibly Posner-Schlossman syndrome, that sort of thing in the differential diagnosis. The treatment is usually oral, you treat the epithelial keratitis with topical antivirals but systemic antivirals are highly effective for both the epithelial disease as well as the intraocular inflammation. And once the cornea is healed, you can use topical corticosteroids. And the corticosteroids should always be given with antiviral coverage in these cases. If you don’t have any corneal disease at all, use topical steroids, cycloplegics, and systemic antivirals is the treatment for both zoster and for herpes simplex virus. I tend to maintain patients with chronic disease on antiviral therapy maintenance for sometimes many years because the disease can be very persistent. CMV anterior uveitis is a much more difficult thing to treat. I alluded to this earlier. Oral Ganciclovir in conjunction with sometimes topical Ganciclovir as well. But topical steroids are also utilized in the treatment of this condition. And this is much more difficult because it’s more chronic. You can see iris atrophy, dilated pupil, post-herpetic neuralgia, there are all potential complications, cataracts, glaucoma, hypotony can also occur. And here’s a picture of a patient with zoster that developed this diffuse iris atrophy. This patient was also HIV positive.Patient was treated with aggressive antiviral therapy and maintenance antiviral therapy along with topical steroids. I think that’s the end of my talk. Let’s see what questions I can answer. I know this is, it’s kind of a funny talk. I didn’t know how to organize this well. This is the first time I’ve tried this approach and I appreciate all of your attention. But really the talk was focused on anterior segment disease. I want you to take away that acute anterior uveitis presentation, especially with hypopyon, you need to think about HLA-B27. Bilateral chronic anterior uveitis in children, think about JIA. Don’t miss that diagnosis. Make sure that they’re referred and taken care of appropriately. And treated aggressively with immunosuppressive therapy to prevent complications and blindness. And then bilateral acute anterior inflammation in patients in their first two to three decades of life, think about tubulointerstitial nephritis and uveitis syndrome. And then unilateral anterior segment inflammation with elevated intraocular pressure, think about herpetic disease. If you take away those four points, I think that that’s very important. And then remember in the laboratory work up of a patient, that the only time that you want to think about getting an antinuclear antibody or rheumatoid factor for an anterior uveitis work up is in a child when you’re concerned about whether or not they have JIA and what type of JIA they have. And then finally, remember that all uveitis patients need to be checked for sarcoidosis, syphilis and tuberculosis as part of their laboratory work up. And based in the remainder of the lab work up will be based on their clinical history and their physical examination findings. I have just a few minutes I’ll try to cover. Let me see if I can answer the questions. First question, if the small, subtle hypopyon in the AC, is it grade as four plus? Probably. And I think that that’s reasonable. If you look at the size of the hypopyon is not part of the grading system, but the presence of it is. It just means that the inflammation is severe enough that it congeals into that hypopyon in the anterior portion of the anterior chamber. Are there, let’s see here. In the case of acute hypopyon anterior uveitis, what differential diagnosis must you consider? If it’s an acute unilateral anterior uveitis hypopyon, HLA-B27 is, as I said, top of the list of things. I would check two things on that patient. Syphilis serologic testing and check for HLA-B27 in a patient who present with acute hypopyon. How do you differentiate TB and sarcoid clinically? You can’t. But I think that idea behind TB and sarcoid in terms of the eye, clinical history is going to tell you more than a clinical examination of the eye. If the patient has had significant weight loss, night sweats, fevers, other things and you’re in a TB endemic area, well, it’s going to be TB. You have to rule that out first. And if the QuantiFERON assay, the IGRA, the Interferon Gamma Release Assays or the skin testing, and the check x-ray suggests TB, then obviously treat for TB. The other way is, of course, diagnosing it by tissue biopsy and bronchoscopy, and/or mediastinoscopy and tissue biopsy. Conjunctival biopsy if you see specific conjunctiva nodules that suggest sarcoid can be very helpful as well. Are there different severities of anterior uveitis in HLA-B27 if positive or negative? Remember that 5-8% of the population is HLA-B27 positive. If you check people randomly, you’re going to get 5-8% positive. That’s not going to tell you anything. It won’t help you. It won’t help you manage the patient. But if the patient says, “I have low back pain.” And they present with one eye with hypopyon uveitis, and this is the third episode they’ve had in five years, that HLA-B27 is related to his back pain and his uveitis. You understand what I’m saying? Lab testing is only useful if it makes sense in the clinical setting. And yeah, you can get a hypopyon and not have B27 positivity and have idiopathic anterior uveitis, it’s less common, but yeah, you can still get it. Is it required to investigate a first episode of several unilateral anterior uveitis? If they have a hypopyon I would. I’d get an FTA or anti-treponemal IgG and HLA-B27. Is oral steroids needed in case of anterior uveitis spillover anterior vitritis? Typically not if you take care of the anterior uveitis well, it should get better. But if the patient complains of a lot of floaters and you see that the vitreous cells are extending more posteriorly, then you may need to use more aggressive therapy. Topical difluprednate has good penetration even into the anterior vitreous. It might be helpful acutely, it’s not great chronically. In case of VCZ anterior uveitis on AC tap, and IOP was raised, what is the advice on zoster vaccination? That is a loaded question. I don’t know the answer to that. I suspect that that means that that patient may develop immunologic response and develop inflammation after zoster. This is a very smart guy who’s asking me this question. I don’t…other people have asked me that question. I have not received my zoster vaccine. I had chicken pox in India when I was growing up, but I have not received my zoster vaccine. But I suspect that there’s more value in avoiding zoster and getting zoster. So I would say probably you should get it. But I don’t know what that would do to the eye. I don’t think that we have that answer. Do you consider HSV anterior uveitis in a case of normal periorbital skin and normal cornea? Only if you see diffuse KPs, elevated intraocular pressure, and acute anterior uveitis at presentation. That’s in the differential diagnosis. And then you can tap and do the PCR. Do you add phenylephrine along with cycloplegic eye drops that patient use at home in the first week in severe cases? In severe cases I usually use atropine. Phenylephrine doesn’t do much because as a cycloplegic agent it only lasts for about 20 minutes or so and it’s not really cycloplegic, it just is a dilator but you can still see constriction of the pupil. I would use cycloplegics such as homatropine, atropine, for really severe cases. And then for milder cases cyclopentolate is useful, 1% or 2%. Do you recommend lab tests in the first attract of anterior uveitis without any systemic findings? Any uveitis is really an abnormal finding. The philosophy now is that if you suspect systemically based on review of systems that something is going on, get testing. Do testing. But do focused based on what you find clinically and your history. What medications do you recommend to break posterior synechiae? Acutely, I’ve used atropine chronically, but in the office I use a pledget, a cotton pledget or a Q-tip soaked with a lot of drops. And I use a topical anesthetic and then just put the pledget very gently at the limbus where the synechiae are. That can be utilized to break posterior synechiae if they’re really severe. I douse it with Cyclogyl, Mydriacyl. Cyclopentolate and Mydriacyl, or tropicamide, and then Neosynephrine drops all together, and then just put it very gently at the limbus if the patient will allow you to do that after topical anesthesia. Which do you prefer as last choice of treatment of high IOPs? Alphagan or prostaglandin analogues? You can use any medications for the treatment of uveitic glaucoma. You can use any of them. But I do agree that prostaglandins do tend to be pro inflammatory. I would rather use carbonic anhydrase inhibitors and/or alphagan and beta blockers first typically before I go to prostaglandins. And the newer agents like nutarnucil, those are even more, they’re very, they make the eye red. I just don’t. And I use them, we have to because nothing else works and often the patient will be on some anti-inflammatory coverage topically anyway. I think you have to use what you have to use. We have a nine-year-old boy with a history of pencil penetrating injury to his right eye a month ago, a cornea TNS with lens extraction and IOL implant. Post surgery severe inflammation, fibrin, high IOP, so IOL was removed and partial anterior vitrectomy, intravitreal antibiotics. Now post one month still has severe inflammation ongoing fibrin in the AC and shallow anterior chamber. Given oral methotrexate low dose. If the other eye is normal, I still suspect that there may be some retained foreign body. It still sounds like there’s infection. These are really tough cases. A pencil in the eye is a wood foreign body, I would worry about fungal endophthalmitis. COVID uveitis. No comment. (laughs) I think COVID has been associated with increases in cases of uveitis. How about the use of oral steroids for positive syphilis testing before penicillin is given? No. Don’t use anything systemically that would make things worse. Get the test back. Use topical steroids until you know that it’s not infectious and then you can use more aggressive treatment. So definitely not. Must I order UBM in all cases of idiopathic anterior uveitis to angle mass. No, do a gonioscopy, look for angle mass, you don’t have to do UBM. If you’re thinking something like that. Do a gonioscopy, do just a regular ultrasound, you don’t need to do a UBM unless there’s something in the history that tips you off. You don’t do it, I don’t do it on everybody. How long do you wait before cataract surgery in case of anterior uveitis? Three months of quiescence minimum, on or off medical therapy, doesn’t matter. Three months of quiescence without any cell in the anterior chamber, minimum, before you can do surgery. One week prior to surgery, increase the drops to every hour. Add oral prednisone if possible a week before surgery at 40 milligrams daily. Gradually taper about 4-6 weeks after surgery. And meticulous control before and after surgery. With chronic anterior uveitis it’s even more paramount for meticulous control before and after. If chest x-ray is clear in chronic anterior uveitis and positive QuantiFERON, history of old contact with TB, would you start an anti-TB therapy? Infectious disease will usually request more evidence of active disease. You have to decide. If it’s just anterior uveitis and nothing else, you probably don’t need to do that. But on the other hand, if the patient has Ghon’s complex, has other things going on, then it’s obvious that they need to be treated for latent TB. This is a very controversial area. I think if you read there is a COTS study that Rupesh Agrawal, one of my good friends, he’s a really fantastic guy. He may even be on this call, he may be one of your attendings. He’s written multiple COTS recommendations. You may read that, that’s actually an international publication that’s available. So I would refer you to that journal. How do you treat high IOPs with active uveitis? Treat the uveitis first, add a topical beta blocker. The treatment of the uveitis is very, very important. Some tips of preventing a recurrent or reducing Posner-Schlossman syndrome recurrences? (laughs) If I knew. I think one possibility is that Dr. Chi is working on, Soonfek Chi is working on is using the Ganciclovir to see if that will help. I don’t know what her results are to date. But I think it can be difficult. But topical maintenance corticosteroids may be a very, very shallow low doses may be useful. I don’t know. How to follow children with JIA? I gave you a big slide set of all of the different categories. The most important thing to remember is those who are between under six years of age who have pauciarticular disease and ANA positive and girls, they need to be checked every three months until they reach the age of at least seven. And they go to every six months if they develop inflammation. What is the progress of JIA, does it continue to adult? Yes. There is a lot of new evidence to suggest that with the use of biologics that we don’t make the disease completely burnt out, the disease continues to progress and become a problem. Not progress, but stays active and stays an issue from a monocular standpoint for patients even if the systemic disease goes away. When anterior uveitis with macular disc edema, this indication for systemic steroids may be edema resolve with only intensive steroids or when? Disc edema usually can be associated with anterior uveitis, especially in children. And the disc edema does get better with the treatment of the inflammation, in my experience. Do I need to do ACPCR in every Fuch dystrophy? No, if it’s long-standing Fuchs I wouldn’t do it. Do you recommend specific antiviral drug for Fuchs? No. Not unless you prove again that the PCR is CMV positive. And then in case of unilateral panuveitis, old patient, differential diagnosis? Well, that’ll take an hour of lecture. (laughs) I’m sorry, I’m not trying to be facetious. I’m going to cut off the questions here because of COVID-related uveitis. COVID is a revolving issue. I will tell you that COVID, I’ve seen patients have HLA-B27, patients flare after COVID vaccine and after having COVID. I’ve also seen patients have no change in what I’m managing, I’m not seeing any increase in incidents of COVID uveitis. TINU has increased in frequency in COVID, I think. And so has acute macular neuroretinopathy. Thank you for your attendance and your interest. I have to go to surgery, that’s why I’m in a little bit of a hurry. I’m sorry. And I really appreciate all of you, it’s a real honor to speak to you all. I hope you learned a few things. I know I learned a lot from you guys always. Take care.