 Hi, my name is Marissa La Rochelle and I am UVitis faculty at the Moran Eye Center in Salt Lake City, Utah, University of Utah. And today we're gonna be doing a lecture which I've titled, Anterior and Intermediate UVitis, A Practical Approach for the Comprehensive Eye Provider. This is a lecture I've given to several groups of optometrists and comprehensive ophthalmologists. And I thought I'd record it so we can share it on the Moran core. All right, so over the next hour, we'll go through a quick review of definitions and then this is gonna be a case-based lecture. So we're gonna go through six cases and then I'll highlight some important points of each case. The learning objectives are as follows. And to start, this is the sun which stands for standardization of UVitis nomenclature, working group classification. So this is how we talk about UVitis and this working group, it's a bunch of people that sit around and they talk about how we should distinguish UVitis, which is very helpful. So UVitis is named on the primary site of inflammation, the anatomical location of where that inflammation is. So as you can see from this chart, anterior UVitis is when the predominant site of inflammation is in the anterior chamber, that's the space between the iris and the cornea. And this includes entities like eritis, erotocyclitis, whereas intermediate UVitis is when most of the inflammation is in the vitreous chamber, including parsplanitis when intermediate UVitis is idiopathic. And then posterior UVitis requires an inflammatory lesion in the retina or the corroid, things like multifocal coriditis, birdshot would fit into this category. And then pan-UVIitis is when you have all of the above. So you see inflammation in the anterior segment in the vitreous as well as posterior involvement, meaning an inflammatory lesion in the retina or corroid. Importantly, just macular edema or optic nerve edema does not count as posterior involvement. Those can just be secondary to anterior intermediate UVitis. So for grading inflammation, this is very useful because it lends some consistency between observers, between clinicians. And that's important for following patients in clinic as well as for research purposes. So when we talk about anterior chamber inflammation, we're actually counting the number of cells that we can see in a one by one millimeter beam of light at the solit lamp. And if there's about 10 cells in that area, that's one plus, about 20 cells is two plus, 30 cells is three plus. Once we're at the 20, 30, 40 range, we're not counting individuals to cells, but we're still using that as a grade. And then for the way we grade flare the way we grade flare is the haziness of the details of the iris and the lens, as you can see here. All right, now for grading vitreous inflammation, rather than counting cells, vitreous haze is based on how easy it is to make out the features in the posterior segment. So we can see a score zero. There's well-defined margins of the disc. We can easily see the vessels. And when we get to two and three plus, we're losing some of the definition of the optic nerve and four plus vitreous cell, we can no longer see the optic disc. Okay, onto our first case. This is a seven-year-old man with unilateral eye pain and redness. It happened all of a sudden, so it's acute. He's also experiencing light sensitivity, otherwise healthy, visual acuity and effective eye, affected eyes decreased at 2060. And we can see some asymmetry of his intracular pressures with the affected eye being higher. This is an anterior segment photo, and it's notable for some scleral or contantival injection, some corneal haze, and it looks like there's some pigment on the endothelium. It's hard to grade anterior chamber cell with this photo, but we can clearly see that the eye is red and there's corneal involvement. His slit-lamp exam is notable for injection. He has both small and medium KP, urecuratic precipitates, as well as pigment on the endothelium with decimative membrane folds, that's DMF and corneal edema. Anterior chamber has inflammation, two-plus cell and flare, and we also notice some transillumination defects in the left eye of his eras. So differential diagnosis for this patient would be idiopathic, meaning, iridescent happen, we're not sure the cause of it. Herpetic is definitely suspicious with that high pressure on the left side. HLA-B27 definitely presents as an acute unilateral anterior uveitis, and then always think about post-surgicals, that would be infectious endoplamitis. Patient had cataract surgery a week ago, and then traumatic. So I'd ask about, does this patient have prior cold sores? Any recent surgeries? And then you step back from the slit-lamp and you look at the entire patient and you notice he has a zoster rash in the V1 distribution. So I think that's a slam-dunk diagnosis for herpes zoster-associated anterior uveitis. I would call this a keratou uveitis since there's inflammation both of the cornea and anterior chamber. Classic findings of herpetic uveitis, high intraocular pressure. So usually the intraocular pressure in patients with iridus is low due to ciliary body shutdown from inflammation, but in herpetic disease, due to a trabeculitis, the IOP is paradoxically high, higher than normal. Corneal involvement, so we all know a dendrite or pseudo-dendrite tips us off easily to herpetic disease, but really any corneal involvement. It can be stromal edema, desiname membrane folds, focal endothelial disturbances or opacities. Decreased corneal and safe sensation, if you remember, maybe on the next visit to check the corneal sensation before your technician puts in the properacane. Recurrent iridus only in one eye. So B27 disease, which is on the differential, but it typically will alternate eyes over course of years if you have a patient that's always in the same eye, consider herpes. Sorry, I skipped over iris atrophy. So the classic teaching is that HSV causes patchy iris atrophy and that VZV causes sectoral atrophy, but this isn't always the case. So any transillumination defects think of herpetic disease. And then the KP's, keratic precipitates, they really can vary in size, shape, location. They can be mutton fat, greasy. They can be small and fine, distributed anywhere on the cornea. So for laboratory workup in this patient, he comes in with that classic vesicular rash and V1 distribution. I probably wouldn't do any other workup for uveitis since that's a pretty clear diagnosis. The caveat being, if it's a young patient, a 25-year-old, and he comes in with that zoster rash, I would probably check a HIV since normally young immunocompetent patients don't get zoster. You must dilate this patient. So although it would be atypical for an immunocompetent patient to start with shingles and iritis and then progress to posterior involvement with the retina or acute retinal necrosis, you must check. So definitely dilate the patient at the first visit. And then on subsequent exams, it's okay to just follow the anterior chamber flare with non-dilated exams unless the vision drops and the vision doesn't seem in proportion to what your anterior segment exam findings are. Then dilate again. Okay, management for herpes zoster. Val tracts is val acyclovir one gram three times a day for seven to 10 days. Acyclovir is less expensive and the dose is five times daily. Instead of just abruptly stopping the antivirals, if they're on long-term topical prednisolone, sometimes I just reduce the dose of the antivirals to a prophylactic dose, such as 500 or one gram of val tracts daily for as long as around the topical steroids. I would use topical steroids based on the degree of anterior chamber inflammation and corneal edema. However, if there's epithelial involvement, such as a dendrite or pseudo dendrite, sometimes I hold off on that topical steroids for a couple of days, make sure that the epithelium's healing with the antivirals and then a couple of days later, add the topical steroids. You can also consider using Ganscyclovir topical. Okay, so this is a clinical pearl from Dr. Vitale, Dr. Foster's book that states, it is widely believed that uvitis associated with involvement of any corneal layer is a manifestation of herpetic disease until proven otherwise. Some patients need what I call long-term, low-dose antivirals and possible topical steroids. So if they continually recur with herpetic disease, I may have them on one drop a day of prednisolone acetate or 500 milligrams, Valtrex daily to just suppress their inflammation. Importantly, if you're managing patients for cataract surgery and for any other kind of retinal surgery, I tend to increase the oral antivirals around the time of operation because we know surgery can reactivate herpetic disease. So I'd go back up to treatment dose on the oral antivirals, maybe starting a week before surgery and then continuing it for a couple of weeks after surgery. Dialyte every patient with uvitis. All right, our second case. We have a 25-year-old woman. She comes in with redness, pain, light sensitivity. This is three days after being hit in the eye with a soccer ball. Past medical history for systemic lupus. She wears contact lenses, vision slightly affected in that right eye, pressures are normal, and you do notice that the right pupil isn't reacting properly. Her anterior segment exam is notable in the right eye for mild anterior chamber inflammation, a few karate precipitates. So what's her differential diagnosis? She said she was hit with a soccer ball about three days ago. This could be definitely traumatic. Iridis would be top of the differential. Other things to think about are those actually red blood cells or pigment? Is this a traumatic microhythema? Of course, look for other signs of trauma, corneal abrasions, iris involvement, less likely in a cold, open globe or retained foreign body with that good vision. And then think of unrelated inflammatory iridis, and it's possible that that injury was just a red herring. I'm sure we've all had patients that relate something like getting dust in their eye to something that couldn't possibly be related, like bilateral age-related cataracts, but it's just that that event brought attention to their eyes or their vision. So for a workup in this patient with a history of soccer ball injury to the eye three days prior, I would probably just do a thorough exam. I would dilate the patient, make sure we're not missing anything in the posterior segment, such as commotion or a choroidal rupture, and then doing gonioscopy on subsequent exams in case there's any damage to the angle. So classic findings for traumatic iridis, it's due to blunt trauma, typically two to seven days after the injury, vision is good unless there's other damage to the eye, and then we treat with cyclopegia and topical steroids, and I'd follow within a week. Clinical purse for this one is looking for any other ocular damage, the timing. So if they said they were hit in the eye a month ago and only developed symptoms yesterday, probably not from the trauma. Okay, so I put lupus as part of her past medical history, sort of as another red herring. Patients with systemic lupus really don't get isolated anterior uveitis as part of their systemic lupus disease. So I think a lot of people think, oh, lupus, they must have iridis or iridis, let's check for lupus. And in reality, patients with lupus just don't get isolated iridis. They can get posterior findings, they can get scleritis, they can get vascularitis, but just anterior uveitis would be very uncommon. Dilate every patient with uveitis. Okay, this is our next case. So in this picture, we can see an anterior segment photo of the left eye, and we see this layering of presumably white blood cells, so much that it's creating a white line at the bottom of the anterior chamber, known as a hypopian. Now let's take a moment to think about a differential diagnosis for this finding. This is how we prepare, how I prepare the residents for oral boards is you just describe a photo and then name something in the photo like a hypopian and then state a differential diagnosis for that finding. So with no other history, if we don't know the patient's age or past medical history, what would be a broad differential for a hypopian? Okay, HLEB27 anterior uveitis, we encounter this commonly in our clinic. What else? Bichette's disease in some parts of the world, bichette's is the most common cause of a hypopian. Must remember infectious causes of a hypopian. So infectious and alfomitis, whether it be post-surgical, such as after cataract surgery, or endogenous can happen in patients with history of IV drug use or sepsis. Infectious, hypopians can occur in association with the corneal ulcer. Drug related, the classic ones that you're tested on is rifabutin that is a medication that is used to treat or used for prophylaxis and the treatment of mycobacterium avian complex or MAC in HIV positive patients. A pseudo-hypopian. So we said that that layering was of white blood cells. Maybe they're not actually white blood cells, but they could be malignant cells. They could be ghost cells and causing ghost cell glaucoma or lens induced glaucoma or steroids. Maybe someone was trying to do a subtenance kennelog injection and accidentally injected inside the eye and then the steroids can precipitate out and look like a hypopian. So take a good history. This is a 30 year old man, so he's young. He said, oh, I had something very similar happen to me. It was the other eye and it happened two years ago. He said no recent surgery or trauma, but he does endorse low back pain worse in the mornings. And when you take a careful family history, it reveals that he had an uncle that walked with a cane and was kind of hunched over at an early age. He had a non-contributory social history. So now this is very suspicious for HLA-V27 related disease. Vision is affected 2100 in the left eye. You can't see to the back of the eye. So you do an ultrasound, but the ultrasound is normal with no vitritus. So what's the workup for uveitis? In general, you can see the workup listed is ruling out things like sarcoid, TB, syphilis. In a patient that comes in with just unilateral, acute, non-granuline, this anterior uveitis, I would just check an HLA-V27 and an FTA, RPR. And this patient was positive for HLA-V27. So I use those words, acute, unilateral, alternating, recurrent anterior uveitis. And those are sort of buzz words to let us know the typical course of this disease, which is very classic for V27 disease. Don't forget that not all HLA-V27 disease is ankylosing spondylitis. We also have to remember psoriatic arthritis, reactive arthritis, and the GI illnesses, like Crohn's or ulcerative colitis, and they can be associated with uveitis as well. About 25% of all men with any type of anterior uveitis end up having ankylosing spondylitis. And then if we only include patients with unilateral, acute anterior uveitis, it'll be B27-related in over 50% of the time, as high as 81% of the time. Okay, management for that HLA-V27 associated anterior uveitis, topical steroids, encyclopedia. So topical steroids, how much is enough? I use this one to four rule, which I kind of just made up. This is a rough guideline. It's not in the literature, but the one to four rule is one plus AC cells. So that would be about 10 to 15 cells for high power field equals four drops of prednisolone acetate, 1%. So then double it. If you have two plus AC cell, that would mean eight times a day, prednisolone. Once we're up to three and four plus AC cell, then we're talking about hourly prednisolone acetate. And this applies for prednisolone acetate, 1%. Di-flu prednolone or durazole is stronger. So it's about twice as potent. So you could use this rule, but then divide by two accordingly if you're using durazole. It tends to be more expensive, but it can help with the dosing schedule. If you're using it frequently, it can help with the compliance. I do think durazole elevates the pressure more frequently, especially in children. So that's something to watch out for. With patients with severe anterior segment inflammation that you know is not infectious, you can consider a short course of oral steroids or sub-teen-ounce catalog. And then prevention. I have a question mark near oral NSAIDs. So there's pretty good evidence that long-term oral NSAIDs, such as naproxen, taken regularly can prevent the recurrence or suppress the inflammation and decrease the episodes of anterior uveitis and B27 disease. But I tend not to use chronic oral NSAIDs to prevent episodes of uveitis since there's some concerning side effects that have come out more recently. In addition to the known GI upset and kidney-related complications, a question mark of cardiovascular disease with chronic oral NSAIDs. So I would rather treat the episodes which are intermittent, acute, tend to respond to the topical steroids or a very short course of prednisone rather than having patients on long-term oral NSAIDs. If a patient is on immunosuppression like Methotrexate or Humira for their joint disease like Inculos and Spondylitis, this will reduce the number of uveitis flares that they experience. I think a common misconception is that we use immunomodulatory therapy to treat the uveitis in B27 patients, and that's rarely the case. The typical course of iritis in this disease is an acute symptomatic episode with long periods of quiescence and then a recurrence. And so we just treat each individual episode. Clinical pearls, don't forget infectious causes of a hypopian. There is such a thing as too much or too little steroids. I tend to start strong and then taper slowly, dilate every patient with uveitis. Hey, this is case four. We have a 35-year-old man. He presents for a routine exam, no ocular complaints, no past medical history or ocular history. Vision in the left eye is slightly worse at 2025 and he has slightly increased pressure in the left eye, 24. This is a photo of an anterior segment in the bottom right-hand quarter. We can notice heterochromia. So he has different eye color. And then we can see keratic precipitates in the cornea and they look small, white, and they're diffusely located. So from the top down to the bottom of the cornea. So I would call those stellate KP. He has one plus anterior chamber cell and you notice the iris atrophy. This is a little bit of a moth-eaten appearance. He has a mild cataract in that left eye as well and some trace anterior vitreous cell inflammation. You think to do gonioscopy. The right eye is normal, but you notice some fine blood vessels traversing the trapezoid mesh work in that left angle. So differential diagnosis. Top of the list would be Fuchs heterochromic erasiclitis. Always consider herpetic disease with the asymmetric pressures. Posner-Schloßmann syndrome, if that exists. And then other causes of heterochromia, just to keep in mind. Congenital horners, melanosis, melanoma, and then extensive rubiosis can also give the appearance of having different iris colors. So this is pretty classic presentation of Fuchs heterochromic erasiclitis, abbreviated FHI. And you can see the common findings here. This does not have the classic findings of anterior uveitis. So the no pain, redness, light sensitivity. It's classically noted to have this small diffuse paratic precipitates and diffuse, meaning floor to ceiling, rather than just being located in the inferior third of the cornea or ults triangle. Low grade anterior chamber inflammation. So if you're seeing three plus AC cell, this is not Fuchs. The iris stromal atrophy, which is what causes the difference in the eye color. They don't have the classic findings of anterior uveitis. The structural complications like macular dima or posterior snaky eye. And then they can have the fine blood vessels on the surface of the angle. These can spontaneously bleed, causing a high femur, or that can happen during gonioscopy or during surgery. That's known as amsler sign. And then sometimes we forget that there can also be a little bit of anterior vitreous inflammation with Fuchs, as well as the unilateral cataract. These patients often present with chronic open-angle glaucoma that they didn't know they have. So treatment in this is a little bit different. This may be the only case of anterior chamber inflammation that we don't need to treat until there's zero cells in the anterior chamber. So the low grade inflammation is not very responsive to topical steroids. And it's okay to leave the mild low grade inflammation there since it's not associated with the structural complications of anterior uveitis that we see in other disease. Sometimes patients have bouts of increased inflammation that can be symptomatic with pain or floaters. And then we would use a very short course of topical steroids just to treat that increase in inflammation if it was symptomatic. The most important part of Fuchs heterochromic eridocyclitis is to treat the intracular pressure. So these patients commonly developed glaucoma. So really treating the IOP is important. We can get a little bit caught up in trying to treat that AC cell. And now we're putting steroids on the eye and it can be difficult to tell if it's a steroid response versus high pressure from that open-angle glaucoma. Clinical pearls, you see someone with unilateral uveitis and high intracular pressure. I would still think about herpetic disease and don't over treat with steroids. The reasons that we mentioned. Our next case is a six-year-old girl. She comes in your office because she failed vision screening at school and then the parents took her to an optometrist at Walmart and they couldn't refract her to better than 2040 and 2060. So now she ends up in your office. Past medical history is unremarkable but mom does mention that she has a little bit of knee swelling and ankle swelling at times. She has poor dilation and irregular pupils but a normal pressure in both eyes. And then a slit-lamp exam is notable for non-granulomatous KPs in both eyes and to your chamber inflammation. She has posterior sonica bilateral and some posterior subcapsular cataracts forming. Look in the back of the eye and notice that the optic nerves are mildly hyperemic, slightly elevated, but otherwise the fundus looks normal. Doing a MAC OCT, we can see macular edema. So differential for this. High on the list would be JIA-associated uveitis. It's a child that presents with chronic anterior uveitis and has some knee swelling and ankle swelling. Other things on the differential would be idiopathic uveitis that can look much like JIA-associated uveitis but there's no systemic disease. And then TINU, which stands for tubular interstitial nephritis and uveitis is a rare syndrome that involves inflammation of the kidneys as well as uveitis. So work up for this is a little bit different than the work up in adults. I would add a beta-2 microglobulin in the urine that would rule out TINU if it's normal. I checked a rheumatoid factor in ANA in children with anterior uveitis but not adults because that can help you categorize the type of JIA if they end up having it and then ruling out things such as sarcoids, syphilis, and TB. And we talked about the ANA not being included in the work up of adults with anterior uveitis since just anterior uveitis is not associated with lubus. So this is a case of JIA-associated uveitis. Patient was ANA positive. Classic findings of this is the absence of pain, redness, and photophobia. So these kids present with chronic inflammation. They already have structural complications such as posterior synechiae and cataracts because they're not having the pain and redness and young kids aren't able to say that, hey, I have blurry vision in one eye. And then it tends to be non-granulomines, bilateral, anterior uveitis, but they can have some intermediate uveitis as well. Treatment for this. First off, are you confident with the exam that you got in the office? Does the visual acuity fit what you're seeing? If not, then consider an exam under anesthesia. I would start with topical steroids and psychoplegia even before the laboratory work up comes back. And then I would refer these patients to pediatric rheumatology for an evaluation of their joints and they can also help manage immunosuppression. We know that early initiation of immunomodulatory therapy in these patients can be helpful and have better predictors of long-term visual outcomes. In this patient that already presents the structural complications with cataracts, posterior synechiae, especially if you see banned keratopathy, I would start immunomodulatory therapy essentially immediately along with their topical steroids. So where to go from here? If you're seeing this patient at a community clinic and you're not comfortable managing immunosuppression, send them to a uveitis provider or someone that is comfortable managing immunosuppression that works closely with pediatric rheumatology. And the reason for this is that studies show that early referral to a subspecialist in this patient population is improved with visual outcomes. So if you start them on topical steroids, the inflammation will get better and then you taper them and the inflammation will come back. So you feel like you're treating it and it's getting better and then it can be tempting to just leave them on four times a day prednisolone acetate but we know the risks of that with cataracts and glaucoma. So systemic immunomodulatory therapy have better outcomes. These patients need to be followed regularly even if they don't have any history of uveitis or any symptoms. And there's charts for the guidelines of how frequently they need to be monitored based on age, ANA status, duration of disease but sometimes it's as frequently as every three months. Refer early and dilate every patient with uveitis. This is our last case. A 30-year-old woman that notes some floaters in bullfies over the last few months. No pain or redness, no light sensitivity which has a past medical history of hypothyroidism. Social history is non-contributory. And vision is slightly decreased more so in the right eye. Antares segment is unremarkable when we look in the posterior segment we notice two plus vitreous cell with mild haze and one plus vitreous cell in the left eye. There's some nerve hyperemia and you notice some sheathing of the vessels and you look at the peripheral retina with scleral depression and you can see some exudates on the paris plana known as a snow bank. Immacular OCT shows a mild epiretinal membrane, some haze presumably from the vitreous cell and very mild macular edema. So we have vitreous inflammation, optic nerve involvement and macular edema. It's tempted to call this pan-uveitis this often gets referred in as pan-uveitis but this is really just intermediate uveitis with secondary posterior findings such as optic nerve edema and macular edema. This is not posterior uveitis since there's no inflammation in the retina or forehead itself. So this is just intermediate uveitis. Causes of intermediate uveitis, number one is idiopathic. It's not associated with any other systemic disease or infection. Next is sarcoid and then multiple sclerosis and then less likely is infectious ideologies. Could this be pan-uveitis or posterior uveitis and it's just a hazy view and we can't see the retina or coroid well enough to see if there's inflammatory nodules or lesions that's possible. So I think it would warrant doing fluorescein angiography or an ICG to look for posterior involvement. This is a wide field angiography of the right eye. We can see there's optic nerve leakage and then in the periphery we can see this fern-like retinobascular leakage which is very classic for intermediate uveitis. Workup, I would do a good review of systems. Ask carefully about neurologic symptoms since we're worried about MS. Ask about infectious exposures and things like cough shortens the breath for sarcoid. For laboratory imaging, I would get the typical labs ruling out sarcoid, syphilis TB, a chest x-ray, consider other infectious ideologies depending on their exposures and then it says neuroimaging only afforded. So we know multiple sclerosis is on the list of possible causes. A lot of times I'm asked to get an MRI of the brain for every patient that presents with intermediate uveitis and the answer is no. I only do neuroimaging if they have symptoms such as intermittent numbness, weakness, and an extremity or if I'm starting anti-TNF therapy in a patient with intermediate uveitis, we know these medications can worsen demyelinating disease. So if we think they have just idiopathic intermediate uveitis but we're starting, whom are I would do an MRI of the brain? So parsplanitis is the term used for idiopathic intermediate uveitis with exudates on the pars plana. These are the classic findings which we've reviewed. Here's some interesting facts about intermediate uveitis. So smoking is a risk factor for increasing macular endema in patients with intermediate uveitis. So that's just another reason to tell your patients to quit smoking. Up to 10% of patients with MS develop uveitis, most commonly intermediate uveitis and having uveitis it makes someone 18 times more likely over their lifetime to develop MS relative to the general population. I think this is just the fact that autoimmune diseases do run together. Management for intermediate uveitis, you can do periocular steroid injections, intraocular steroid injections, oral prednisone I use often if the patient presents bilateral active disease. There's evidence for laser photocragulation or cryotherapy to the pars plana. Immunomodulatory therapy in chronic or recurrent disease and then considering a vitrectomy which can be diagnostic if you're worried about infectious causes and there's some evidence that vitrectomy can be therapeutic as well. So my clinical pearl for intermediate uveitis, not every single vitreous cell needs to be treated. With anterior chamber inflammation we like to see the cells go to zero. However, with intermediate uveitis often patients can have a few vitreous cells if they're not bothered by their floaters, if the vision's good, there's no macular edema. The FA doesn't show leakage in the major arcades and there's no findings on FA such as meat vascularization or non-provision. We can just observe. So maybe someone comes in with trace vitreous cell, minimal haze, good vision. You do a work up and it's negative. You could observe that patient without treatment. Absolutely dilate every patient with uveitis. All right, that's the end of this lecture. I do have another lecture coming called posterior uveitis diagnosis not to miss. So I would encourage you to watch that one as well. Thank you.