 All right, you guys, good morning. We're going to get started, because we have three great docs today, two fellows and one of our neurosurgery residents. So first off, Chris Kamansky, one of our first few retinophels is going to start us off talking about a classic case of sympathy. Thanks for the introduction. So I'm going to present an interesting case that I share with Dr. Vitaly and Dr. Shakur. So the patient's chief complaint is he came in complaining of macrosia in the right eye. His history of present illness is that he's a 35-year-old man with a past anti-history rupture globe in the left eye 27 days ago. He woke up in the morning and noticed his eye. Their vision was a little blurred in his good eye. And that images were distorted in a way as if he was looking through a magnifying glass. He advised pain in both eyes and reports no change in vision in the left eye. His past knockout history, as we just discussed, was ruptured globe repaired by one of our other presenters today, excellently. With u-real prolapse, it was a nail gun injury while at work. His past medical history was not contributed to family history. It was not contributory. Social history is he works in construction. It's uninsured. His current health care is being covered by workers' compensation. He lives at home with a wife and four children. He lives, say, at a tattoo three years ago, but it's not raised or erythematous. He traveled outside the US numerous times in Mexico, most recently six years ago. He was born in Mexico, moved to the US at the age of six. He spent one week incarcerated in FJL in Las Vegas. He has three cats, occasional alcohol use, and denies high-risk sexual behavior or intravenous drug use. His medications are penicillin acetate four times a day in the left eye, known allergies. So on exam, his visual QD is 2060. This was down from two weeks previously when it was 2015. And then in his left eye, he was bare LP. His pupils were round and reacted to light in the right eye, 5 to 3. It was unable to be obtained in the left eye due to a 75% high FEMA, but there was a relative after pupil area defect by reverse. His real visual fields were full in the right eye, unable to be obtained in the left eye, and a pressure of 11 in the right and soft in the left. This is his anterior segment exam. It was unremarkable in the right eye, except for Trace Hayes and the anterior vitreous. In his left eye, we see a photo from a later visit, but it shows that he is resolving a FEMA, the eyelids, 2 plus injection of the conjunctiva. He has nylon sutures inferiorly. And at the time I saw him, he had about a 75% high FEMA. And the posterior structures were unable to be visualized in the side. This is a color from this montage of the right eye. And what we can see here is that there's some Trace vitreous Hayes. The optic nerve is normal. There's a normal coursing caliber to the vessels. However, attention is drawn to the macula, where there's these creatinine sub-retinal infiltrates and then maybe more punctate lesions in the temporal macula. There's also, if there's a stereoscopic view, you can see this pigment of demarcation line. And these actually are areas of retinal elevation and around the optic nerve as well. This is an OCT macula, the right eye. And this is an enhanced depth image as well. And the media is, again, clear. This disruption of the normal foveal contour with this large cystic space within the retina. There's areas of hyperreflectivity of the outer retina, as well as sub-retinal fluid throughout. And important to note is normally we can see the scleral hyperreflective band around here, but the cord is so thick in that you cannot appreciate the sclera on this enhanced depth image. These are other representative scans through the macula. Through the superior macula, you see a large collection of sub-retinal fluid and a nodule on the RPE. And now we get a better appreciation that there's these septated macrosyst within the retina and that are in the different layers. And then inferiorly, we see another large collection of sub-retinal fluid. Performed angiography, and in the ICG angiography, the early image is grossly normal, maybe some shadowing in the areas of sub-retinal fluid collection. However, in the later images, around 10 minutes, we see these punctated areas of hyper fluorescence throughout the posterior pole and around the optic nerve. On the fluorescein angiogram, there's a normal arm to retina time. However, at 41 seconds, we can see the emergence of these punctated areas of hyper fluorescence throughout the posterior pole. We didn't have, we lost them for a few minutes because it became nauseated and was vomiting in the bathroom, but then came back and we got a later image. And what we can see is there is some leakage from those punctated areas of hyper fluorescence, but most notably there's pooling in these sub-retinal fluid collections. And then even pooling within these septated macrosyst and you can see the hyperfluorescent areas, this line where the septa are between these intra-retinal cystic spaces. So at this point, I'll open up to the residents for a differential on this patient. Brad, what do you think? It's history, I think. Perfect. Anything that you would wanna rule out to make sure that's not just a confounding thing that might be a little dangerous to treat with steroids. Yeah, so it's infectious, you mean? Absolutely, so good job. And then there's just a more complete differential for exudative retinal detachments, but I believe this is much more likely to be sympathetic ophthalmia. So the assessment and plan is this patient has sympathetic ophthalmia in the right eye. We did the following lab workup, so CBC, CMP, RPR, FT-ABS, Clonk Gold, ACE, Lysozyme, HIV. You don't wanna get chest X, right? Pending the negative RPR and FT-ABS, we're gonna start oral steroids and have them come back in two weeks to initiate immunomodulatory therapy. So at this point, I would like this to talk about sympathetic ophthalmia because it's a pretty interesting disease. So it's incredibly rare. Ranges from 0.1 to 3% of ocular trauma. In about 70% of these cases are accidental trauma. In about 30% of these cases historically are induced by surgery. And with vitro retinal surgery being the most common and the most up-to-date incidents would be about 0.01%. What's interesting is that that breakdown changes based on setting and time. Well, historically it was more in the 30% induced by surgery. It's climbed to more in the 40% range at this point versus if we look at more international data, which probably has more to do with less ophthalmic surgery being performed there and maybe a higher incidence of trauma that those are more of the classic numbers of 70 and 30%. So I really went down the rabbit hole with learning about sympathetic ophthalmia because a lot of the literature is very old with sympathetic ophthalmia. And you can really see some interesting observations about how much caring for the eyes changed over the last 100, 150 years. And the incidence of sympathetic ophthalmia due to accidental trauma when there was very little care really that could be offered these patients was quite high. As high as 2% in most of literature prior to 1900. In the early 1900s about half percent. And then up until about 1965 then we really saw decreasing incidence after ocular trauma as surgical and medical intervention for trauma improved. And then the most recent that around that 0.1% of eyes. Similarly, there's been a big change in the incidence of sympathetic ophthalmia after intracular surgery. These are some older numbers but there's some of the actual studies that looked at this perspective. And cataracts in 1969 are very different than they are now but even back then it was an incredibly low rate and probably just lower today. And protracted me a state about the same and a 0.02% range. So about one in 10,000 cases. The mechanism by which sympathetic ophthalmia occurs is a T cell mediated autoimmune response and there are certain HLA associations. The most notable in our population is HLA DR4. It's really a complex disease with stages of an active inflammation and chiescence and recurrences can be months to years to many, many years later. So the key questions I had when learning about this case and taking care of this patient were what is the appropriate immunomontratory therapy? What are the indications for a nucleation of the inciting eye? And then what are the indications for surgery or surgical repair of the inciting eye? And again I went down the rabbit hole and I learned a lot about history and I wanted to share some of the things that I learned about. So while sympathetic ophthalmia is kind of a, sounds like a fairy tale disease that you tell to scare your children from getting injuries to their eye because you could have an injury to one eye and then once maybe even years later you could lose the vision in your other eye. So this was written about as far back as Hippocrates but in Western literature the first mention of it was by George Bartisch in the German literature in 1583 and I included it because it was the first mention in Western literature but also because he was a barber surgeon. So he had no formal education and at the age of 13 he became an apprentice in a barber shop and that's how many surgeons came into the career and this is a picture of him couching an eye in the 1500s so things have changed a lot. Now the first detailed write up of the presentation, the thoughts of the etiology, the prognosis of these patients came in this pretty thorough write up by William McKenzie in 1840 and this is considered the time when there was a renaissance in ophthalmic knowledge and I had a quote from this and it really reminded me that people used to write differently in the medical language than they do now and I just wanted to share it so. Whenever I see sympathetic ophthalmia even in its most first stage I know I now contend with an affection which however slight in its present symptoms maybe is one of the most dangerous inflammations to which the organ of vision is exposed. I wish I could write like that. So just a few years later part of this renaissance were kind of a newfound goal of treating eye disease and Dr. Pritchard published in 1851 the first advocation for enucleation as treatment for sympathetic ophthalmia and so the idea would be if you observed the symptoms of sympathetic ophthalmia you would enucleate the inciting eye and this is important because for the next hundred years this was the only real treatment for sympathetic ophthalmia. In 1911 Dr. Elschnig who is a huge fighter in ophthalmology hypothesized that sympathetic ophthalmia was an immunologic disorder. This is a really important distinction because up until this point it was believed that something happened within the inciting eye and maybe it was some type of infectious process. It would travel down the optic nerve through the chiasm back down the contralateral optic nerve and then infect the sympathizing eye and so Dr. Elschnig's belief that maybe there's an immunologic mechanism by which this is happening was a really paradigm shift and this would then guide us for the next hundred years of how we've thought about it. This leads us to when the treatment migrated away from enucleation and surgery as the only way to treat sympathetic ophthalmia and while this isn't from the ophthalmology literature it was a huge discovery in medicine and that's in 1948 doctors Kendall Henschen-Rickstein had found a way to synthesize and then came up with the idea to administer corticosteroids to a patient with rheumatoid arthritis and amazingly just two years after the initial publication they received the Nobel Prize. So it was a landmark study and this two years later is when the first use of steroids were used in the eye and as we'll see that had pretty major effects on how sympathetic ophthalmia was treated. So this is another quote and I think it was interesting some of it isn't as applicable to today but however the reasons for you doing local so they came up with a topical subjunctival injection as cortisone as well as a topical coliseum or drop and they identified that there was going to be less danger of a systemic reaction they thought the cost is possibly less but they didn't know we were going to have a luvian and ozard X so maybe systemic steroids are a little cheaper and they used to have to hospitalize these patients who were getting systemic steroids and then probably not true but interesting that their goal that local treatment could be continued almost indefinitely and certainly a higher concentration was possible this is the original publication of steroids being used in the eye and we're not gonna go through all the details but they used everything from ureocyclitis to scleroceratitis and then now at the bottom you see the first three cases treated with sympathetic ophthalmia and this is what the point I wanted to get to with this article published from Mass Eye is that when you look at the number of cases of sympathetic ophthalmia and then you look at when steroids were introduced to control inflammation either after surgery or after trauma not only is this a treatment for it this was pretty convincing that this may actually decrease the incidence of sympathetic ophthalmia and then looking at the outcomes for these patients before steroids were available only about 60% would maintain 2100 or measured vision versus 90% after they started using steroids so dramatic improvement in care and now this fast forward to article published in 2018 of 130 cases at a multi-center case series and let's talk about where we are now because after steroids we eventually developed immunosuppression as a way to control this disease long term and looking at the patients that steroids are used in almost every patient so 98% and then immunosuppressants and 70% of these patients and the centers are in the UK, India and Singapore. In terms of what type of immunosuppressants it really is mostly dominated by the use of anti-metallids and in this series it was acetylprenum but in the US it would be methotrexate or mycophenolate. With most of these patients being controlled on zero or one long term immunomotorotoy therapy I was interested in that the nucleation of blind eye in the modern series was still pretty high and especially when you look at in the UK with 50% of the inciting eyes being in nucleated. In terms of just looking up in the book these are the mainstay of first line treatment so the anti-metallides and then psychosporin, second line being anti-TNF biologics. So that talks about how we can manage this from immunomotorotoy therapy standpoint and then I got really interested in understanding the reason why a nucleation can be treated. So this is the data from the 1980 publication from Mass Eye which looked at and argued for the possible nucleation of the inciting eye if there's no visual potential in it. And what we see is that the time of the nucleation and final visual could be better than 2070 and what they found is if patients were nucleated and they're inciting eye within two weeks of the onset of symptoms of sympathetic ophthalmia so this is not from their trauma but from the onset of sympathetic ophthalmia that 74% of patients maintained better than 2070 vision versus if it was more than six months it was down at 50%. But it was more I think enlightening to look at when you compare the untreated cases versus the steroid cases because in the series they included patients from way back in 1913 who were treated with steroids and when you look at the untreated patients if it was less than two weeks to a nucleation 81% maintained good vision versus if it was more than six months it was down at 17%. So pretty dismal outcome if you didn't get a nucleation early and you didn't have steroids but once there's access to steroids that those numbers came a lot closer together and now with modern immunomodulatory therapy it's felt that there's not a difference. And then this is the article that was arguing for that and they found that in 2000 a nucleation of the exciting eye was not related to any visual outcomes and it didn't attribute any resolution of disease and there was no significant difference in the maintenance corticosteroids for these patients. And now the last question I had is are there additional risks for trying to repair an inciting eye? And this is another 2018 article that was published and they reviewed the literature and what's really interesting in the sympathetic ophthalmia literature is it's not uncommon for the inciting eye to actually be the better seeing eye long term. And so that really caring for the inciting eye as much as the exciting eye is very important. These are the four cases that they had and three of the four cases, two of the four cases for trauma, two of the four from vitrectomy. They surgical interventions afterwards there's one PK, one clock coma drainage device, one oil removal and one vitrectomy and so silicon oil tamponade. And what was found is the patient who got the PK their vision improved dramatically and the patient who got the clock coma drainage device their vision was 2040 and it stayed about 2040 and the patient who got the oil removed their vision stayed about the same around 2200 and then in the last patient their vision went from hand motion to NLP. So one patient did not do well. But this argues that it's very important to care for the inciting eye as oftentimes good vision can be maintained. So when we look at our patient his inciting eye status as he was light perception without projection he had a RAPD and as I was soft his B scan shows a close funnel RD emitting to the wound in a thickened cord. And so it was felt that this I had very little visual potential and so at this point he's just being observed in his left eye. In terms of this clinical course we can see his presentation and then just after three weeks of steroids how dramatically he's improving and his vision went from 2060 to 2040. And then now four months later his vision is 2015 minus two and he has a pretty normal looking retina. There's a little bit of ellipsoid zone change in outer retina. But he's doing great. He's on 25 milligrams of subcutaneous methotrexate each week. He's off steroids and the plans for two years of immunomodulatory therapy after the cessation of steroid and at which point he'll be discontinued and observed closely. I'd like to thank you for having me today. These are my references and this is my son. Any numbers on time of incidence of sympathetic after initial trauma can occur years later? Absolutely. There's a case of it occurring 43 years after presentation. However, about 80% of cases happen between two to three weeks and three months. And then about 90% of cases are within a year. So most of them happen. There are outliers though of them happening many years later. So Chris, should we be dilating open globes like in follow-up of their other eye? Should we be looking for this or is it something that's typically just presents symptomatically? I think that's the answer is that they have symptoms and if they have symptoms in their other eye, absolutely, we need to look at it very closely. Which was really interesting in this case is that oftentimes they don't present or aren't able to get to us, especially all that quickly. And so this patient had had an excellent globe repair at the Moran just three weeks later, presented the same morning, was able to be seen in a UV-itis clinic and get a full workup. So the imaging was really interesting here and the treatment started very quickly. And having an outcome of 2015 vision is what we're really, really happy with. So I think getting therapy started early is important. And so counseling patients, if they ever develop symptoms in the other eye after they've had trauma is, I think, really a key aspect of it. But yeah, I don't think dilating every month for months would be likely to change how we find and treat it.