 All right, so we're gonna get started over here. Hi everyone, my name is Tony, I'm a third year OpFM resident and I will be introducing our students today who will be presenting. First up, we have Vivian Han and fun fact about her is that she trained with the Olympic ping-pong team in elementary school, yes. And she'll be presenting today first, go ahead. Thank you, Tony, for the introduction. Good morning, everyone. I'm so grateful for the opportunity to be here. And this morning, I will talk about adjustment pains, specifically, explanation of a light adjustable lens. This is how our Manless Warner Lab is set up and I wanna first take a moment to thank Dr. Warner and Dr. Manless for their incredible support and mentorship throughout our past five months here. And also a huge shout out to Mary who's been a lifesaver in the lab. These are the grants that support the analyses of Explanted IOLs in her lab. As you know, we have a problem which is refractive surprise after cataract surgery. This is the third most common reason for explanting an IOL and the possible causes are interpatient differences in wound healing, postoperative shift of the lens and prior refractive surgery. Unfortunately, in eyes with previous refractive surgery, the best formulas reach within a half diopter of the target only 69 to 79% of the time. And the incidence of refractive surprise is only increasing with time as more patients who've had refractive surgery grow older. The technology of LALs has great potential for addressing refractive surprise. The RX site light adjustable lens is the first and only FDA approved LAL back in 2017. And FDA study of 600 subjects showed that eyes with LALs were twice as likely to attain 2020 uncorrected vision as compared to those with standard monofocal IOLs. And this is the light delivery device called LVD. It's a modified slit lamp that provides noninvasive UV treatment to adjust the LAL. And each adjustment consumes 10 to 20% of the macromers and can provide up to two diopters of correction. And these studies to test the safety of the LAL were done in our lab. And you can see Dr. Werner here treating a stuffed animal. And this video demonstrates how the LAL is adjusted and locked in. If I can play it, can you go back? Okay, it froze, we're good. It is based on photochemistry and diffusion of the silicone photoreactive macromers distributed throughout the LAL. And when UV light is directed to a specific area of the lens, the macromers in the path of the light polymerize. And then each treatment takes about 90 seconds and can last up to two minutes. After polymerization, the remaining unreacted macromers diffuse over the next 12 to 18 hours into the space. And that causes a change in the shape and refractive power of the lens. And so the light treatments can add or subtract sphere and sill. And then further treatments can be performed as long as there are untreated macromers left. And then when the adjustments are to the satisfaction of the patient and doctor, the entire lens is treated with higher intensity UV to lock the rest of the macromers in place, which you see right here. And it's mandatory for the patients to wear UV glasses from surgery up until after 24 hours after lock-in to prevent uncontrolled polymerization. Recently, an explanted LAL was sent to our lab for analyses, which we will delve into today. The patient was a 61-year-old man with no prior ocular history, including no refractive surgery. He presented to an outside ophthalmologist with increasingly blurrier vision in both eyes. His ophthalmic exam was normal, aside from 2050 uncorrected distance vision. He batted to 2050 minus one in both eyes and he had a two-plus NS in each eye. They planned for cataract extraction and LAL implantation in each eye one day apart, and both surgeries were uneventful. This was the examination on post-op day two for the right eye and post-op day one for the left eye. Litlampic exam was remarkable for three to four plus stromal edema in both eyes, three plus defaults in the right eye and one plus in the left. Both eyes also had two-plus cell. The next day, the patient reported that his vision in the right eye decreased in surgery and that he could only make out light at this point. Of note, his vision in the right eye went from 2,300 from the previous day to unable to be tested. And his litlampic exam was the same as the previous day and he was started on combination drops. At post-op week one, he reported distorted vision and photophobia in that right eye. His visual acuity was hand motion and the corneal edema NEC cell had not improved since the first post-op exam in the right eye. Meanwhile, his left eye was healing nicely and at this appointment, the blurry vision in the right eye was attributed to the persisting corneal edema and then he was continued on the combination drops. Unfortunately, at post-op week two, he presented with right eye pain. Examination of this eye revealed that IOP was 28 at this point and the cornea exam had slightly improved from the edema and defaults but now he had microcystic edema. His right pupil was also dilated and this clinical picture was attributed to a congested or narrow trabecular mesh work due to the corneal edema and then the pain was attributed to the elevated IOP. He was given 500 milligrams of acetazolamide at this appointment and serial eye drops of Cymbronza and Timbalol. And then at the end of this appointment, his IOP was 11 and he reported that the pain had ceased. And then the patient was given Cymbronza to take home and then he was referred to Dr. Mifflin for a DSEC. Dr. Mifflin saw him around post-op month one and the patient reported only light perception in the mornings at this point with improvement throughout the day to be able to make out shapes in the evening. The slit lamp exam showed worsened corneal edema as well as diffuse endopigment and then the pupil was tonic and dilated to six millimeters. So the exact ideology of this significant corneal edema and this patient was not clear. However, whenever we see acute early inflammation and persistent corneal edema, especially without surgical complications, we highly suspect toxic anterior segment syndrome or TAS. And it was presumed in this patient's case to be TAS as there were no other likely etiologies. Dr. Mifflin performed a DSEC with iris synechialysis and the histopathology of the specimen revealed pseudophagic boluscaretopathy as expected. Unfortunately, at post-op month six, the patient was dissatisfied with the vision and his best corrected vision was 2060. The optometrist went ahead and attempted the first light adjustment, targeted at Plano, but noted that there was poor dilation. As you can see, a week later, the refraction didn't improve much and testing revealed a large, just noticeable difference in refraction of 1.25 diopters. And then they noticed that the patient adherence with the protective glasses were questionable. So given this uncontrollable adjustment, the patient was referred back to Dr. Mifflin for IOL exclamation exchange. Dr. Mifflin had heard that Dr. Manlis described difficulty in exclanting LALs, so he decided to extend the DSEC wound to remove it in one piece. And he noticed intraoperative zonulurgia hitzens, so he implanted the new lens in the sulcus. Pupil's reclage was performed to create a 4.5 millimeter pupil. And then after the IOL exchange, the patient healed well. At the most recent examination, which was seven months after IOL exchange, the patient still had blurry vision with glare, irregular astigmatism, and irregular pupil. And he was referred for a colored contact lens to address the refractive error and to provide light blocking and improved cosmesis. Incidentally, the patient's left eye, light adjustments and lock-in were successful with satisfactory visual outcomes. Once the LAL was submitted to our lab, we and Dr. Ruth Saylor performed a series of analyses. Gross examination showed that the anterior surface had greater convexity at the blue arrow and concavity at the green arrow. And there are subtle distortions on the posterior surface as well. And then the microscopic examination showed a distinct round bump, approximately four millimeters in diameter. And you can see that it's de-centered towards the right highlighted by the white arrows. And the surface deposits just correspond to dried OVD and DSS. The scanning electron microscope confirmed the de-centration, showing the elevated position is more towards the right. And then light transmittance curves from mass spec show that the transmittance curve shape of the x-planted LAL, which is on the right, matches that of a normal LAL on the left. OCT evaluation showed that the shapes of both the anterior and posterior surfaces were very distorted. The anterior surface had greater convexity and greater concavity in different areas. And the posterior surface was convex and very irregular. This is the Air Force target image. And the right image shows the target image obtained through the x-planted LAL. As you can clearly see, the focus and contrast is significantly decreased. These are the results from Nemo testing, which is away from analyzer and maps the power of the IOL. The top left clearly shows that the changes in power are badly centered and shifted towards the right. And then the bottom right graph, you can see there's tremendous irregularity in the radial power of the IOL. So let's talk about x-planted LALs. There has only been one reported case of an x-planted IOL in the literature and it was in the left eye of a 57-year-old female. Her preoperative best corrective vision was 2025 and her exam was normal, except for cataracts in both eyes. Surgery was uneventful. Post-op day one and week one were normal. At post-op week two, the patient reported decreased vision in halos and her best corrective vision was 2040 at this point. And then the first UV adjustment was performed. However, at post-op week three, the best corrective vision decreased to 2125. The slit lamp exam showed distinct paracentral elevation in the LAL, which you can see in the photos. And they somewhat correspond to the decentration in our case. The patient at this point admitted that she had not been using the UV glasses routinely. And they ended up performing an IOL exchange, which resulted in a best corrective vision of 2025 and the patient was very happy with that outcome. Overall, this case emphasizes the importance of patient adherence to wearing the UV protective glasses. So LALs perhaps should be avoided in certain conditions because the macromers may polymerize in an uncontrolled manner. So as advised in the prior report, as well as by the company recommendations, patient adherence to the UV glasses are very important. Since our patient had uneventful light adjustments and lock-in in the left eye, it's likely that this wasn't the sole culprit in the right eye. And additionally, our patient had a mid-dilated pupil and the optometrist reported inadequate dilation before the light adjustment. So that might have promoted issues with the light adjustment. And then our patient also underwent a desec and as we know, different surgical microscopes have varying degrees of UV exposure. Our patient also had significant corneal edema, which precluded the first light adjustment and because of the easy view. And so, however, even once he got the desec and had a clear cornea, we know that corneas that have had a corneal transplant may influence and distort the light adjustment. And of course, if a patient can't hold steady for two minutes at the slit lamp, an LAL would not be appropriate. So although the exact reason for the LAL distortion in our case is not clear cut, it's most likely due to a combination of these first four factors. This photo shows how incredibly easy it is to explant an LAL. And this was from another patient and it was explanted by Dr. Manlis, who will gladly tell you how fun this was. Even with the lightest pressure, forceps would break off little pieces of the LAL whenever you tried to hold it because it's so hard and brittle. And then this was the LAL that Dr. Manlis explanted in the other eye and he switched to using a mini scleral corneal frown incision to remove the LAL in one piece. And the technique had less risk of astigmatism and also didn't require sutures. And Dr. Nicole Fram, who's worked a lot with LALs, described that while the LALs after light adjustment are hard and brittle, before adjustment they're soft and gummy. So anyone preparing to explant an LAL should be aware of these nuances. And Dr. Fram developed a new technique to remove these brittle LALs and she will publish them soon and is allowing me to present them here today. She creates a 3.5 millimeter wound because the lens is made of silicone and is very thick and may be difficult to remove from a sub-3 millimeter incision. As you can see, she injects plenty of OVD and then she dials the LAL to be perpendicular to the main wound, which is right here. And then she goes in with serrated scissors and she does in bisection in one cut and then uses a since the hook to provide counter traction. Then she dials at 180 to finish the bisection. And then she actually removes each piece using these serrated scissors. And this way, the LAL is very unlikely to break into pieces. From our patient, we know that unfortunately in complicated cases, the LAL adjustments can't be controlled well and may need to be explanted. There are quite a few explanation options that we've seen. So if we want to remove the IOL hole, we can do a 6.5 millimeter clear corneal incision like Dr. Miflindid or a scleral corneal frown incision like Dr. Mimilis. And then Dr. Fram's technique provides a smaller 3.5 millimeter incision, but requires bisecting the IOL. And RX site has recently improved the technology with the active shield UV layer. And it protects the LAL from unwanted UV exposure, which would help in some of these cases. And then Dr. Fram says that with this new technology, she's noticed that the LAL is less brittle after adjustments and that explanation has also been there. And this is just one adjustable lens on the market and there are several others coming down the pike as Dr. Mimilis alluded to on Translational Research Day. I want to acknowledge and thank each of these individuals and their expertise and hard work have made all of this possible. Are there any questions from the audience? Yes, Dr. Mimilis. And as tasks, you know, there's limits to limits to be in the first day. There's a dilated fixed pupil that doesn't do well. There's a ventral glaucoma later on as the information settles down. But I think the critical points you made are that if you're going to adjust the LAL have to have ideal conditions, you have to have clear media. And so do not try to adjust these to an edematous cornea, cornea that's had a de-sec, anything that's going to disturb the light coming through. Secondly, you need a dilated pupil. And you can see the de-centration of the treatment. You saw how irregular that treatment is. And so it's really clear in the company directions, don't do this in this setting. And so this should not have been done at all. But beyond that, once you go ahead to try to take these out, my first try at this, it's just brittle and it fractured into a dozen pieces. So I ended up taking out whole, which is fine. I think Dr. Fram's technique is ingenious with the serrated scissors because you just can't grab these things without them breaking off. And then you can't slide a normal scissors across because it just slides away. So I think the serrated scissors are ingenious in a way to bring this out, but we don't have those. And if you don't have them, a simple brown incision, which is the way we did cataract surgery in 1988, it's six millimeter, it's a little corneal splaral, mini corneal splaral frown, no stitches, no stigmatism. And so that's a nice way to get these out safely once you have to remove them. So is it clear for you what is the active shoe? And is it clear if the patient is going to have to change the wear of the protective eyeglasses before looking? What exactly is that? What the active shield is, is they put some, normally the way the lens was set up, the UV blocker is along a posterior surface because it really is a UV laser that induces the cross-linking. And so they didn't want us to disturb that. But when it was clear that some people were not wearing their UV blocking glasses at the time of lock in, they put a little layer of some small UV block in the anterior part of the polymer that will make it such that if they're not wearing their UV blocking glasses, the effect will not be as much. But they still have to wear it. Well, they stopped to wear it, it's just the effect is not as pronounced. All right, just one more thing, the Redmond stand-up lens for decades trying to get rid of the silicone lenses. This is back, I've already had one referred to me from the Montana or silicone one over here. Which I could not do, I would destroy the lens. And so if they have reds and polygons, they also fog, I don't know if they're as bad as other silicone lenses, but they fog when we're doing redness or something like that. So we need to silicone them. Dr. Mifflin just had a comment. Dr. Mifflin says, I am watching remotely and my microphone does not work on the chair mat. I'm 100% certain that the patient from this case who did not use the blocking glasses and had significant line exposure between the original surgery and the attempted adjustment. The lens was very bulky and difficult to remove from the capsule. I've removed one or two others earlier in the course of treatment and those two came out easier, but I elected to take them out both and block from a limo incision, cutting the lens in half similar to the office. Thank you so much Vivian for a great presentation. Also, thanks everyone for our similar session. To next up, we have Norma Doji. Just like Vivian, she's also a Pat fellow here this year and her fun fact is that she is an aspiring professional skydiver who's skydived in three out of seven continents and a couple of them in Dubai. So, welcome Norma Doji. Thank you, Johnny, for the kind introduction and good morning everyone for the opportunity to be here. This morning, I'll be presenting on a case that was sent just by Dr. Morgan Michaletti over at the Berkley Eye Institute in Houston, Texas. And so here are our financial disclosures and I just should know as Vivian did that these grants to support you now he would hide well in the cloud. And as Vivian just showed, this is an overview of what our Mamos Warner live structure looks like. Here at the Marin Eye Center and I also want to take a moment to thank Dr. Mamos and Warner for their tremendous mentorship and support. I honestly feel really incredibly lucky to be here. So, thank you so much for everything you've done for me so far. So, let's begin with our case presentation. We have, the chief complaint was, I'm not seeing well in my right eye. This was a 69 year old pseudo-fake Southeast Asian male with a history of technist, multifocal Iowa placement in the right eye about eight years ago in Vietnam who's presenting with symptoms of glare and changes in vision developing over several years. His past medical history was significant for type two diabetes for which he takes metformin for. His past surgical history, significant for cataract surgery in both eyes. As I mentioned, the right eye has a technist, multifocal IOL and the left eye has a monofocal posterior chamber IOL. He denies any significant family history and his social history is significant for tobacco use and is a retired jeweler. His, as far as his examination is visual acuity uncorrected is 2,200. In the right eye and then 2020 in the left his brushes are 15 in both eyes. Manifest refraction in the right eye showed a one diopter hyperopics sphere with a slight cylinder and then in the left eye, Plano with a slight cylinder as well. People's around and reactive in both eyes and there was no afferent people are defect and the exam was otherwise normal. On select examination in the right eye it was notable for brownish haze throughout the technist IOL as well as a nasally de-centered IOL. And then the left eye Dr. Micheletti noticed one plus PCO in a centered IOL. And so here's a video of the Sillimp examination. And so throughout the video you kind of can see this brownish haze throughout the optic. Some capsular like fibrosis of the capsular rexus excuse me and you see those mono or multifocal rings in the IOL as well. But that haze is very appreciable throughout the exam. As far as the posterior segment it was unremarkable and there were no signs of diabetic retinopathy. And so in summary, this patient is presenting with decreased vision and glare in the right eye. Eight years after implantation of a now nasally de-centered IOL with a whitish brown haze throughout. And so operative management was scheduled for an IOL exchange with a three piece IOL placed into the sulcus and Dr. Micheletti used the modified twist and out technique, which he actually published recently in JCRS and I'll be showing a video of that shortly. And so here's a video on a different patient that where Dr. Micheletti used this modified twist and out technique. I'll allow him to present it since it's published and then I'll make some comments at the end. Necessary, but so I think this slide on the patient and use of both hands of course that's vibrate both and you click on the page and it will develop that out in a secondary capsule like you got once a cat is created. I think only dispersive OEM and re-inclined the bag, I attack the habits from each side except in all of them, I need to have a collusion of facile. Once the habits are free, I need to set up the IOL out of the bag. Next, I specialize what happens when I'm in a position to IOL because not normally specialties realize that we all can. Protecting the helium and provide certain control of the IOL is a big amount of information. I took it 25 days from the month they said across the surgery for one site or another, which replaced me for the spatula and for you all. Now both hands can use with the forceps and more versus IOL free time. This says some of our patients fill out the wider top stop it as it replaces the large offer one new location with a two new technique. Yeah, so in addition to the other utilities he mentions about this technique, it also allows for ex-plantation of an IOL in one piece, which is optimal for laboratory analysis and worked out really well for the rest of this case. And so on post-up day one, the patient had a visual acuity of 2100 in the right eye with pressures within the same range that he had before presentation. And then on silt lamp, there was one plus corneal edema with a center three-piece IOL. Post-up week one, there was slightly improved vision at 2060 in the right eye with pressures the same and then improved corneal edema on silt lamp. And so we received the IOL dry in our lab in a plastic container and we were able to do a number of analyses. The first analysis was actually a light microscopy in the dry state of the IOL. And as you can tell, there are really no changes in the overall clarity of the IOL. It's completely clear, no pacification, no discoloration. This large blob you see is just dried OBD, so do not be alarmed. And then this mark over here is actually sustained secondary to maneuvering the IOL during ex-plantation with forceps. But overall, as I mentioned, no pacification, no discoloration and no changes in the clarity of the optic. We then placed the IOL in an immersion of distilled water at body temperature for 24 hours. And now we're able to see in the hydrated state, the IOL has a completely different appearance compared to the dried state. You see this brownish haze throughout the entire IOL extending all the way to the optics, I mean the haptics. And this was only present in the hydrated state compared to the dry state. While the IOL was in the hydrated state, we also did a shine flu photography to assess for backlight scattering. And as you can see, within the bulk of the optic, there is diffuse light scatter suggesting influx of water into the lens which is not supposed to be happening. We also did OCT in the ex meridian of the ex-planted IOL, although you're not able to appreciate as significant of a change as the shine flu photography showing there are some changes within the density of the optic. Next, we looked at light transmittance using spectrophotometry. And in the ex-planted IOL, the only noticeable difference was a progressive decrease, change in the light transmittance at about 500 nanometers. And unfortunately, we did not have a control lens of the same model and diopter to compare it to. However, we did compare it to the directions for use provided by the manufacturer for this model of a lens. And I'm gonna direct your attention to curve number two. And as you can see, although there doesn't have to, there doesn't appear to be a decrease in present transmittance at 500 nanometers compared to our ex-planted IOL, the UV values, which is this downward slope over here are the same in both lenses. We also did a modulation transfer function testing by the help of Dr. Saller, where when compared to our ex-planted lab to the DFU at both near and far distances of various people sizes, we see that there's overall no differences between the two curves. And then next, we looked at US Air Force targets of the ex-planted IOL. And as you can see, compared to what the photo the Vivian showed, both the distorted and the normal image, ours looks just slightly decreased in the contrast. And so for our discussion, I'm just gonna have you guys remember Dr. Werner's presentation last month during translational research day where she walked us through all the different things we've been able to learn from analyzing ex-planted IOLs. And so I'll be referencing various aspects of her presentation, as well as the literature to help guide us through what may have happened in this present case. And so first let's talk about optical clarity changes in hydrophobic acrylic IOLs. One of the things that we can see is during piggyback implantation, enteral and ticular opacification can develop. However, the opacitation that is occurring in this situation is actually centered in the between the two lenses as a substance or material between both lenses. And this substance actually comprises something very similar to what we see in PCO. Here's an image taken six weeks after two rabbit eyes were implanted with piggyback aqueous off implantation. And where you look at the black arrows over here, it's a beginning formation of this inter lenticular opacification. So it's developing between the lenses. I should note that rabbits are much more robust in developing cortical material compared to humans. But nonetheless, we do see this phenomenon when humans are implanted with two hydrophobic acrylic IOLs during piggyback implantation. Another phenomenon we can see is glistenings. I'll go into slightly more detail in the next slide, but I do want to show you what glistenings look like under sit-lamp examination seen here in the left image. And you're able to see these focal points of glistenings throughout the optic. And that's also appreciated over here on the right, which is a gross exam of a hydrophobic acrylic IOL that is demonstrating glistenings. We also can see surface light scattering, secondary to subsurface nanoglistenings. And these are best appreciated under Shine Fluid Photography where we're able to see changes in the anterior and posterior aspect of the IOL as these subsurface nanoglistenings are just concentrated within the surface and not in the optic-like glistenings. And so just briefly, glistenings essentially are fluid-filled micro-vacuoles within the IOL optic and they're usually present in an aqueous environment. They're about one to 20 microns large and they're seeing the hydrophobic acrylic IOLs as well as IOLs of different materials. And here are some sit-lamp examination photos of IOLs exhibiting glistenings. Here's a schematic just comparing the differences between the mechanism of formation of subsurface nanoglistenings compared to glistenings. And as you can clearly see, subsurface nanoglistenings are just within the optic as we saw in the Shine Fluid image here on the left. And then glistenings are contained within the optic itself. And overall, I do wanna note that none of these phenomena described so far can describe what is occurring in our present case. And this slide here will show that quite nicely. So on the left, we have a control lens with the Shine Fluid photography done with no subsurface nanoglistenings. Over here is a lens with subsurface nanoglistenings with its corresponding Shine Fluid photography demonstrating just the densities within the anterior and posterior aspect of the optic compared to our lens where we see this bulk scatter within the bulk of the optic demonstrating there is some hydration phenomenon occurring in our present lens that is not typical of subsurface nanoglistenings glistenings or any of their phenomenons I mentioned right now. However, when you do light transmittance and either subsurface nanoglistenings or in our present case, there is grossly no overt changes in the light transmittance of these lenses. On the other hand, we have optical clarity changes that are only seen in silicone eyewalls or so has been reported so far. And these changes can include surface deposition, secondary to calcium or silicone oil. We can also see opacification as a result of influx of water and Dr. Werner actually highlighted a series of silicone lenses that demonstrated this opacification about seven hours after implantation would be silicone eyewalls. And here's a slit lamp image of what was seen and then here are the light microscopy photos of these eyewalls. And they actually look quite similar to what was seen in our case where you see this diffuse brown discoloration throughout the lens both on slit lamp and light microscopy. And in this scenario, this discoloration was found to be secondary to contamination from exogenous molecules found from fumigants that were used in the storage facility that the silicone eyewalls were in. A similar phenomenon of brown discoloration was seen in early silicone lenses in 1991 published by Malouskas where they were found to be related to a manufacturing process. Interestingly, Wong et al actually reported a series of 16 eyes with brown discoloration of the hydrophobic eyewalls two of which actually were the same exact style as our lens, a Zimbu lens and the rest were still from the same manufacturer. And overall these presented one to 327 days after implantation. So quite different compared to what was seen in the silicone eyewalls I just showed. And the discoloration actually could not be attributed to any clinical cause and none of the eyewalls required explantation. They did do lengthotomy Q testing and although it was abnormal of the patients, none of the patients reported any changes in color perception. And so what happened in the present case that we just discussed to lead to the observed reaction? So considering the lens has a diffractive optic and was de-centered, it is difficult to establish any clinical significance of the discoloration. It is possible that the discoloration is related to light scattering due to water vapor diffusing throughout the lens. So the lens is exhibiting this hydration phenomenon since the brown discoloration only occurred in the hydrated state. And this could be secondary to manufacturing process. So while our current analyses do not allow us to establish the exact etiology of the discolorations, surgeons should be made aware of this possible finding with the ZmBu lens, design and carefully assess signs and symptoms before deciding on explantation. Interestingly, actually right before AIO we did receive this image provided by Dr. Wolsey of a symphony lens. So by the same manufacturer with this central localized discoloration of the IOL observed on Siltlamp examination, although it was not clinically significant for this patient, Dr. Wolsey did decide to explant the lens and she actually sent it to us shortly before AIO. So we haven't done any analyses yet. So don't wanna keep you guys on your toes but I will let you know what we ended up finding. I also wanna take a moment to acknowledge everyone that helped out with this presentation would have been possible without any of you. So thank you so much. Thank you for your time and I open the floor for questions. J&J, now that you may see this aspect but you cannot panic before really checking if it's clinically significant that it's very clinically feasible and there are cases already reported and this one we put in allies because the lens had to be explained because of other problems like especially the de-centration but it's very feasible. But before you decide for explantation check carefully about the clinical significance. Thank you so much for your time. All right, thank you, Nora. Thank you everyone else. And last but not least we have Brian Simon who is a research fellow at Dr. Tien's lab here at Moran Eye Center. All right, so my name is Brian Simon. I did med school at Loyola in Chicago and I'm doing research here with Dr. Tien on the fifth floor, studying retinal ganglion cells. Today I'm gonna talk about a project I did in med school. It's about trends in temporal artery ultrasound and biopsy at a tertiary care center. I have no disclosures. These are my objectives for my talk and I'm gonna start with a case. So this patient presented to the VA emergency room. He was an 80 year old male veteran with the past medical history of hypertension, systolic heart failure, AFib, diabetes, mitral regurgitation, right subdural hematoma in 2020, migraines and tension headaches. And he presented to the ED with four days of sharp left temporal area, 10 out of 10 headaches that felt like the worst headache of his life. He also described them as different from his past headaches. They gradually increased in intensity over several hours and then wax and wane. They radiated to the bifrontal region and over to the right frontal temporal region. They improved some with Tylenol but did improve with sleep, massage or gabapentin baclofen that his primary care provider had given him a few days prior. So he also had associated jaw pain and soreness with chewing. He had soreness with raising his shoulders, fatigue and felt off in the past week. He didn't have any weakness, weight change, light sensitivity, emesis, diplopia, dysarthria, numbness, tingling or gait disturbances. His ocular history, he was followed for a history of diabetes. He had bilateral PVDs and cataracts bilaterally. He wasn't taking any ocular meds and had never had eye surgery or a history of trauma. He was seen actually a few days prior to presenting at the ED at one of our satellite VA clinics just for a four year follow-up. At that exam, his acuity was 20, 30 on the right, 20, 25 on the left, pressures were 10 and 10. He had no APDs. He just had a single blot hemorrhage in the inferior temporal periphery on the left. And so the plan was just to follow up on the diabetes with a dilated exam in one year and presented to the senior resident clinic for the cataracts. So back in the ED, the patient's vitals were unremarkable other than some tachycardia. And his exam was also unremarkable. He had some cervical perispinal muscle tenderness, but his neural exam was otherwise completely normal, cranial nerves intact. They didn't dilate him, but his fundoscopy had no papillodema. His ocular motility was full. They got a CT of his head that showed no acute hemorrhage. And then the labs were grossly normal other than an ESR that was normal high range and a CRP was also normal. So at this point, the differential was still kind of broad given his history of the headaches. We included the migraines and tension headaches, but also he had that stroke in the past. So there could be some other intracranial process going on. Other systemic things could be rheumatoid, lupus, malignancy, systemic infection. He had that jaw pain. So you have to include dental disease. And then of course, vasculitis such as giant cell arthritis. So neurology was consulted. They recommended a migraine cocktail, continuing his home migraine prophylaxis. And they thought it was likely a tension type headache, but they wanted to consider giant cell arthritis and they can consult the rheumatology. He was admitted to neurology and his repeat ESR was elevated to the borderline for his age, which was 40 for an 80 year old man. Rheumatology then thought it was likely GCA with polymallid rheumatica symptoms. And they started him on IV, cellumendrol and they ordered the temporal artery ultrasound. So I'll talk a bit about temporal arthritis. It's the most common primary systemic vasculitis in adults affects medium to large vessels, median age at presentation is 75 years. It's more common in females and white northern European patients. There's a possible genetic predisposition, but there could also be an infectious or endogenous trigger such as calcification in the arteries. And it involves both a systemic inflammatory reaction and a local antigen specific immune response. So the pathology involves inflammatory cell recruitment to the vessel wall, which destroys and remodels the intima. There's hyperplasia and then progressive occlusion of the vessel lumen. And that's what causes the ischemic symptoms of giants of arthritis. On gross pathology, you'll see nodular granulomidus inflammation with the characteristic skip lesions and then on microscopic, you'll see a cellular infiltrate that extends transmurally and possibly multinucleated giant cells. Most common vessels affected are superficial temporal artery, ophthalmic artery, posterior ciliary arteries and the vertebral arteries. So this is just an example of the microscopic path with pointing out a multinucleated giant cell and you can see the vessel lumen is being occluded or being decreased in size. And then here's an example of palpable palpable temporal artery that was very prominent on physical exam. So the ocular manifestations of this disease are usually acute unilateral visual loss. That's secondary to most commonly the arteritic anterior ischemic optic neuropathy. So that is from ischemia from the short posterior ciliary arteries, also commonly seen as central retinal artery occlusion. But it's important to note that GCA can affect anywhere along the optic pathway. So many patients present with again, acute unilateral visual loss. They could also have dythlopia or eye pain, ptosis and anisechorrhea. And then systemically, they could have temporal headache in up to 90% of cases. They might have scalp tenderness. They could have constitutional symptoms, jaw tongue, jaw and tongue claudication, proximal muscle myelogias and then symptoms of PMR, which our patient had in our case. On exam, you might see a tender or pulseless temporal artery. The ocular exam, you could have visual acuity of 2200 or worse, or APDs, dythlopia, and again, cranial neuropathies or other ischemic changes along the optic pathway. In labs, you'll see elevated ESR, CRP or thrombocytosis. So this is diagnosed in a clinical setting. The criteria include five main points and age over 50 years, localized pain in the head, a temporal artery abnormality, ESR greater than 50 and an abnormal biopsy. So as you all know, the gold standard for diagnosis is the temporal artery biopsy, but the negative biopsy doesn't rule out the diagnosis and we often see false negatives. There's been many different imaging modalities tested in giant cell arthritis, including FAC, CT, MRI, PET CT, but in 1997, they first proposed using color duplex sonography to help diagnose GCA. It's proposed to be more safe and well tolerated than a biopsy. It's obviously a quick exam, not as costly as taking a patient back to the OR. You can repeat the exam if you wanna take another look at something. And then I think the most important one is you can examine the full length of the vessel and possibly avoid the problem of the skip lesions. So a quick review of the anatomy. The temporal artery rises from the external carotid and the main branches you're looking at in the disease are the parietal and frontal branches. The technique for a temporal artery ultrasound, you start at the level of the tragus with the ultrasound probe and you can sweep the entire length of the vessel in the transverse or longitudinal plane. Then you flip the probe 90 degrees and scan it in the other plane. On a normal ultrasound, you'll see pulsating and compressible artery. The lumen should be anechoic and the surrounding tissue should be mid to hyperechoic. That's an example of a normal ultrasound. Abnormal findings would be a halo, which is hypoechoic tissue surrounding the vessel lumen and a compression sign, which is an artery that doesn't compress with depression of the probe. You can also see stenosis or full occlusion of the vessel. So that's an example of a halo sign. You can see the hypoechoic tissue surrounding the vessel lumen and the lumen getting compressed. This is an example of a normal compression sign on the top with the vessel disappearing upon compression. And then with the halo sign on the bottom, with the wall swelling, the vessel does not disappear on compression. So back to our case, patient got ultrasound the next day. This is right temporal artery in the transverse view. You can see clear intimal swelling and this is a view with the Doppler flow. So you can see there's still some flow. It's not completely occluded, but there's clear intimal swelling. This is the same vessel in the longitudinal view and this is the artery upon compression. So the compression sign was positive as well. So this patient was on the IV steroids. They had improvement of their headache, jaw pain and scalp tenderness. Their transition to P.O. steroids and they actually deferred a temporal biopsy given that they had already kind of cinched the diagnosis with ultrasound and then follow up labs for normal. So the last few minutes I'm just gonna talk about our project. We looked at the usage and utility of ultrasound at our VA facility and it had four main components. The first part was a literature review to see how useful the ultrasound has been at other centers. The first study we found, this is just a brief overview of our review but in 2004 meta analysis of all the studies available to that date showed the ultrasound had a sensitivity of 69% and specificity of 82% compared with biopsy and then another meta analysis in 2010 showed that the sensitivity was 75% and specificity was 83% compared with the biopsy. So they actually recommend at that time using ultrasound for first line investigation. There's a few more studies. I'm skipped to this part. The study in 2016 also looked at reduction in permanent visual loss in their patients. We looked at 135 patients that they had scanned in clinic as opposed to using the conventional referral model and they had a reduction in permanent visual loss from 37 to 9%. And the same study also estimated the cost per patient for using an ultrasound compared to a biopsy could be reduced by over $600. Summarizing all the evidence we found with a reliable technician for the ultrasound the procedure can be as specific as a biopsy. It may be more sensitive than a biopsy and it may be more efficacious and cost effective. But again, it depends on a reliable technician and inter user reliability is a concern. The next part of our project, we implemented a new protocol with our vascular lab using this data we had reviewed from the literature. So this is just a snippet from that showing how we scan the ultrasound or scan the artery in our vascular lab at the VA. We implemented a new order in our CPS, CPRS system to make it easier to diagnose this. And then lastly, I'll talk about some of our data. So we looked at all the patients who had a ultrasound or a biopsy in an 18 month, 18 month period. We had 18 patients during that time. They were all male, mean age was 72 years. Their chief concern at presentation, half of them had visual change as their chief concern. Five out of the 18 had temporal headaches and then a few of them had other systemic concerns. So out of the eight ultrasounds we did, five of them also underwent biopsy. These ultrasounds were ordered by medicine department, a few of them were ordered by ophthalmology. And then seven of them were negative and one of the ultrasounds was positive. That was the case we talked about today. We did 15 biopsies during that period. Seven of them were done by ophthalmology but vascular surgery and neurosurgery also did. So then five of them ended up being bilateral taking both temporal arteries and the other 10 were unilateral. And we only had one positive during this whole time. That case unfortunately didn't undergo an ultrasound so we couldn't correlate it with the other procedure. From all the cases, two patients were able to defer a biopsy after a negative ultrasound. So maybe using that screening ability of the ultrasound to kind of rule out the diagnosis. We did see concordance between the five negative ultrasounds and biopsies. And then we had the one confirmed positive. Finally, in the treatment of the disease, 11 of the patients were started on IV steroids and switched to PO. Five of them were actually just started on PO steroids. And two of them had no treatment. Those were the patients who had negative ultrasounds. An important point is that steroids were continued even after a negative biopsy in 10 out of the 14 patients who had biopsies. And that's because it's a systemic inflammatory response. So it's important to even continue the steroids if the temporary is not affected, other vessels could be. So limitations, small sample size, and we don't know if our sensitivity and specificity are the same as reported values. So we got to keep looking at it. I was able to talk with Dr. Roger Harry for a few minutes last week about how you use ultrasound here at Moran. So I've just accumulated a few things I learned from him. So try to get the scan before you start steroids because the wall edema will respond quickly to those steroids and the ultrasound becomes less useful at that point. Again, a negative ultrasound doesn't rule out the diagnosis of giant cell. You could still have inflammatory cells present in the vessel and positive biopsy, even if the intima edema has gone away and the ultrasound's negative. And finally, order both ESR and CRP. One of these lab values could be normal, but the other one could be highly elevated and Dr. Harry has seen that in the past. So basically in the future, we're gonna continue collecting more data and then a few interesting things for ultrasound in the field in general. You're already doing this here at Moran, but point-of-care ultrasound in the clinic could help identify a lot of these patients and hopefully avoid biopsies. And in the future of time, we'll just end here. Thank you for everyone for having me to speak today. And I'd like to acknowledge my team at Loyola and the people at Moran who did this possible. Thank you. All right. If there aren't any other questions, thank you everyone. And have a great day.