 and our cornea fellows. We're gonna go in a little bit different order than what's listed here. So we're actually gonna start off with Dr. Weinlander with a new technique for scleral suturing devices. And then I'll give a brief update on the effects of COVID on corneal transplantation. And then we'll end the presentation, our end grand rounds with Dr. Gudgel with a case presentation. So I'll let Eric take it away with the first case or the first presentation. All right, thank you very much Dr. Weinlander. So I'm sure I've met everybody at this point. I'm Eric, corneal fellow. I'll say Brett the other introduction, he's the other fellow. So I'm gonna talk a little bit about a technique that we've been working on to help with scleral fixation. And specifically we're talking about scleral suture fixation. So this is a really broad area within ophthalmology. So basically a suite of different techniques to suture things to the inside wall of the eye, smear lenses, capsule support devices, our Espresse CCs, other hardware, many, many, many different techniques for this and many different variations on these techniques. So we're gonna kind of give a bird's eye view a non-exhaustive list of some of the important core elements and sort of what led us to want to adapt to challenging clinical situations. So one really important thing to consider is sclerotomies or access to the vascular sulcus of the fixation point. You can look at these sclerotomies readily used to circumferentially. There's many different ways to make it, different tools that you can use, but essentially the main point is it needs to fix at the lens in an appropriate position. You need to have easy friction-free, trauma-free access with instruments and the suture through the sclerotomy and you really need to be careful to avoid any damage to the retina or uvial tissue, which is close by avoid ripping off the ciliary body, avoid causing a supercroidal hemorrhage, avoid hitting the ciliary body, causing a vitreous hemorrhage. And then at the end of the case, they do need to be watertight. And over years and years, ideally your wounds should support long-stir stability and a coverage and burial of the knot for your fixation suture. In addition, the method with which you introduce and externalize the suture can also play into intraoperative complications along with term stability. Sort of two large categories that tend to be dominant for sclerotocuture fixation. And this is the docking or railroading technique or the handshake or grasping technique. So in the docking or railroading, you have an ab external guide needle, which is shown in the picture on the right and an ab internal fixation needle. And you dock the two intraocularly and externalize. The handshaking or grasping, you have your sclerotomies externally and you have a grasping or a snaring or some sort of instrument like a snider grasper, condensnare or what have you to actually grasp the suture internally and externalize that through the sclerotomy. Again, the requirements are very similar to those of the sclerotomy. The agent needs to be safe, predictable and a traumatic. Then one of the other important element is making sure that once you have made a hole in the eye, got a suture through the hole, making sure that you can talk appropriately and bury it. And there's many different ways to do this. The probably safest and easiest is to internalize the knot through the sclerotomy. You can do what's called a Hoffman or corneus scleral pocket where you do a partial thickness limbular dissection where you hide the suture knot underneath the partial thickness flap. Or you can make a larger flap or you can do these knotless suture fixation techniques. All told, needs to be stable, needs to minimize the suture erosion. And in my opinion, I think you do need to tailor your means of burying the knot to the patient and the health of the tissue and those sorts of things. So right at the beginning of my fellowship, we faced several challenges from a series of patients who were aphagic, avitric and needed a penetrating carotoplasties. So kind of a perfect storm for intraoperative complications. And we faced a lot of the challenges, not just in the learning curve and inherent to these techniques but things specific to this patient population that sort of made me rethink how can we make this approach safer for our patients and for this patient population in particular. So with any of these techniques, you can have issues where the sclerotomy leaks post-operatively and you get post-op hypotony, you can have uveal injury intraoperatively and this risk goes up the more you manipulate at the sclerotomy, the bigger the sclerotomies are at the larger instruments you use, the more timely or hypotenuse or open sky. What can we do to minimize intraocular injury, avoiding things like multiple sharps docking inside the eye. And then sort of as a side note, what can we do to help reduce reliance on micro-instrumentation? I mean, they're fantastic instruments but they are prone to mechanical failure and their own problems. And again, this issue of a long-term suture coverage. So sort of the challenge that we faced, what can we do to minimize these risk factors for this patient population? And this is a potential solution that we came up with. It's called the suture needle snare, super catchy name. And this is made with a 27 gauge needle nylon suture that runs through the lumen of it. And you dock this on to an empty three CC syringe, essentially using that as a handle. And the idea is that you're introducing a loop of 809 on suture into the eye that you can use to then snare and externalize your fixation suture. With this device, we pair it with a 25 gauge needle sclerotomy that's connected by a partial thickness scleral groove. The reason for using 25 gauge is we found that that is the smallest size that can accommodate a Gore-Tex knot. And the needle, because we feel that that architecture is most self-sealing and the least traumatic. And the general approach in this technique, I mean, it's still based on the same principles of scleral suture fixation. First and foremost, citrus management. And then you make your sclerotomies and then you introduce your means of externalizing the fixation suture, introduce the thing you're fixating and then finalize disposition and tying barrier knots. Diagrammatically, it looks kind of like this. So we have the suture needle snare in the upper left. You can see we have the 27 gauge needle with the 809 on suture running out of it. So a needle and the suture running out of it. And you introduce it through the sclerotomy. You create a loop inside the eye. You externalize this loop of suture. We use a Sinske hook. You can use any hooking instrument and you could even use a grasping instrument. And then once you have this loop external, you can feed the fixation suture through the loop, withdraw the needle, withdraw the fixation suture and this internalizes your loop of fixation or withdraw the snare suture. This internalizes your loop of fixation suture and then you withdraw the whole thing out the sclerotomy, ending up with a fixation suture that's running in the appropriate place. So to help visualize this, we have a video from a case. This is a patient, an older gentleman who had initially had a PK for post-lacycocasia, which subsequently failed and he was left aphacic and he had a SAS post-antibiotectomy with the failed PK. All right, so we start by marking two points, 180 degrees apart. We've already done our pyrimies. And then we're marking 1.5 and three to 3.5 millimeters back from the surgical limbis. And we're doing this in a radial fashion with the lens that we're gonna fixate, which is the Bosch Alarm MX-60. We feel that doing a radial fixation reduces or eliminates concerns of lens tilt. As our partial thickness scleral groove, then this is the 25 gauge needle to make the sclerotomies at 1.5 and three to 3.5 at the ends of the scleral groove. Next, we're preparing the lens of the Bosch Alarm MX-60, amputate the haptics and then we feed our CV-8 Gore-Tex or expanded polytentative floor ethylene suture through the eyelets at the base of the haptics. Since we're doing a repeat penetrating keratoplasty, we're gonna take advantage of the opening in the old PK. And here I'm introducing the suture needle snare through the posterior most sclerotomy. I'm making sure I'm inside the 25 gauge needle sclerotomy and you can see it is a fairly frictionless atraumatic entry into the eye. So we have the tip of the 27 gauge needle in the 80 nylon suture in the AC. We're externalizing. So there's the suture in the AC and we're externalizing the snare suture through the main moves. Then we're gonna pass our fixation suture through that loop of nylon suture. And once we have that through the loop of the snare suture, the nylon suture, we're going to withdraw the needle and gently provide some traction on the snare suture to internalize the two loops and then externalize the fixation suture through the sclerotomy. Now we have our fixation suture where we want it in a relatively atraumatic fashion. Now we're able to repeat this maneuver for the remaining three fixation points, making sure that we're on the appropriate side of the fixation sutures internally and that we're externalizing the appropriate suture through each sclerotomy. We're repeating this for the inferior fixation points and for the final fixation point here. And at this point, we leave the fixation suture a little long, but that's not a problem as you can just externalize the tail end through the sclerotomy. Then we're inserting our lens through the large PK wound and centering it. And we temporarily tie it and perform a penetrating keratoplasty which we did through in seconds in this video at least. And at the end, what we don't have is we finalize the knots under minimal tension and are able to internalize, trim and internalize the knots through the sclerotomy and then cover with our perotomy. Okay, back to the slide. So again, diagrammatically, this is sort of the overview of the technique. And thinking about what we were setting out to do with this way, this means a scleral fixation. We're trying to, again, minimize our risk factors for leaking sclerotomies and tissue injury. We're trying to minimize our alliance on micro instrumentation and avoid multiple sharps in the eye and enable a complete burial of the suture. We feel that using the 25-gauge noodle sclerotomy and then having this particular snare lets us use a 25-gauge sclerotomy because this is much smaller than that and it's fairly atraumatic. We were able to do the whole case without actually any infusion because we started making the sclerotomies in a closed system and using a 27-gauge noodle through the 25-gauge sclerotomy allows for this. We're able to use minimal to no specialized micro instruments, potentially increasing the applicability of this technique to settings in which these resources aren't available. And for a full-taken scleral using 25-gauge noodle sclerotomy is helpful. We do have one intraocular sharp but we at least don't have two. So hopefully that increases the safety. I'm just gonna spend a minute here talking about other suture snare techniques. There really is only one. After we were working on this, we looked back into the literature and we did find that there's a report from Sunpec Chi from Singapore. She's fantastic anti-segment surgeon. She described a similar snare technique using a Gore-Tex through a 26-gauge needle in a Hoffman pocket. We feel that our approach, her approach is excellent and very innovative. We feel that our modifications helped to make this more amenable to the particular patient population we were faced with, namely a setup for a super parietal being a vitric, a phagic and needing to be open sky. In her technique, she does use a Hoffman pocket which we feel is not always amenable or not always the best option for patients needing scleral suture fixation, especially if you'll be open sky because it's a relatively friction semi-traumatic entry into the eye. In patients who have an underlying connective tissue disorder or you have worry about a partial thickness flap covering Gore-Tex for years and years, you may want full thickness burial so you really shouldn't use a Hoffman pocket. In addition, we feel that our approach of combining, of doing a separate 25-gauge therotomy and then introducing the snare rather than in this approach using just a single needle to enter the eye enables a frictionless atraumatic entry whereas you have to introduce a needle wrapped in Gore-Tex in the former. And we feel that as atraumatic as possible of an entry is beneficial particularly in the patients we were faced with. And then finally we think that using a separate snare material so using nylon for the snare and Gore-Tex or purlene for the fixation suture is beneficial certainly in the beginning of the learning curve where you have multiple suture ends on the field and you're just trying to keep things straight. So having a separate material for the snare and separate for fixation can be beneficial. So in summary, we feel that our variation on the snare technique which we're calling the suture needle snare is a good low-cost effective means of sclerofixation that minimizes surgical risk factors for sclerotomy leak, tissue injury and uvial injury and it is particularly helpful in these avitric, aphacic eyes and especially in patients who will need to be open-skied during the procedure as we feel that this is a fairly atraumatic way to sclerofixate the learns. Downside it does require a thorough retracting passing open suture loops through the eye. If you snare vitreous is a recipe for disaster so you need to be confident there is no vitreous as with any scleral suture technique. And the steps of creating the suture needle snare is a potential learning curve and this idea of introducing multiple suture loops can certainly be a stumbling block to start. But we do feel that this technique can serve as a useful addition to current scleral suturing and sclerofixation techniques. So with that, I'd like to thank everybody who helped out on this, especially Dr. Lin. And I really wanna highlight the lab Janet Iwasa and Grace Xu. So this is an on-campus lab that works in medical animation and they actually provided all the vector drawings for this project. I'd also thank Ethan for very patiently and multiple times going back through the video. And I'd like to thank the various sources that also helped to support this. So yeah, that concludes my presentation. I'll take any questions, any feedback and any thoughts. So thank you very much for that presentation. That was great. I just wanted to credit Eric with actually coming up with this. I was voicing a lot of the frustrations with kind of the known scleral suture techniques that we were dealing with. And there is the Yamani technique but that is not amenable to open sky in my opinion. And I've heard of just, I didn't even attempt it because I've heard that there have been just it doesn't work well in an open sky kind of arena. So this has really, I think maybe revolutionized the way we do scleral suturing. So we just wanted to kind of let it be known that this is something out there that I think a lot of people should try. So this is Dr. Olson. I, you know, and Eric, I think that was fantastic. And it's a fun for me to look back and see how this has evolved back from when we started to suture support of secondary lenses. And when that was very controversial and the 10-0 proline was the go-to suture until we realized that didn't last that long. And that we still had a lot of them last a while but sitting about eight, seven, eight years out you started to get breakage and disappearing. And it just applaud all those have been involved in how this field has continued to evolve and move forward and watch these elegant techniques in comparison to some of the things that we had to deal with in the old days has been really pretty fascinating. So thank you for presenting this new approach in particular for a suture like Gore-Tex which I think that far and away has the best chance of a suture fixation technique that is going to stand up to the test of time. Thank you. Hey, any other comments, questions before we kind of switch gears to my presentation? Excellent talk. And I look forward to hopefully publishing this soon. All right. I will go ahead and share my screen. Hopefully you guys can see my presentation here. You can see it. One of the such gears completely does something different, a little update on what's going on in the world of cornea. And we know that COVID has affected just about every facet of life as we know it. And I wanted to discuss the effects of COVID on corneal transplantation and specifically the effects of changing donor screening guidelines over the course of the pandemic and how this has affected actually our donor tissue supply. And then at the end of this, I'll talk very briefly on potential side effects of the COVID vaccine on patients with existing corneal transplants. So as we know, March 11th, 2020, the WHO declared COVID-19 a global pandemic. However, I banks around the world, even before this date began to implement new screening guidelines to really minimize and reduce the unknown risk of donor to recipient transmission. And actually a month before this, in on February 3rd, 2020, the EBAA, which is the I bank Association of America came out with its first set of guidelines related to the coronavirus. And this was actually, believe it or not, before COVID-19 was the official term for COVID-19. So at the time it was based on travel to endemic areas and close contact with a confirmed infection. And then over the next few months during the spring, there were further updates to the donors as the pandemic became more and more widespread. And as we knew more and more about the virus. And so there were actually monthly updates through the spring. By May, the donor screening guidelines had become more conservative. It was really travel became less of an issue because COVID was everywhere. And it was more based on PCR testing, signs and symptoms of COVID potential, other alternative etiologies of their symptoms, whether or not there was close contact. And that determined donor eligibility. As you can see in the kind of right hand corner of this. And by this time, I bank medical directors such as myself or being consulted on a pretty much daily basis by our local I banks with questions about whether very specific donors were eligible for transplant. And I, along with I'm sure many others were airing on the side of deferring donors for transplant, being very conservative just because again, we just don't know the risk of COVID transmission from donor to host and no, I bank and no medical director wants to be responsible for the first recorded case of COVID transmission via donor, infected donor tissue. So in October 2020, this has been the most recent set of guidelines that we are currently working off of. It's just a little bit kind of different from the previous slide in May. And the I banks have become a lot better about ruling in or ruling out donors for transplant without medical director review, but there are still instances kind of as you can see in the right hand corner where medical directors will be involved with making the call as far as whether or not a donor is eligible for transplant. And there have been a significant number of donor tissues that are excluded because of medical record review. That percentage has come down over the past several months. It was at a high of about 9% deferral rate back last spring. Tours the end of 2020, the rate has been around maybe an average of 6%. We don't have data for the last few months of, you know, the beginning of 2021, but there's still a significant number of deferrals. So I wanted to go, I didn't really go into specifics about the PCR testing requirements. So for donor eligibility, a COVID PCR test is considered relevant if it is done within 28 days prior to death and up to 24 hours after death. The EBA actually does not require post-mortem PCR testing of its member iBanks. There are some iBanks around the country that are doing it. We are not. However, if it is done post-mortem, the EBA will accept test results done within 24 hours post-mortem. So when would a PCR test be done post-mortem? So it is being done in cases where the donor is also being evaluated for solid organ transplantation. So the organ procurement agencies will perform post-mortem PCR testing. Or if a donor is a medical examiner case, the medical examiner will perform a post-mortem PCR test. However, the validity of category testing is unknown. So thankfully to date, there have been no reports of COVID transmission via donated itissue. However, this has not been the case with solid organ transplantation. So in the fall of 2020, there was a patient in Michigan who died of COVID two months after receiving a double lung transplant with tissue that was actually infected with COVID. It, scarily enough, the initial test was negative, which is why the tissue was transplanted, but it ended up testing positive later on. And even more scary, the transplant surgeon actually became sick with COVID. But thankfully was, thankfully recovered. So this is a very scary situation that we don't want to deal with with eye donation, with corneal donation, but we think that the risk is very, very low. So this is a, the results of an article that just actually came up in this month's cornea journal, showing that there was an absence of the COVID RNA and corneal tissue. So this was a study done in Germany on five donors who had expired from COVID. And they show that there was negative tests in the, PCR tests in the corneal stroma and endothelium, all of our congenitiva, congenitival fluid swabs, anterior chamber fluid, corneal epithelium. And the average time between death and sampling was 21 hours. So this is all very, very reassuring that there is minimal or negligible risk of, of COVID transmission through eye tissue. Another thing is povidone iodine is actually used for just during tissue recovery. And povidone iodine red has been shown to readily inactivate a coronavirus infectivity on a logarithmic scale with exposure times as short as 15 seconds. And the EBAA medical standards actually had been updated to do a double soak of povidone iodine before the pandemic. The reason for that, for that change, because it was just a single soak before was to really minimize the risk of fungal keratitis and ophthalmitis after corneal transplantation. And so now the EBAA medical standards have been updated so that there's two soaks of povidone iodine 5% for two to five minutes soaking the entire ocular surface, letting it sit there, then it's rinsed off with sterile saline and then another two to five minutes soak is done. So that has been found to reduce the chance of kind of fungus and bacteria, but also with the coronavirus. So going back to the effects of donor, changing donor screening guidelines on cornea, donor tissue supply. So these two graphs kind of show what has happened over the last year of 2020. So as you can see, the left hand graph shows 2020 corneas recovered with transplant intent. And you can see that in April 2020, there was a very low number of corneas actually harvested with transplant intent. And a lot of this has to do with the lockdowns of elective surgeries during the spring. And our donor screening guidelines actually reflected that as well. And very similar curve in the actual number of corneas that were used and transplanted with a big dip in April. As things opened up, the numbers have come back close to pre-pandemic levels, especially with the actual number of corneas transplanted. There is a dip in November, December. I think this is a normal thing that happens every year, just with holidays and fewer operating moon days being open. So it's been great that we've seen the rebound in transplants. However, I wanted to point out this light blue line here. So this is a line showing US graphs that are actually used internationally that are shipped internationally. And you had a similar dip in April here, but that level has not really come back up to the pre-pandemic levels. And a lot of that has to do with a lot of travel restrictions, which I'm actually going to go over in the next slide. So 2020 overall, donor corneas. These are corneas that were harvested with transplant intent. It was down 20% overall from previous year. Actual cornea transplants performed was down overall 23% from the previous year. EK's were down 30%. EK's were down 16%. April had a probably record low number of domestic transplants, only 822 transplants were done in the entire US in April of 2020, which is 19% of normal. Many iBank functions were curtailed internationally, and the actual tissue, then if you look at the numbers of tissue sent from the US internationally, that's actually down, it was down 43% in 2020 compared to 2018. Many other logistical issues were present in 2020. There were delays with getting results of post-mortem testing, just with the labs being inundated with a number of tests being performed overall. The reduced flights also affected the transport of corneal tissue around the country. The reduced flights also affected cargo, and they were shut down on certain days such as the weekend. So that affected the transport of tissue. And so there was a lot of reliance on ground transportation with FedEx and UPS, but they were also dealing with a surge of in deliveries, not just from tissue transport of course, but with I'm sure everyone online shopping. And meanwhile the Postal Service was dealing with all the above, but also dealing with all the election-related mail that was occurring in late 2020. So all of this had resulted in delays in the release of corneal tissue and also the time from death to transplant. So I wanted to stop there and see if anyone had any questions on this thus far before I kind of switch gears to talking about the vaccine effects. So no questions. Okay, that's great. So the next slide of talking about the COVID vaccine and potential risk of transplant rejection. So there have been several anecdotal reports of transplant rejection shortly after receiving either the first or second dose of the COVID vaccines. And on our care net corneal surgeons forum, email forum, there's actually been 15 reports around the country of transplant rejection. So there's going to be papers about this coming out in the coming year, I'm sure. But given this potential risk, they're actually considering recommending increasing a topical steroid frequency in patients with corneal transplants starting one week before the patients receive the vaccine and continuing for at least one week after the vaccine. I haven't seen any rejection after the vaccine, thankfully. And I've seen several patients coming back, you know, just for their routine follow-ups. They've had a PK and the PK looks great and they have received both vaccines and no issues. However, in light of this new knowledge, I am recommending that patients come who have not received the vaccine, just telling them to increase it prior to and after the vaccine dose. Obviously, I'm obviously strongly recommending that all patients receive the COVID vaccine. And this is not a new issue. There are other vaccines which have been associated with increased risks or rates of rejection, such as with the flu vaccine and the shingles vaccine. So I wanted to kind of pause there as well. I only had one other thing if we had time with a just an example of kind of the little mini dilemmas that I deal with with our iBank with a ruling in or ruling out corneas for transplant. So any questions by anybody before I briefly go over that. So this is just an example of some of the email exchanges that I have with my iBank. So this was in back in November and this is the friendly email I got from our iBank. So it says we have two donors from this last week that were both OMEs, so Office of Medical Examiner Cases. Both donors passed on 1031. They did not have COVID tests done by the OME until 11-2, which is outside of the EVAA's 24-hour post-mortem testing. Both of these tissues are allowed for cases tomorrow. OME has not received the results from the Health Department on these two donors. Both of these donors did not have any signs or symptoms of COVID. Do you have any concerns releasing these donors without the COVID-19 test results? The test would not be valid anyway due to EVAA standards. So the first donor was a 30-year-old man who was found down with a single gunshot wound. Second donor was a 29-year-old man involved in a hang gliding accident announced on scene. So I read this. I responded and I said okay to release both donors for transplant. So probably about an hour later I received this email. It says after releasing the 29-year-old male tissue, I received an email from the OME with the results from the 30-year-old male. The 30-year-old male COVID test actually came back positive. However, this is well outside the 24-hour test time. It's still a positive test. We did not release this donor given the positive test. But I'm wondering how to approach these situations given this is most likely not a valid result. So my response was in light of the positive test, I agreed with not releasing. I guess if this happens in the future, I would release the tissue only if there was a negative result of a previous pre-mortem or valid post-mortem test. And also nothing else going on with symptoms or close contact. So these are not cut and dry cases. And so we got to make these calls regarding potential COVID in our donors. But thankfully I think the risk is extremely, extremely low. But again, we just want to make sure that we really don't want to have any potential risk of infection. Okay, so that's the end of my talk. I'll take any questions if there are any. Otherwise, we will continue to Dr. Brett Gudgel with his case presentation. Okay, can y'all hear me? Well, I am Brett Gudgel. I'm one of the other cornea fellows. I just want to give that kind of a brief case presentation and also kind of do a little brief discussion too. And in my talks title, why won't this heal? And so for our presentation, we have a 48-year-old woman she admitted originally for a GI bleed. So she's in the inpatient service and her chief complaint was that right eye pain and decreased vision. And this eye pain for off and on for about four months was actually seen by an eye care provider two days prior to admission and received it was diagnosed with a corneal abrasion and give it a bandage contact lens without any antibiotics. And since then, she feels like the pain is worsening and vision is declined as well. Otherwise, anxiety, depression, some allergies, some back pain, no surgeries. Other than in 1990s, had a chelazine excision, unsure which eye it was, family history is not contributory, social history, no alcohol use, does endorsed medical marijuana use and vaping. And you can see her medication list there. On exam, just at the bedside, so near without correction, she's hand motion at six feet and her right eye. On exam, we have a 20-25 in left eye. Pupils and intracranial pressure were both normal, mobility and competition visual field were full. External exam was unremarkable. The anterior exam on the left eye, uninvolved eye, was normal. On the right eye, just some highlights. There's some lid, erythema and edema. Notice some chemosis and what was described as kind of a ring infiltrates with about 50% inferior epithelial defects. In the anterior chamber, hard to tell if there was cell, really hazy view, but it seemed deep. And the posterior exam was unremarkable. So this is a photograph. It's, you know, hard to appreciate all the details, but you can appreciate some of that make an inferior nasal infiltrate. Epithelial defect does not really project, but then also some chemosis and injection there. A brief differential diagnosis is certainly not exhaustive, but, you know, we think in this situation, managed contact lens, not using antibiotic, admitted corneal ulcers, is bacterial, maybe incanthamoeba, also viral is always on the list, fungal, and then some other non-infectious step marginal, contact lens, associated keratitis, and things like that. So we proceeded with treating like kind of a typical ulcer, remove the damaged contact lens, culture that and the ulcer area started broad spectrum antibiotics and also psychologic for her license to be impossible, AC inflammation. So kind of briefly going over a clinical course. So we first saw in the 19th, the 20th kind of as expected, not really much of a change cultures not growing anything. 21st, the lid swelling is improving, the epithelial defect is improving. So she's actually kind of going in a good direction and start to kind of consider decreasing antibiotic frequency, adding some more lubrication, culture still not growing anything. And she's discharged on the 21st. On 23rd, she's seen in our corneal clinic, and there's a little bit of a decrease in epithelial defect, infiltrate has gotten much better. You know, in the typical intake process, get a little more additional history, she said, well, maybe I had this possible rash kind of around my eye on the right, a few years back hard to say it wasn't really treated with anything. And then on exam, besides the improvement in that field defect did note to have some decreased corneal sensation much worse on the right compared to the left. So that point continued to decrease the antibiotics increase ointment and lubrication. 26 a few days later, culture kind of finalized no growth at all. And there's really minimal change on the actual epithelial defect was kind of stalled out the borders are starting to get a little rolled pretty punched out or very well demarcated infiltrates improving though. And so with this appearance, you know, it's kind of more of a neuro trophic appearance at this point with the infiltrate nearly gone and so we started kind of going down that line of thoughts, taping the antibiotic some more increase in lubrication and kind of really protect the surface, you know, discuss all her options. She felt like she, you know, liked patching her eye at times to help light sensitivity and she'd also try the vantage contact lens off and on it kept falling out multiple times but she wanted to keep trying it. And with kind of this intermittent therapy she has significant improvement there's no thinning thankfully and she almost entirely healed which was very encouraging. She no showed multiple weeks of appointments try to contact her getting her plug back in four weeks later she shows up. So she has worsening pain her vantage contact lens had fallen out about a week prior. And now she has about 50% central corneal thinning in that area where the epithelial defect was nearly healed previously. So at this point with the thinning we discussed some more serious options for her, you know, recommended tarsofie versus maybe an ambiodisk which for those who aren't familiar kind of a dehydrated amniotic membrane wafer with a vantage contact lens, and discussed her option she was very very tarsofie adverse and so she wanted to go ahead and try the ambiodisk and so we placed that with the contour lens and also started her in doxycycline and vitamin C to try to prevent further care to lysis and thinning. And one week later she kind of canceled another appointment no showed another one, and she came in her vantage contact lens was out. Again, but thankfully that field defect was almost entirely resolved in that eye and the thinning was totally stable the corneal demon that she was having a hard time getting rid of had improved so she's done really well, but she said you know my left eye is pretty blurry now and she had no priorities she's with that so we look at it she has this new large central epithelial defect with corneal demon the left eye looked very similar to her initial presentation on the right eye. And so at this point I'm thinking you know something's kind of odd she's just losing his vantage contact lenses constantly I've never had someone lose so many vantage contact lenses out of all the patients I've seen and now it's bilateral. And so I think when in doubt me situations it's always important to kind of, you know, keep digging repeat history get additional history and so I asked her anything you could be using on your eyes anything you're doing she's well I've been using this hemplosion on my eyes. Every night. So it's like gosh I don't know I've never heard of hemplosion oil causing issues I did a case review on that couldn't find anything she's like you know I also kind of run my eyes every now and then. And so still kind of with when in doubt keep digging I did a chart review kind of really dove deep over the past several years and thankfully there's care everywhere on epic which is very nice find other facility visits and so she had multiple dermatology and emergency department visits. She was on skin concerns over the past, you know, six to seven years, pretty frequent multiple times, you know, month sometimes. The patient was pretty consistently concerned that her skin might be infested with something maybe a fungal infection. And she said sometimes she feels like there's warm like things kind of coming out of her eyelashes, very, very concerned about this. A lot of provider notes note frequent skin picking during their exams and lots of kind of sores around her eyes and eyebrows and sometimes these unfortunately get super infected with bacterial infections which you've been treating multiple times for. And so, you know, with this new information the next time I saw her I really kind of empathetically brought this up for her and asked you, you know, maybe do you think this is kind of contributing to your situation. And she very emotionally admitted that she has this very severe kind of compulsory urge to kind of pick at her skin and rub her eyes. She admitted that her vantage contact lenses would always fall out after she kind of would aggressively rubber eyes and she really felt like she needed a lot of help with this and she was really struggling and so I think that was really kind of a breakthrough moment for her care. And that discussion with her. So over the next month with all this new information that the patient really start working on these compulsive behavior she's kind of trying to get unplugged in with some psychiatric help and I think that's been beneficial for her. Her vantage contact lenses which would fall out, you know, almost immediately are now staying in. And with that her epithelial defects have entirely resolved in both of her eyes. She continues to have this like very dry irregular kind of neurotrophic appearance surface at the end so we're playing on some scleral contact lenses for her in the future to see if we can get her surface a little more protection. And so that's just kind of a unique case to kind of segue into that neuro-trophic care ties or care top in general which I think this patient at least has a component of that and so this is a degenerative disease at the corner of Philly I'm you know really kind of characterized by poor epithelial healing. It's a multifactorial pathophysiology. I think a lot of people, you know, immediately think of, you know, a decreased sensation leading to cold injury and also some decreased reflex tiering but there's also biochemical component where the neurotransmitters actually help promote regulated health and proliferation and lack of those can lead to these chronic issues. So many, many causes, you know, HSV, VZV are going to be the most common by and large, but there's also tumors that damage V1 distribution, topical medications, diabetes, and then the bottom bar list here chronic corneal injury inflammation which I think probably contributed to this patient's situation which is chronic recurrent corneal injury. So when you think of neuro-trophic care ties, there's really kind of three clinical stages. Stage one is going to be kind of punctate epithelial staining, decreased tear breakup time. Stage two, you're going to progress to more of a kind of a frank epithelial defect. Eventually over time this with chronicitis can kind of take that role, orders appearance. You can have some pretty pronounced stromal edema and cell inflares so that can kind of make the picture a little murky, kind of confused exactly what's causing this. And then stage three is when you start to have the stromal lysis and that can very rapidly progress to coronal perforation, which is obviously something we want to prevent. In terms of current kind of traditional management for stage one just lost lubrication, try to address any underlying, you know, things that are contributing to the issues like eyelid malposition. Stage two, start to kind of be a little more aggressive contact lenses considering a tarsaur, feces, serum tears, vitamin C, tetracycline, plugs. In this stage three, you really need to act pretty well. Stage two, you probably need to act pretty urgently, but stage three for sure you do. And that's when you start thinking more in your disc, prokaryotic membrane. If there's a perforation or near perforation that you consider gluing, tarsaur, feces always create conjugal flaps and then worst case scenarios you're thinking of penetrating keratoplasty strategy, you know, reform the globe essentially. And they kind of segue and that's kind of more traditional treatments, but thankfully some recent developments, both semi recent developments both surgically and non surgically surgically we have corneal neuroticization and non surgically there's some various growth factors proteins peptides that are kind of coming down the pipe. So in terms of surgically corneal neuroticization I've always thought this was a really cool procedure and this is actually the process of transferring a healthy donor nerve tissue to an area that is the innervated. And so you can use with the indirect method and autographed or even an a cellular nerve oligraft. There's multiple options for the cornea you can do super old on our super trochanal nerve and for oral nerve which really can be it's lateral or contralateral so really depending on the patient's anatomy and situation you have a lot of options. This is a really interesting paper by Dr. Langold and Duke and who did a kind of a good step by step of their technique and so you can see here, bilateral lid crease incision marks. So they're actually isolating this super orbital nerve. And then they attach the this in this case it's an oligraft and they sell your oligraft to the nerve, and then they pull that across the nasal bridge, and then externalize it on the contralateral side. And then they pull it through the lid to the conjointiva kind of split the oligraft into different segments, make a conjointival incision and bury this sub conjointively around the lindus, and then close that the thought is that this nerve tissue over that I think there was about an average of eight months can kind of re innervate the corneal nerve. So Dr. Park and colleagues did a kind of a review this is the large review I could find in the article pretty recent about 2020 that had 54 eyes various techniques various underlying etiologies looking at this and they found the both best rectal visual acuity and central corneal sensation approved for the patient patients who have residual limited best rectal visual acuity is often limited by corneal scarring. I think interestingly children seem to do better than adults I'm not sure if this has to do with kind of neuroplasticity or just their ability to kind of regenerate their nerves well, but that really I think pretty promising results for this kind of moving into the non surgical options survey which I'm sure most people have heard about before the FDA approved in 2018 commercially available in 2019 and this is a recombinant human nerve growth factor. So it's kind of promotes the growth and maintenance of corneal nerves also helps to sell proliferation migration, and it also starts to kind of help with the limbo stem cells as well. So there's two kind of I think really good studies that are in recent recently published once in 2018 this was the phase two randomized controlled trial they had 156 patients and they found about 55 to 58% demonstrated healing by four weeks this is based on different dosages, and they defined healing by less than 0.5 millimeters of residual epithelial defect at the greatest diameter. And then by eight weeks about 75% demonstrated healing and in the 56 week follow up here there's only 4% relapse rate in the epithelial defect. Recently there was a double blinded multi center randomized controlled trial with 48 patients and they found that 69% healed versus 29% of just the vehicle group by eight weeks. And then at 65% had complete epithelial closure so even more than that point five residual epithelial defect versus 16.7% placebo so I think there's some good evidence that shows this can really help on people. There are a couple downsides I mean what I have heard I've never personally used it or have had patients under my care that I've used it but it's not exactly user friendly apparently have to store this in a pharmacy freezer and kind of get your doses each week it's a multi step preparation process using multiple syringes and cost wise this is I'm not sure what the cost is honestly this is just a screenshot from good Rx and so with a free coupon, we can get it for $24,000. And so pretty steep there but I'm sure I've heard that the company has some good assistance program since I'm sure there's some ways they'll mitigate that cost. In terms of tolerance, most common complaint is eye pain but apparently through the studies this was pretty minimally impactful, and there's still a lack of longer term data which I think would be nice to know just how these patients do longer than the 56 week period. Moving on briefly kind of superficially covering some other things that are in development there's products called regenerating agents and these are engineered polymers and these are designed to kind of mimic stromal matrix and so when you have this chronic epithelial defect you start that stromal matrix breakdown doesn't really create a good environment that they're willing to grow and these are thought to kind of replace that and help create a good area for the epithelium to kind of close that defect. So there's a molecule called thymus in beta four and it's a protein that regulates essentially cell proliferation helps epithelial cells migrate muscle decreases inflammation. And there's a molecule called connexin 43 and this is a gap junction protein and this kind of helps facilitate intercellular communications and stuff that these intercellular communications kind of play a role in the apoptotic cascade that can happen with epithelial defects and so by inhibiting these gap junction proteins we can kind of prevent that apoptotic cascade from happening. And then briefly some other peptides and growth factor substance p insulin growth like factor insulin growth factor one in combination these two have shown to promote epithelial cell migration and attachment and then just regular insulin applied topically has shown to increase epithelial cell proliferation and inhibit apoptosis and all of these have, you know, in animal models and in very small clinical settings have shown to have some promising effect on epithelial regeneration neuro trophic eyes, but none of them have undergone large randomized controlled trials to really see how this goes. So the conclusion here some pros I thought I learned for these cases and situation I think neuro trophic erotopathy or keratitis is really something that almost every such as an ophthalmology will deal with and almost every such as we can even cause it, but there's topical medications, rental procedures, you know, trigeminal damage, it's something we see a lot of with that the initial picture can be super murky it's really difficult to tell is the bacterial is viral what's happening here. And even more worrisome this can progress very quickly to perforation and so in our case we you know the patient was also fall for just a few weeks and had a different thing and I'm sure that if we didn't see her even, you know, further out that she could have perforated easily. Like most things in medicine, even as a cornea specialist histories critical and I think the thing I love about ophthalmology is things almost always have to make sense it's a field that I think makes sense. If things don't make sense, I think it's very important to continue to dig until they do. And then there's like so many fields within ophthalmology some exciting advancements on the way and I think this is around that we can certainly use some additional help because this can be very difficult patients to treat. So that's that is all I have for us your my references. Thanks so much for your time. Thank you so much Brett for that really great review really great presentation. Dr degree had a question which I answered online. I just wanted to highlight you know if the nerve growth factor improves nerve fibers improving sensation and reducing pain. So I just wanted to clarify that you know it does improve sensation but it actually may increase pain in patients do that to that increase sensation so I know you had mentioned that Brett in your talk but I think it's, it could be something significant that patients should be prepared for as as they start something like observations. But really great talk and I think you had highlighted the importance of getting a really good history when things don't make sense. I think that's true for a lot of things, not just this case is really to dig deeper if if nothing's really getting better in patients. You know not improving the way that you would want them to. So I wanted to open up for any other questions from anyone else. Yeah, so obviously this has been a major problem for those involved in the corneal field for ever. And it's nice to see that slowly but surely we are starting to understand more and more about the problem and coming up with new means and ways of treating it but it's clear to me we still have a long way to go we a lot more we need to learn it would seem relatively straightforward to figure out what what it is that can be provided to maintain a normal corneal epithelial layer in the face of you know, not having a good overall sensory nerve supply. I know there's some interesting work I reviewed a paper not too long ago about to nerve transplantation that I know you chat a little bit about as but one way or the other I think we're going to get there but I think the recent flurry of activity suggested maybe sooner rather than later, which is a good news. All right, well that concludes our corneal grim rounds. Happy Wednesday everybody and we'll see you around. Thank you, thank you.