Chapters Transcript Management of Retinopathy of Prematurity: ICROP, Anti-VEGF, and Imaging Course: Current Concepts of Ophthalmology 2025 So we're gonna, we're just gonna focus on ROP right now and I think that more more than anything else this is, this is gonna be just an update for those of you who haven't, uh, seen this space who screens for ROP here? Anyone? Who, who manages patients who had ROP or, OK, so I'm speaking to an audience of like two people, um, which is great, but and also to, to the residents and and fellows, right, so, uh, here are my disclosures, um, and then. Oh, it's not showing OK, um, can we show the slides? Perfect. Uh, so a few years ago and actually this is right before the pandemic, um, we convened the, the ICOP, uh, the International classification for ROP Committee, uh, and this was help supported by, uh, IPOs and the Knights Templar Eye Foundation and some other groups, um, so international group, uh, and it was quite some time until we, we updated the, the classification system and, and this is the, the large group of, of really fun smart people that, that, uh. That came together and I'm just gonna give you some examples and some reasoning as to why we did this and to give you the definitions um that are updated that we have to think through from ROP perspective uh so here's an X23 weeker uh and again someone that was referred to me uh birth weight 700 g saw them at 15 months. OK, so in the past. Uh, we weren't resuscitating, and a lot of these children who were 23, 24 weeks weren't, uh, making it, so we're seeing more and more children who are born really, really young and really light, um, survive, but with that comes ROP. So this is, uh, a patient who had numerous antibud Jeff injections and we're seeing more and more of this in the anti-budgeff era, uh, suppress the disease initially, um, uh, halts the, the progression of, of treatment required ROP. But then develop this right so develop this pre retinal membrane and this isn't something that we would see commonly uh in patients who've had laser treatment, um, but we are seeing different manifestations of uh ROP and the sequelae of antibif treatments, um, as, as we've we've learned over the years, um, imaging as always has been more important in these cases so fluorescing andrography you can see the peripheral avascular retina, I think you can see it here. How it just stops and again this is not the common case that we see usually in in someone who's developing normally this is post anti redraft and you get this halted vascular development right? and what do we do with this? So just going back in time in the history of the ICOP, uh, started around 1980s, uh, with the cry ROP study, you know, which was really a seminal, uh, clinical trial and how we manage the disease and initially starting 1984 we had the zone stage plus disease, um, and then retinal detachment was then described and then in 2005, so you're thinking 20 years ago. Uh, we, we then described APROP, the aggressive form disease plus uh P+ and also discussing regression. And it's evolved right and in terms of why we now need this reclassification or an update uh to what we do, uh, it's for a number of reasons, OK, so one is our understanding of aggressive posterior disease uh we we recognize this early patients who had a lot of oxygen or micro preemies, um, but again our understanding of aggressive posterior disease evolved over time. Especially as we also started to work internationally and seeing aggressive disease happen in children who actually were bigger, um, and it didn't also happen uh posteriorly right you see aggressive disease that was more anterior in nature, so we had to think through that, um, through the work that a lot of us have, have done but also uh when thinking about the AI discussion and some of the work that Mike Chang has led, um, plus disease and our definitions around plus disease has changed a lot. Uh, before, I remember in my oral wards, uh, we had this picture of plus disease. I don't know if, uh, Cathy, you remember this, but is this one picture, right? And it was this binary discussion around this is plus or no plus. What we've learned through the years is that plus is actually a spectrum of disease, right? And it's a gestalt, right? So the day he's here, you know, you, you probably see these referrals, um, it's not always the same to the same person, and there's a lot of variability in what the examiner diagnosis as plus disease. Uh, so we brought together a group, uh, it was led by Mike, uh, and also with a number of ophthalmologists from around the world, both pediatric ophthalmologists around a specialist, um, a number of different countries, and we tried to, to make sure that there was diversity in their group as well, and these were the main additions, um, and discussions in that, uh, I crop, uh, uh, revisited so looking at APROP looking at the zone of disease, um, because many of us have. Uh, thought that posterior zone 2 is different from your normal zone 2, stage 5. This was really a push by Doctor Seal Ozdack from, uh, from Turkey, really interesting in terms of the surgical management of the condition, um, the plus disease spectrum, as I mentioned, um, and I think very importantly, I'm gonna focus a little bit on this later, but reactivation of disease. This has been a really hot topic. Uh, as, as we move forward, especially in the anti-va era, uh, because there's a lot of variability in how we managed it, but also a lot of variability in how we diagnose it, and I think that's very important and then this discussion is of course in the antivaf area of, uh, persistent vascular retina or par. OK, so here's the first update. Uh, we took the P out. OK, so APROP is no longer aggressive posterior, uh, it's just aggressive ROP, uh, and it's more determined by the, the tempo of the disease, um, so how quickly it advances, it can still advance through different stages and progress the retinal detachment, uh, very quickly, um, but it's not defined by the zone, right, or the posterior nature of it. Um, in terms of the, uh, the notch and how we define it, uh, there's, uh, a new diagram here, uh, which is the posterior zone two, so that we're documenting this in our clinical practice. Why is this important? I think that especially as we think about clinical trials in ROP space, making sure that the nomenclature is all appropriate and that we all agree on it so that we're we're talking about the same thing. Um, we've also recognized that there's a notch in the temporal quadrant, um, very frequently that will make something zone one, we think that these may potentially behave differently, um, so we think about natural history studies which, uh, may or may not happen, but also in the, in the treatment studies defining these so that we understand if there is a notch and you treat it, does it behave differently in the long term. Um, here again is the definition of the notch, um, but making sure that we document that and then of course, uh, to repeat it is the plus disease discussion, uh, which is now a spectrum, OK. Further with plus disease, uh, we put together this paper Gil Binnbaum really, uh, spearheaded this and it's done a terrific job, uh, down at Chop, um, he's actually gonna talk about this later today, uh, in the CCOI meeting. Um, but using something called the P score, uh, which rooted out of this I crop discussion, uh, you can see here the 9 figures, the 9, funnest images looking at the different, uh, vascular changes that they used to define plusness, uh, if, if that's a word, but we, many of us who screen for ROP will say that, um, and what it showed is that using these different images. You actually uh had a higher uh integrator agreement. Now this is important because through the years we've shown all sorts of variability in plus disease diagnosis and anything that can get examiners to agree upon a specific diagnosis is gonna help clinical care um we're also performing some studies around how this will uh pertain to educational interventions in our residency and training programs. So moving on in terms of uh the par, the reactivation discussion I think this is critically important um especially as we've had evolving treatment options uh for ROP so again this is more for the residents and and the fellows, you know, we started with freezing treatment, cryotherapy, we shifted towards laser shifted towards earlier treatment, and then now, you know, we use anti red. I think a lot of us use it pretty routinely in clinical practice, either it's primary treatment or it's adjuvant therapy. Um, anti-va F and imaging has been just game changing in our space. But the reactivation discussion I think is very important because historically we've recognized reactivation as something that can happen but one of the main issues is that as a community uh of people who treat this disease we never came to some general consensus around what the definitions were. OK, so if you look back in time pre I would say 2019, 2018, uh, people would publish papers on reactivation or management of reactivation, and there was so much variability in how they would define it, right? So then as a, as a general practitioner managing these, what do we do, right? There's no consensus. It's not like the EROP or the cry wrop studies which give us really clear guidelines around what to do. So one of the things that we did in ICrop was we try to create some sort of general definition around what we can define as reactivation of disease and that that's either post anti bad of treatment or just post laser, right? And um or you know if you have par, so it's recurrent vascular dilation, so if there's some change um in in the plus disease spectrum, if there are new vessels. And the extra retinal vessels can appear as a fibrovascular ridge. And again, the imaging is very important. Um, in terms of, uh, the treatment and timing, uh, of reactivation, uh, there's still some discussion around, OK, what drug may have more reactivation to others, the timing of your injections, uh, so in the beatrop study they showed that if you had aggressive ROP you're more likely to get reactivation, um, and then reactivation will occur later, of course, uh, with patients who have, uh, anti eF. Um, here's the recommendation, uh, regarding, uh, when reactivation occurs, so we recommend clinical monitoring up to 75 weeks PMA, uh, if you've had prior anti badF injections, and then of course if you have a fluorocene, and this is a big question in community, um, do one, right, because it does help, uh. In terms of how do we treat it, I think most of us will treat it with laser. I think what's interesting in in the community is that we will see patients who've had multiple anti badF injections just over and over and over again, right? And, and I think there's a concern for that um so for most of us I think if we do see uh enough normal vascularization out to the periphery. Uh, and there is reactivation, I think laser will stick and it's a good option to, to do that, which brings up the discussion. We still need basic indirect ophthalmoscopy of thumb ophthalmoscopic skills, right? So for those who trained for residency in order to manage this, right, so you need to you need to learn how to do laser. Some people talked about this dosing matter, uh, so in this case with, uh, the DRCR, you know, they've done a really good job in terms of looking at lower doses of bevacizumab, um, in this case it didn't show any difference if you lower the dose or not in terms of reactivation or, uh, how much reactivation you got. Um, in terms of persisting the vascular retina, this is something that we're also seeing more frequently, uh, and I think part of it is because we can see it, uh, with the imaging that we have either with fluorescent angiography or in the office, um, with those optus images, um, but then recognizing that you can get par uh, whether or not you've had treatment or not and what the ultimate sequela are so there's a whole discussion also around what we call adult ROP right or patients who. Had ROP regressed and then the peripheral changes that can occur. Um, So a couple of groups have shown that you can get par regardless of whether or not you had treatment, um, P Eric Noodleman and some folks and also, uh, the group out in, uh, in Taiwan with which you have shown some good data around uh the certain percentage of patients who get persistently vascular rena just through regressed disease. And what's interesting as we showed earlier, you're seeing more and more micropenis get uh get resuscitated and they get ROP. They also take longer. To resolve and you'll also get uh par in these cases and you just have to follow them. Uh, so in summary, uh, I think it's important to know the updated definitions of the international classification of ROP. Um, again, you know, not a lot of us do this, but for those of you who do screen, uh, making sure that we're documenting, um, in all the same way, you know, and it's interesting because in, in Roxana's talk about Oculomics, I think this is a really big discussion around data and documentation with HR systems because the Oculomic story is very, very dependent on consistent. And a harmonized unified data set, uh, so for a lot of us in the ROP space we're collaborating to create these common data sets so that we can understand certain things like respiratory distress syndrome or risk prediction models around systemic disease for many of these children, um, in terms of anti vaF treatment we're using it, OK, it's, it's common, but I think that you still need to have this sensibility around um specific patient. Uh, care issues around, uh, who's the right patient for antibif, what is reactivation, right? When do I treat with laser, so forth and so on, um, and I think like everything else, education is paramount, um, for making sure that people are trained to identify and manage the disease appropriately. uh, so with that, thank you, um, and look forward to discussing this. Published January 24, 2025 Created by Related Presenters Robison Chan, MBA, MD
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