Lecture: The ABCs of Proliferative Vitreoretinopathy (PVR)

SHIVANI REDDY: Great. Hello, everybody, good morning, good evening, good afternoon, wherever you’re tuning in for. I’m a surgeon at the Talley Eye Institute in the United States in private practice. It’s an honor to work with Cybersight and be with you here today. I thought let’s go to the belly of the beast, the one thing no one likes, which is proliferative vitreoretinopathy or PVR. So PVR really is a condition that humbles, you know, one of the best retina surgeons. They essentially — there is no really good treatment for this. The primary treatment is surgical. To understand PVR, we have to look at the pathophysiology and treatment modalities. You’ll see that the slides are very detailed, in case you guys want to go over these alert. We’ll be talking about all of these at an at the high level here. So let’s begin. First off, I have a question for everyone. How much experience do you have in the medical and surgical treatment of PVR? I’ll wait for your answers here. Okay. So there are some — good. So it looks like a wide variety of people kind of tuning in today. So, all right, we’re going to start at the basics here, okay? So first of all, what is PVR? So PVR essentially, think about it as an inflammatory process that is maladapted wound healing response in the retina, that goes rather excessive. So essentially it’s a series of complex cellular reaction that form fiber cellular membranes that eventually cause contraction. So with PVR, it’s the most common cause for failure of RRD repair. These membranes grow and contract on the vitreous in either side of the retina as well as the subretinal space and they also cause intraretinal fibrosis that can prevent the retina from flattening even after removing all the membranes so the contraction of these membranes leads to the reopening of treated breaks or creating new breaks in the retina or also causing macular distortion that leads to retinal detachments. Locally where you’re from, what would you say the local incidence of PVR is in your patient population? Okay. So we’re about the 5 to 20%, is what we’re saying, greater than 25%, wow, I wonder where that’s from. All right. So the other question is, in your experience, from what you guys have seen clinically, what is the most common cause of proliferative vitreoretinopathy? So 34% of you said standard retinal detachment and 39% standard vitreoretinopathies. So there’s a widespread scan. Genetically people are different, this is another big challenge with management and treatment. I just wanted to highlight that. The incidence reported in studies across the board is around 5 to 10% which seem to be the majority of what everyone was seeing. The incidence is largely unchanged in prospective studies over the past 25 years even though we’ve had a lot of revolution in surgeon techniques. Postoperatively, 77% of PVR appears one month after surgery and 95% appears within 45 days. This can vary based on patient population and surgeon experience. An atomic success after PVR RD surgery is anywhere from 45 to 85% and functional success defined as figures of 2800 or better is 26 to 67%, so it’s really not great, guys. There is a higher incidence with kids and there’s also a more rapid chorus in kids and young adults because they have hiring cellularity. Rates seem to be lower with intraocular foreign bodies injuries mostly because these patients are getting surgery earlier to remove the foreign body. What are the risk factors for PVR? Really there’s a whole bunch of risk factors here. Preoperatively, intro ocular inflammation is a big one. The qualities of the detachment themselves, so the number of breaks, the number of clock hours of the breaks, how large of an extent of an RD do you have. The pre-op, you know, PDR rates, grade A, grade B, early on. Also vitreous hemorrhage preoperatively, cutaneous detachment. Pigment release if you’re draining, or if there’s vitreous loss. Post operatively, persistent traction on breaks, all of these can lead to PVR. How does PVR form? That’s our question really here. So another poll for you guys. I just want to see what you think is necessary for PVR formation. RPE dispersion, blood ocular barrier changes, hemorrhage, or trauma. You guys tell me what you think. Okay, good. So most of you got this one. So, yes, it is a combination of A and B. So the two factors that plane to PVR forms the most are, number 1, dispersion of RPE cells and breakdown of the blood ocular barrier. So step 1, you have a retinal detachment, right? Once you have a retinal detachment you have RP migration onto the surface of the retina from underneath it. So what this does is it disrupts the outer blood retinal barrier. But also the inflammatory and ischemic cascade that happens after that is going to lead to the breakdown of the inner blood ocular barrier, that’s formed from the retinal capillary endothelial cells. You feel leakage of inflammatory material into your retina that was previously protected from all of that. So how does PVR form? We like to think of it as a nice, circular, linear process. And in some ways it is. But really, it’s not linear. All of the steps of PVR happen concurrently and really one step begets the other and each step potentiates the next step in the cycle. This is probably a more accurate schematic with double arrows going each way, showing how PVR is formed. First question to ask yourself is, why is vision limited to PVR, right? So go in, surgically repair the retina, reattach it, peel the membranes. Why can’t people see fell there are two reasons for this. The first is reactive gliosis. Muller cells regulate the microenvironment of the retina, right? So they go from the photoreceptors. In amphibians and fish they say morph into progenitor cells. It prevents further damage to the healthy cells while these cells are getting gliotic. It’s more cytokines and more growth factors causing further degeneration of these photoreceptor cells. So photoreceptor death — oh, sorry. So before we do that, reactive gliosis, really what’s happening here is the dying neuronal cell bodies in the retinal layers and their axons are replaced by these glial scars. As far as we know neurons should be able to regenerate. They can, but they don’t have any room to regenerate because the scar is obstructing the regeneration. The signal transmission between the layers is completely off. All of that is active gliosis. When your photoreceptors — when you have a retinal detachment and your photoreceptors start dying by day three, by day 28, probably greater than 50% die. We don’t know if they’re more protected in the actual eye or not but this is what we have for research. Apoptosis, you have ischemic retina is releasing a bunch of cytokines while these photoreceptors are dying from hypoxia and ischemia. You also have macrophages migrating into the subretinal space. All of this together is causing a lot of oxidative stress and it’s going to lead to further photoreceptor death, it’s just perpetuating on itself. Most of this migration happens three to four days in. If you repair it as soon as possible, a lot of these changes will stop and sometimes even reverse. It’s thought to traditionally occur in three phases, just like wound healing. There’s inflammatory phase, proliferation phase, and extracellular matrix remodeling phase, ECM. Not linear, everything is happening concurrently here. So the time frame is variable and it’s difficult to study in humans. Mostly it takes four to eight weeks to develop from the time of the retinal detachment. RPE cells are thought to be the largest cellular component. It’s made up of type of 4 collagen. That’s in their normal state. However during PVR formation, TNF alphas, factors like these are released by the circulating macrophages and these stimulate RPE stimulation, and favor adhesion. That’s what’s really happening here. TP53 levels in vitreous cells are downregulated by these inflammatory cytokines. TP53 actually encourages apoptosis. So if these are downregulated, now you have all these regulated cells that are very resistant to dying, they live longer. So that also perpetuates PVR. So extracellular matrix, we talked about that. Now we’re going to talk about EMT or epithelial mesenchymal transition. This is thought to be the biggest pathologic process in PVR. So essentially what this is, is RPE cells take on more of a mesenchymal property, they start to migrate and contract more. This is kind of facilitated by the matrix around these cells being cleaved by proteases that give a path for these RPE cells to migrate outwards. This is a schematic of what happened. Cell to cell adhesion keeps the cells together and the signals revels by that. First step is they lose their cell to cell adhesion. Once the tight junctions are gone, the RPE cells also lose their polarity. After that the shape changes and they start to migrate away from their basal lamina, essentially. They also take on more alpha smooth muscle axon compression. This is just a little review for you guys. Essentially there’s a bunch of blood borne components, a bunch of components from the macrophages themselves and from the differentiating cells. PDGF alpha receptors tend to be a very strong factor in kind of perpetuating the cycle, because they induce a bunch of downstream inflammatory effects and they cause formation which includes inflammation. So the cellular involvement, what kind of cells are involved? We kind of talked glial cells already. Hyalocytes are involved as well. They start to attract monocytes and macrophages and they also undergo differentiation and release pro inflammatory factors. Microglia is also upregulated in PVR. They’re found more in inflammatory PVR. We’ve already talked about the blood borne cells. There are also T lymphocytes and B lymphocytes. So essentially if you look at the PVR membrane, yes, you’re going to find a lot of fibroblasts but it was originally thought most of these were RPE cells. Now these can come from any of these cell lines, all of these cells have the ability to differentiate. Extracellular matrix remodeling is considered the culmination of the PVR process but once again, it’s happening from the start. The extracellular matrix is made up of collagens, proteins et cetera that allow scaffold formation for all these migrating cells. And that’s what eventually happens. It forms — these migrating cells essentially attach to this ECM scaffold. And because they’ve taken on these contractile properties, the membranes start contracting. They pull on the adjacent retina and that’s what causes the detachment. What are the PVR membranes actually made of? Early on they’re very cellular. But later on, it’s mostly collagen. And the contraction of these membranes actually decreases with time because they become less cellular. Are they true membranes? Not really, in the strictest sense. When we think of membranes we think of a single sheath, a very clear cleavage plane. PVR membranes are really incorporated with the neurosensory retina especially the inner layer. If you’re peeling PVR, if you watch us peel PVR you’ll see it’s very easy to tear the retina underneath, because they’re really integrated into the retina. Removing PVR membranes from damaged hypoxic retina is really a challenge. This is an interesting study that was done on eyes that underwent penetrating ocular trauma. So these eyes essentially, the penetrating ocular trauma created retinal detachments, patients came in with these retinal detachments, and they kind of graded the PVR based on how soon after their trauma did these patients come in. So when they divide them into different groups based on their presentation, patients around 21 days post trauma, you can see here that the retinas — I’m sorry. Before we go forward, what they did was they actually took samples of the PVR membranes themselves and samples the adjacent retina of these patients. At day 21, you can see the retinas are mostly cellular. And there’s not a lot of collagen fibers in this image C here, which is an actual histology of the membrane itself. As you go forward to about 30 days, you see that the retina is now losing its cellularity a little bit and you were neuronal degeneration here. You start to see blue collagen fibers deposit within the PVR membranes. Eyes operated on after day 50, we’re getting more folding of the retinal layers here, and by day 80, there’s a lot less actual retinal tissue here and more fibrocellular membrane. Between the arrows is where the retinal tissue is concentrated. This is a great histological representation of what’s happening during PVR. Vitreous cortical remnants are a big part of this. They’re considered a big factor in PVR formation. Vitreoschisis occurs when the anterior vitreous is left. Instead of being smooth like with a full vitreous separation. Removing vitreoschisis requires the use of triamcinolone. That was a summary of the pathophysiology. Now we’re moving on to classification. It was first described as massive vitreal retraction because it was thought to be more of a vitreous process. But it was shown there were cellular involvement with monkey models. That changed the name to massive periretinal proliferation. In 1983 the Retina Society classification updated this based on biomicroscopic findings. But it didn’t account for surgical difficulty. This classification underwent various iterations and in 1991, in was an updated classification which we use today. I have the classification tables for you guys here to go over later but I’m going to go over these stages here. So first we have grade A PVR, that’s really early PVR, right? So early PVR, you’re going to see not a lot of changes. The vitreous appears more hazy and then you’ll see pigment clumping. It’s very hard to show pigment clumping on photos but I picked this one because this patient came in about two months after detachment. You can see the retina is detached all the way through here. This is pigment on the anterior pigment behind his lens. Grade B is a little less subtle. What you see here is vessel tortuosity starts to occur. You have inner surface wrinkling, retinal stiffness which is hard to see clinically. The real giveaway is rolled edges around the tear. You can see the tear edges aren’t smooth, they’re like rolled outward. That’s a sign of grade B PVR formation. Another example of grade B PVR, this patient actually underwent retinal detachment repair. There is a very strong family history of retinal detachments in PVR. You can see light wrinkle formation here. A month later, this patient came in looking like this. The wrinkle formation was the early sign that PVR was brewing here. You can see the vessel tortuosity they’re talking about because of the pulling from the PVR membranes. Advanced PVR changes, you have at this point frank membrane formation and surface wrinkling which causes star fold. These are star folds that you see here. Also if there’s enough formation of — there’s enough PVR membrane formation, it can contract the retina, causing a funnel RD that can be closed or open. Funnel RDs, because they’re shaped like a funnel, form these courses multidirectionally. This is grade C, this is essentially divided into posterior and anterior. Posterior PVR can have full thickness folds circumferentially. These folds are still called star folds. You can have subretinal strands. Anterior PVR will cause anterior or posterior of the vitreous base, which will change the configuration of what happens to the retina. This is a case of diffuse posterior PVR. You can see star folds forming 360 degrees here. This is another case of a patient presented to me two months after detachment. And you can see a star fold formation down here, adjacent to his large tear. There’s also a star fold formation up here. This is a patient who presented to me with a six-month history of vision loss. This is what we would see in kind of final stages of PVR, the retina is all edematous, you can’t see details here. It’s kind of being pulled into a funnel configuration. Subretinal PVR can also occur, either in band configuration as we see here or in a napkin ring configuration around the disc which will pull the retinal tissue upward, difficult to remove, once again. Essentially the contraction pulls the retina out and forward towards itself in these situations. All right. So we’ve talked about the pathophysiology and classification. Now we’re going to talk about medical treatment. So let’s see here. Which of the following medical treatments are routinely employed in the management of PVR? Corticosteroids, methotrexate, anti-VEGF, antimetabolites, all of the above, none of the above. This was kind of a trick question. I just wanted to see where the audience’s head was at. I would say it’s a combination of all of the above and none of the above. None of these have been truly shown to equivocally work with PVR. The medical treatment of PVR is very difficult. There is no one clear pathway that we need to target, right? There’s no one clear inciting event. It’s a multilevel nonlinear process, as we talked about. The targets are typically either cell proliferation or inflammatory signal blockage. Ideally, whatever treatment we employ should be a combination of both. A bigger issue with this is, patients are presenting to us at different stages of PVR. So it’s not like every retinal detachment patient we see comes in at day one and we can say let’s block inflammation or they come in with later stage and we say okay, let’s block cell proliferation. We don’t quite know clinically where they are. A lot of this is patient history. A lot of times exam doesn’t reveal a lot either. It’s difficult to find a clear medical treatment for this. There are a ton of different medicines that are being studied for this. I’ll go over these at a very high level. I have tables summarizing the studies of all these medications. Essentially there’s no clear treatment winner at this point. So corticosteroids, of course this is a clear, very obvious target, right? Because corticosteroids are anti-inflammatory, antiproliferative. They do however, interestingly, have a dose dependent relationship. At low doses they stimulate proliferation in stern studies. At higher doses, they inhibit proliferation. Triamcinolone, Ozurdex, hasn’t been shown to have significant outcomes. Oral prednisone administration in patients with a primary RD that didn’t have clear PVR did have show reduced cellophane maculopathy down the line. There’s once again not a clear direction for this. 5-FU blocks DNA synthesis, it’s typically combined with low molecular weight heparin. There was some reduction in postop PVR in a study, prospective study done by Azaria et al. Other agents that are being studied as well, VIT100, and also daunorubicin. Vitamin A derivative inhibits cell proliferation. So there have been a couple of studies that have shown that it’s effective in modifying the course of PVR. Some studies have showing that it’s better in early PVR modification than late PVR modification. The problem with retinoic acid, it’s administered orally and there can be a lot of side effects from it but studies found a lot of these side effects are tolerable. In women of childbearing age, you have to be careful because this medicine can lead to birth defects. Once again, a summary slide of the studies here. Mitomycin C was found to be toxic at higher doses but found safe at doses of 2 micrograms at .1 ml. Hasn’t been clearly shown to improve outcomes. Methotrexate, this drug is causing a lot of excitement. It’s a folate analog. As retina surgeons we inject this a lot for intravitreal lymphoma. The inhibitory effects of it on cell proliferation are exciting. There have been a lot of studies done on methotrexate. Most recently the GUARD trial, we now have phase 3, part 1 results of the GUARD trial. And it’s shown that there are statistically significantly fewer retinal detachments within six months, about six months after RD repair. Methotrexate is given at time of surgery. Now, there are a lot of different doses of methotrexate being studied in various studies. I think there’s another large perspective trial in the works now, as soon as we get the results from that we’ll have more information. This is a schematic for you guys showing at what stages these medications and different medications will likely help with PVR, so good to go over when you get the slides later. What about anti-VEGF therapy? PVR is not considered to be an angiogenic process. VEGF is supposed to be super potent in downstream inflammatory and fibrocellular pathways in PVR. Another thing it does is downregulates TP53 which increases the longevity of these migrating contractile cells. If we can target that, hopefully the contraction stops. Studies with bevacizumab haven’t shown much difference. I think there’s trials going on with aflibercept. All these studies are kind of in their earlier phases. So once again, we need to — we’ll know more about these medications as the studies progress. This is just a little segue into our surgical discussion now. So this is a patient I showed earlier who presented with RD symptoms for two months preoperatively. He underwent a successful initial repair, peeling of the star folds, had a buckle done, ended up getting a retinectomy. He was under oil and we removed the oil and he’s doing fine. This is a sadder case, this is a patient here that came in with a two-month history hand motion VA. She underwent repair with a scleral buckle. She came in postop week 6 and this is what she looked like, large stretch holds and multiple star folds inferiorly. Now she’s under oil and we’ll see how she does. So now we’re going to talk about surgical treatment, the fun stuff. In the 1970s, surgeons said let’s cut these strands visible to us and use saline to push back the retina. That didn’t account for the role of RPE in PVR. Once we had vitrectomy, it allowed us to have more tools and target with minimum disruption. With the current methods, an atomic success rates are variable, anywhere from 60 to 80%. Functional success rates are from 40 to 80%. So when do you go in? This is the great debate, right? Look at the patient age. If they’re younger patients, they have a much more aggressive course. So go in earlier in these patients and remove that vitreous scaffold. If the macula is attached, please, please, please go in early, because you have a chance to save this patient’s vision. However, if a patient comes in, their PVR is more mature, their vision is already poor, waiting for those membranes to mature might facilitate better dissection of the membranes. Also if you intervene during active PVR it can create an additional stimulus or proliferation. There have been attempts to make predictive formulas as to who is going to develop PVR after RD surgery. Really they have poor positive predictive values. It necessitates future studies here. Clerical buckle. Long standing use of retinal detachment surgery. We perform these epi sclerally. They provide vitreous base support, they relieve anterior-posterior traction, they displace subretinal fluid away from the tear, they increase resistance to flow through the break so it’s harder for things to flow outwards through the break. And it reapproximates the retina to the vitreous. In mild PVR, it can be effective but if severe cases reattachment rate is pretty poor with just the buckle. What happens to the inferior vitreous base here? Essentially gravity pulls all those cytokines into the inferior vitreous. The inferior vitreous base is where you see the highest cellularity. What’s the solution here? Remove the base. But the problem is even with the most advanced surgical techniques, you cannot remove all of the vitreous space, it’s just too well-incorporated into the eye. It’s more protective against small breaks. We use a circumferential buckle which supports the base 360 degrees. We want a broad, high buckle and that’s what we need to relieve the traction in all directions. So, moving on to vitrectomy, what gauge vitrectomy do you guys routinely use? Okay. So 23 gauge, yep. So in the United States, I would say predominantly we’re either 23 or 25 gauge now. A lot of 25 gauge surgeons like to use 23 gauge for PVR because of the instrumentation and because of better access. But a lot of surgeons operate under 25 gauge routinely and sometimes even 27 gauge now. So what does vitrectomy do? Obviously Machemer brought about vitrectomy in 1971. It essentially removes transvitreal traction and allows membrane removal from the eye. So consequentially of course 20 gauge is used, it’s a great tool. But smaller gauge systems have been used with greater success and are gaining favor. So essentially what’s the advantage of smaller gauge systems? You have early vision rehabilitation because it causes less inflammatory changes in the eye. However there have been variable studies that have shown that smaller gauge systems, because of sutureless incisions or poor angle of trocar placement can lead to Hoyer rates of hypotony after. Do you have access to perfluorocarbon liquid at your surgical centers? Okay. So we’re divided. The reason I ask this is because PFO is essentially in a lot of cases of PVR, it’s become like a third hand for a surgeon, right? But it’s not used excessively in the United States either, mostly because it’s very expensive. A lot of the surgery done in the United States is done at surgical centers. So you have to be more thoughtful about cost, I would say, not so much in hospital systems, but in general, PFO is a very expensive productive to use. It’s — what is PFO? It’s the most common perfluorocarbon liquid used, essentially an inert heavy liquid that has really good optical clarity. And when in the eye, it displaces liquids with lower specific gravity such as blood, vitreous, and subretinal fluid and allows the breakage of those fluids. So it’s heavy, it sits on the retina, and it also stabilizes the retina when we need to peel because it provides some countertraction. Unfortunately it can cause histopathological changes in the retina so you have to be very careful. If you can, dissect away the posterior traction on the retina first before injecting PFO or there’s a very high chance it’s going to go subretinally. So we’re talking about peeling membranes now, right? Why do we people? We have to relieve traction. Do we peel ILM as well in addition to the membrane? Extending the ILM peel has been shown in a recent study that this allows for fewer redetachments at six months. They used PFO as an adjunct in some cases. Bimanual technique helps remove membranes. I have a couple of videos here using PFO, we’ll go over those in a second. Before we do, what instruments do we use in peeling PVR membranes? So we have diamond dusted membrane scrapers and flex loops that kind of gently lift the membranes off the surface of the retina, ILM as well. A retinal pick can gently lift up the PVR off the retina to create a dissection plane. And forceps are what are more commonly used. These have a flat base and are very strong and can peel dense membranes off. We also use ILF forceps. This is a patient who came in with kind of grade 1 PVR, had a bunch of vitreous pigment. So I thought that it would be a good idea to peel off his ILM in this case to remove the scaffold. As you can see here, there’s no PFO here. So it’s very important, when you’re peeling without PFO, is to peel towards the fovea first. Once you’ve cleared the fovea, you can start peeling circumferentially past the arcades as far as you can go. This video here, this next one, this is showing a peel with PFO in the eye. Here we have detached retina that’s been stained. PFO is being injected into the eye now. So inject the PFO for as far as you need the retina to flatten. If you’re trying to go beyond the arcades, go beyond the arcades. Kind of — it’s a good idea to kind of decide early on how much PFO you’re going to need in the eye. As you can see here a forcep is being used. As the ILM is being peeled along with the membranes, you can kind of see that we have to keep the forceps much closer to the retinal surface because we have that weight of the PFO overlying it. Your peeling direction is going to be different. When there’s PFO in the eye, he can typically peel posterior to anterior. Okay. So now we’re going to talk about another technique called vitreous wiping. So essentially this technique was described in 2019. And what this does is it removes any vitreal cortical remnants. You essentially take a small piece of PVA alcohol and use it to gently wipe away the remnants. That also has been potentially shown to decrease PVR formation after primary RDs. All right. Now we’re get to go to big guns here. Retinectomy and retinotomy. A four shortened retina does not flatten. You make a circumferential incision in the inferior retina here. It’s very important to keep the horns of the retinectomy above the horizontal meridian, or at least get the retinectomy edges onto your buckle. And the rules are greater than a 270 retinectomy is needed, better to complete a 360 retinectomy because we don’t want any retinal tags. Very important to remove the anterior retina that’s left over. This retina right here that’s left behind, because otherwise that will lead to near vascularization. Retinotomies can also be made so the retina is stretched out allowing for more flattening. You have to use PFO tamponade. I’m sorry, you have to use PFO in most cases to flatten the retina. And you have to use tamponade with C3F8 or silicone oil. You need a longer acting tamponade in these cases. This is a case of a retinotomy. This patient developed PDR that lifted. Diathermy is being used to mark the edges of the retinotomy — retinectomy, I’m sorry. The cutter is used to separate away the retina anteriorly from the edges of the retinectomy. People used to use scissors for this, but the 25 gauge cutter seems to do just fine. Here we’re removing the anterior retina remnants to prevent neo-vascularization and anterior loop PVR. Now we’re injecting perfluorooctane or PFO into the eye to force the subretinal fluid out. Once the retinectomy edges are flattened, laser is applied. It’s controversial as to whether to apply laser under PFO or not because the burns can potentially be hotter under PFO so you have to account for that with your laser power. And after this is completed, silicone oil is injected into the eye for a longer acting tamponade. This patient ended up doing quite well. And of course your trocar incisions are seen to be sutured if you inject silicone oil. This is another case, very quickly, of a patient who presented initially with visual acute of 20/20. There was an inferior RD here. They had a retinal detachment and a buckle. Postop week 6 you can see retinal folding starting. Week 10, there’s massive PVR with foreshortened retina. Her vision now is 2200. Postop week 2, these are the edges of the retinectomy and bleeding at the edges are quite common, this has to be managed, even then you can get bleeding and oozing like this. Here, postop month 1, the bleeding is decreasing, the scars are forming, the patient is under oil, doing quite well. Postop month 3, she develops this massive membrane. I peeled off the membrane. This is how her retina looked. Her vision is improved to 20/80, it doesn’t seem like a win, but in PVR world it’s definitely a win. So we’re going to finish up here with a few other components of PVR. Lensectomy, do a lensectomy if there’s a poor view or anterior PVR which can cause further contraction. If there’s not a lot of anterior PVR, try to save the anterior capsule with a cutter. And that also facilitates future IOL placement. Tamponades for PVR, essentially they’re used to — tamponades and retinal detachment surgery, essentially this prevents further fluid flow into the subretinal space until the scars mature. It can be done with air, gas, or oil. So longer acting tamponades like oil and C3F8 had better outcomes, better than SF6. But at six years, all of this evened out in patients who had macular reattachment at three years. The EVRS study didn’t show a difference in outcomes between oil and gas. Smaller studies show one is better than another. It’s really surgeon preference. Silicone oil, there are two different viscosities that we use, 1,000 cs or 5,000. In patients that have really bad PVR, have 360 retinectomies, usually 5,000 is placed and left in the eye because there is no thought of oil removal down the line. After oil removal, the rate of redetachment can be from 3.5 to 34%. So the pros of silicone oil, not a lot of head positioning requirements, the patient can see better, you can see better into the eye. There’s a lower chance of hypotony as well. The cons, you need to remove it surgically, it can emulsify and also causes deelevation. Another big thing we talk about but not as much is perisilicone proliferation. Silicone is concentrating everything into the inferior retina. If you do not have a retinectomy, you have a base that hasn’t been shaved well, this can be easy for future PVR formation. It’s called PVR soup, colloquially. Heavy silicone oil is used in some parts of the world. It sinks because it’s heavier than water. It seems to be a great adjunct in inferior attachments but studies show no an atomic differences in inferior PVR. Last but not least let’s talk about subretinal PVR. So subretinal PVR essentially is formation of subretinal bands, or the napkin ring configuration like we talked about, which that really needs a retinectomy to remove. You lift the retina off and peel off the tissue. In cases of bands like this, you can make punch retinotomies. Some people advocate to go right over the band to break the traction. Some people say don’t do this because if there’s still traction you can’t access the band. You can try whatever technique you like, you can use bimanual, you can use one hand and pull it at a tangential angle. Only remove them if they’re preventing retinal flattening, which two-thirds of subretinal bands don’t really need to be removed. This is just a case of a subretinal band patient. He came in, once again, with about two months history of a retinal detachment. That seems to be very common in our area of practice. He had a large subretinal band right there. I removed that with a punch retinotomy. He’s doing well, still reattached about a year later. All right. Last poll question of the day. Which of the following is the best technique for PVR management? There we go. Okay. So a majority of you guys voted, it depends on the situation, which was the whole point of my presentation, to show you guys that PVR is not a one-size-fits-all issue, right? So it all depends on the patient goals, how bad the patient was at presentation, do you need the expansion of the gas in the short term, or do you need the long term use of silicone oil, are you going to do a buckle or do you think you need to do a retinectomy based on the pre-op presentation. A lot of different factors go into this. That concludes the presentation here. So these are my citations. I wanted to thank Dr. Kitchens and Dr. Strand who helped me some of this and also Andy, Lawrence and the entire Cybersight crew, you guys have been amazing, it’s great to work with you guys, thank you. Questions? >> Thank you, Dr. Reddy. You can go ahead and stop your screen share, we have some open questions in the Q&A if you want to take a look. >> SHIVANI REDDY: Let me see here. What do you think about methotrexate and others to prevent PVR? Okay. So first question, when the retina is attached, it should be an anoxic. Yes, they die later, but remember, VEGF is also released by just from the bloodstream with the breakdown of the blood retinal barrier, so it’s not just from anoxic retina. The retina doesn’t start off anoxic, it’s still getting blood supply from the inner vasculature before that breaks down as well. Another question here, what do you think about methotrexate to prevent PVR. So in my clinical experience, it’s been very — it’s been great in preventing PVR in high risk patients. I actually use it per the GUARD study protocol in some of my patients I know either had earlier grade A or grade B PVR coming in. I try to peel the membrane in these patients and then do I GUARD study protocol on these patients in terms of injections, which is — sometimes I can do an injection at the time of surgery, sometimes not, but I try to do the eight weekly shots followed by four monthly shots in these patients. What are the top two treatment standards for PVR for meta-analysis to be done on this subject? Really I would say in the U.S., the top two treatments are methotrexate and oral retinoic acid, those are the ones most well-studied. How to avoid PVR in children undergoing RD surgery? That’s a very complicated question. I don’t think you really truly can avoid it. But I think it’s just — you know, children are a whole different beast. So that will be more of a pediatric retina surgery presentation that we can talk about. But there’s not a really good way to prevent PVR in children, just because of the — just because of how cellular these children are, how robust their immune systems are. Are there genetic factors that predispose to PVR. I’m sure there are, because in practice, most retina surgeons will tell you, we have patients who come in that have been detached for six months that have completely, you know — have retina that’s completely pliable, lays down perfectly well, does not redetach. We have patients who have been detached for less than a week that have early PVR. So there are genetic factors. And I think there are a lot of studies going on on this, but we don’t have, once again, a clear answer yet. Any benefit of staining membranes with brilliant blue versus ICG? So this is an interesting question. So ICG is not technically FDA-approved in the states for peeling. So brilliant blue is really the first FDA-approved stain that we can use in treatment, although ICG is the most popular. I think that brilliant blue is likely safer than ICG because ICG can cause phototoxicity. The staining capabilities of it are quite high, and a lot of what we use in retina surgery is based on the your training preference. I trained with both, so I use both. With brilliant blue I tend to use that more if I see a lot of traction, there’s a higher chance of migration subretinally when I inject the dye. Otherwise I use ICG as a standard. Okay. So would you please suggest some perioperative tips to avoid postop PVR. The most important thing that I in my experience think you can do to avoid postop PVR is remove as much of your vitreous as possible, because the vitreous is what really causes the scaffold, the inferior vitreous really — the base of the vitreous allows for scaffold formation essentially for these PVR membranes. The more vitreous you can successfully remove, the better off you can be. Peeling the ILM in the macula seems to be more protective for positive operative macular PVR. That’s what we’re trying to prevent here. If we can get the macula to reattach and sit flat, patients tend to do pretty well here. In your experience after RD, how much time does a patient have to restore vision? Once again, very variable. I wish I had a great answer for this. It depends on the patient. It depends on your patient population. I’ve seen patients — the conventional wisdom is try to reattach that patient as quickly as possible because you want to prevent photoreceptor death, you want to prevent all these anoxic effects. But essentially we don’t really know who is going to have a great visual outcome and who is not, because we don’t know who is getting this reactive gliosis. That’s why we try to say as a rule, since we don’t know who’s going to have these downstream inflammatory effects, let’s repair everyone as if they’re a PVR candidate, which means as quickly as possible. As quickly as you can get them into the OR, I would say try to restore their vision. Do you use any PVR membranes? In my experience, I use ICG ILM. PVR membranes are more of a negative staining. Sometimes triamcinolone can highlight them. But it’s more of a negative staining effect similar to an ERM, you know it’s there based on movement and how the retina is moving when you’re peeling them. All right. Any other questions here? Vitreous is removed during vitrectomy, why does PVR develop? Great question. That’s, once again, we’re coming back to it, number one, there can be vitreoschisis, you think you have a PVR, but there’s a layer that’s formed on the surface, or you just have done an incomplete vitrectomy peripherally, so you really have to be careful. Either you shave very, very well to the vitreous base, right, and try to decompress that vitreous base as much as possible, or you put a scleral buckle that is very high and — not very high, but, you know, moderately high and posterior to provide kind of countertraction to any membrane formation. After three years, do you try to fix PVR? Yes. I try to fix any retinal detachment that appears on my doorstep if possible. At the very least, it’s because if these eyes start to develop anterior PVR, they can basically become very hypotonus. So I will try. All right, guys. Does methotrexate enhance PVR in tumor-bearing women. That’s a great question, Boris, I don’t know the answer but I can do research and get back to you on it. All right. I think we’re pretty much done. >> Perfect, thank you, Dr. Reddy, I think we can stop here. >> SHIVANI REDDY: Okay, great. >> Thank you again for your time today. >> SHIVANI REDDY: Thank you. Take care, guys, thank you.