During this live webinar, we will go over the classification and management of diabetic retinopathy. Clinical cases will also be presented for review.
Lecturer: Dr. James Lin, Vitreoretinal Consultants of New York, United States
DR LIN: All right. Hello, everyone. Let me pull up my presentation. So my name is James Lin. I’m practicing at the Vitreoretinal Consultants of New York, and today I’ll be talking about diabetic retinopathy: An overview. So there’s a couple of objectives in my talk this morning. I’m gonna be first starting out with epidemiology and risk factors for the disease. Then I’ll be talking about pathogenesis, followed by clinical findings and classification, and then screening and management, along with some pivotal clinical trials for diabetic retinopathy. And then wrap up with some case examples. So first starting out, epidemiology. So about a third of the global population of people with diabetes are expected to have diabetic retinopathy. It’s a primary cause of blindness in adults age 20 to 74 years old. At least, here in the US. And one of the first studies, called the Wisconsin Epidemiological Study of Diabetic Retinopathy, found that there was actually a direct association of increased prevalence of diabetic retinopathy with a longer duration of diabetes. So essentially, if you look at type I and type II diabetics, here in this graph below, you can see that it makes sense that the longer amount of time that they have diabetes, the higher the prevalence that they have of diabetic retinopathy. So moving on to risk factors, one of the major risk factors for diabetic retinopathy is hypertension. So one of the original pivotal trials, called the UKPDS, actually looked at type II diabetics and randomized them to tight blood pressure control, as defined as less than 150/85 or less tight blood pressure control, defined as less than 180/105. They found that patients with the tight control had a 34% reduction in risk of worsening retinopathy and 47% reduction in the risk of losing three lines of visual acuity. As we all know, glucose control is a major modifiable risk factor for diabetic retinopathy. And the same study, the UKPDS, again, looking at type II diabetics, found that — they randomized patients into a dietary control group or a drug therapy group. And the dietary control group actually had a hemoglobin A1C of 7.9%, whereas the drug therapy group had a hemoglobin A1C of 7%. And they found that the drug therapy group had a decreased risk of retinopathy. Now, a similar study, but looking at type I diabetics, this is a DCCT trial. It randomized patients to tight control or standard control. With tight control being a hemoglobin A1C of 7.5%, and a standard control of hemoglobin A1C of 9.5%. And they found really no difference at first within the first two years. But then after that, the tight control group actually had a decreased progression. So it found that basically with tighter control of A1C, type I diabetics tended to have a lower prevalence of retinopathy. Additional risk factors include dyslipidemia and nephropathy, and pathogenesis of retinopathy is that hyperglycemia leads to endothelial cell damage and pericyte loss, which eventually leads to capillary occlusion and retinal non-perfusion. There are three ways that vision loss occurs. First is with macula ischemia, because of capillary occlusion, secondly, macular edema secondary to capillary leakage, and finally sequelae of neovascularization, secondary to retinal ischemia. These are just a list of your typical retinal findings in diabetic retinopathy. I’ll go through each one of them. So first you have microaneurysms, which are localized saccular outpouchings of the capillary wall. They’re seen generally in relation to areas of capillary non-perfusion, and they may leak, because of the breakdown of the blood-retinal barrier. Or they can thrombose. So this is a fluorescein — down at the bottom, on the left hand side, you can see that the microaneurysms will have this very characteristic focal leakage pattern. On the fluorescein. Which you can see in many diabetics with retinopathy. And then in another finding, of course, hemorrhages. So there’s two types of intraretinal hemorrhages. There’s a dot blot hemorrhage, which arises from the venous end of the capillaries. And they’re usually located in the middle layers of the retina. So typically in the outer plexiform layer. Then you have your name hemorrhages, which are more superficial hemorrhages. They arise from the superficial precapillary arterioles, and they’re typically found in the nerve fiber layer. You can also have hard exudates, which are lipid deposits associated with lipoprotein leakage from microaneurysms in capillaries, and they can accompany retinal edema. They’re often actually seen at the junction of normal and edematous retina. There’s also venous beading, which is a preproliferative finding, which is an irregular constriction and dilation of venules. And these are often called venous loops as well. And then you can also see intraretinal microvascular abnormalities, or more commonly referred to as IRMA. These are also preproliferative findings, that essentially are arteriole to venule shunts, and are often seen adjacent to areas of capillary closure. So one of the similar findings to IRMA are — neovascularization. And one way to kind of tell them apart is, first of all, IRMA usually doesn’t — a major thing is that they don’t grow into the vitreous cortex. So they don’t really have the ability to cause tractional fibrovascular proliferation, and on angiography, they don’t leak like neovascularization does. And a key point is that IRMA is pre-proliferative. So diabetic macular edema or DME is when fluid initially accumulates between the outer flex form and inner nuclear layers. Eventually the entire thickness of the retina can become edematous. This can be accompanied by subretinal fluid as well. On the right hand side, you see the fluorescein findings of macular edema with hyperfluorescent leakage in the macula. This is sort of a characteristic finding that you see. And then another finding is macular ischemia. In the past, fluorescein angiography is a good way to evaluate for macular ischemia, because you can see the enlargement of the foveal avascular zone, as you see in the picture on the right hand side. But I wanted to show you an OCTA picture particularly on the left, because OCTA can be a useful tool in looking at vascular abnormalities. And in particular, macular capillary non-perfusion with enlargement of the foveal avascular zone can be seen with worsening diabetic retinopathy severity level. So in this photo, you can see that there’s actually reduced capillary perfusion density in a patient with proliferative diabetic retinopathy. Then you have — as the retinopathy progresses, it leads to neovascularization.
This is essentially new vessel growth mediated by multiple factors, including VEGF as a main one. And new vessels can start as endothelial proliferations. And these usually arise most frequently from the veins. And they grow into the potential plane between the retina and the posterior vitreous cortex. And the vitreous actually serves as a scaffold for these vessels. And because these vessels are abnormal, they can develop into subhyaloid hemorrhages. Vitreous hemorrhages. And ultimately they can form fibrovascular membranes and tractional retinal detachment. So here’s a fundus photo showing the optic nerve with neovascularization of the disc. And this is a fundus photo on the left, showing a patient treated with PRP. And there’s this area that looks like there could be neovascularization there. And then on the fluorescein, it’s actually confirmed by the pattern of leakage. And then finally, you can have fibrovascular membrane and tractional retinal detachment. Which is the end stage of this disease process. So now I’ll go a little bit into classifications. So NPDR is classified as mild, moderate, or severe. PDR, or proliferative diabetic retinopathy, is defined as early or high risk. And then DME, now with OCT, we see commonly especially in the studies that are looking at DME, they’re either classified as center-involving or non-center-involving DME. But before I go a little bit more into the classification, I wanted to talk about screening. So generally speaking, for type I diabetics, the recommended time of first screening is five years after diagnosis. And if they have minimal — they don’t really have any particular findings of retinopathy, or minimum findings, they can be screened annually. But that’s the minimum. So annually is a minimum follow-up time. In type II diabetics, they’re recommended to be screened upon their diagnosis. And then annually as a minimum follow-up interval. And in type I or type II diabetes, in the setting of pregnancy, these patients are recommended to be screened soon after conception and early in the first trimester. And then if they don’t have any retinopathy or mild to moderate NPDR, they’re recommended to be screened every 3 to 12 months. And then if they have severe NPDR or worse, then they are screened every 1 to 3 months. This is kind of a busy table. Essentially showing the follow-up guidelines for patients with retinopathy. So I wanted to draw attention first to the presence of center-involving diabetic macular edema. So regardless of the severity of the retinopathy, if they have center-involving DME, these patients should essentially be screened at one month intervals. Now, if they don’t have any DME at all, then if they have normal or minimal NPDR, or if they have mild NPDR, they can be screened at about a year’s time. If they have moderate NPDR, they can be screened at 6 to 12 months again. And then if they have severe NPDR, they can be screened at 4-month follow-up interval. And the same holds true for this 4-month follow-up interval for non-high risk PDR and high risk PDR. And then if they have inactive PDR, they can be screened at 6 to 12 month intervals. Now, if there is DME, and it’s non-center involving, then the follow-up guidelines are somewhere in between. As you can see in these follow-up interval months in the table. So now moving back to classifications. So I mentioned earlier that there is mild or moderate NPDR, before you hit severe NPDR. So mild NPDR is usually classified as eyes that really only have microaneurysms. And then moderate NPDR is seen as anything that’s in between mild and then severe, which I’ll go over just in a moment. And then severe NPDR is classified by the 4:2:1 rule, as defined in the ETDRS trial. And the 4:2:1 rule means the following. So they have to have severe intraretinal hemorrhages and microaneurysms in 4 quadrants. Or venous beading in two or more quadrants. Or moderate IRMA in one or more quadrants. So if patients have severe NPDR, you really have to be careful. Because they have about a 15% risk at one year and a 60% risk at two years of developing proliferative diabetic retinopathy. So these patients need to be monitored and screened pretty carefully. And I just mentioned before the ETDRS trial. So what exactly did the ETDRS trial look at? One of their main endpoints was looking at the macular edema, treatment of macular edema. With focal laser. And they found that with focal laser, it decreased the risk of moderate vision loss. It also increased the chance of moderate vision gain. And focal photocoagulation also reduced thickening of the retina in DME. They also looked at early scatter photocoagulation and found that early scatter actually resulted in a small reduction in the risk of severe vision loss, but it wasn’t indicated for eyes with mild to moderate retinopathy. And it may be the most effective in patients with type II diabetes. And finally, they took a look at the utility of aspirin. So they found that aspirin didn’t alter the progression of diabetic retinopathy. It did not increase the risk of vitreous hemorrhage. And it did not affect the visual acuity. However, on the flip side, it did, as we know, reduce the risk of cardiovascular morbidity and mortality. So now moving on to treatment of NPDR — so other than systemic control, there aren’t really any current clear treatment guidelines. You may consider PRP for patients with severe NPDR. And there really, at this time, isn’t a clear role for surgery in NPDR. And ranibizumab and aflibercept are agents approved for NPDR without DME. One question that we’re asking — we’ve been asking, ask we’re still trying to understand sort of long-term data is: Should we even be using anti-VEGF for patients with NPDR? So two trials that sought to understand this better were the recently published PANORAMA and Protocol W trials. And they found that treatment with aflibercept resulted in reduction of PDR and center-involving DME. But unfortunately it didn’t translate into better visual acuity. So this is something that — this gives us more information that perhaps treating patients with NPDR with anti-VEGF — there is some utility, but I think it gives more room for discussion. And ultimately, we need to see what the long-term data is. Because this is the data at two years. So PDR is a more advanced form. So this is proliferative diabetic retinopathy. And high risk PDR is important to know that definition. So what does that mean? So high risk PDR is classified as any NVD with vitreous or preretinal hemorrhage. It’s also characterized — also defined as NVD greater than a quarter disc area, with or without vitreous or preretinal hemorrhage. Or NVE greater than or equal to half a disc area with vitreous or preretinal hemorrhage. Usually if patients develop high risk PDR, treatment is considered mandatory. So what does treatment… What are treatment options? So PRP is the classic option. And like I mentioned, the high risk PDR was defined in the DRS trial. And the reason why we treat high risk PDR is because eyes treated with PRP in this trial had a reduction of greater than 50% in rates of severe vision loss, compared to untreated eyes. And those with the greatest benefit were the high risk PDR eyes. Now, while the risks are minimal, some of the potential risks of PRP are the following: Choroidal detachment, decreased peripheral vision, pupillary dilation, loss of accommodation, and loss of corneal sensitivity. Now, over the past couple years, anti-VEGF definitely has become very, very popular in the treatment of PDR. Because it leads to rapid regression of neovascularization. But some complications that can occur include inducement of or worsening of tractional retinal detachment with the crunch phenomenon, also retinal tears, as well as combined tractional rhegmatogenous retinal detachments. So one of the really pivotal trials in the treatment of PDR has been Protocol S. So this is something that really should be committed to memory. Because this looked at ranibizumab versus PRP. And at the five-year mark, the visual outcomes were essentially equivalent between the two groups. And this really is helpful, because it gives clinicians the option of using PRP or anti-VEGF for the treatment of PDR. Or in many cases, patients are receiving a combination of both. And so it allows a clinician the ability to treat based on individual patient circumstances. Now moving on to surgical management of PDR. So indications for vitrectomy are as follows. These are just general indications. So non-clearing vitreous hemorrhage, significant recurring vitreous hemorrhage, dense premacular subhyaloid hemorrhage, tractional retinal detachment involving or threatening the macula. Combined tractional/rhegmatogenous retinal detachment. Red blood cell or ghost cell glaucoma, and anterior segment neovascularization with media opacities preventing PRP. Now, common indication for surgical management is vitreous hemorrhage. So the DRVS trial actually looked at the role of early vitrectomy in severe PDR. And it found that in type I diabetics, with severe vitreous hemorrhage, they actually benefited from early vitrectomy. And nowadays, with the advent of small gauge vitrectomy, with the technology that we have, performing — I think there’s been more of a shift towards, in some cases, earlier vitrectomy. Because of the relative safety and advances of technology. And then of course for tractional retinal detachment, this is an indication for surgery. And although tractional detachments that don’t involve the macula can remain stable and can be observed, when the macula becomes involved or threatened, then prompt vitrectomy is recommended. And of course, urgent surgery is recommended for combined tractional and rhegmatogenous detachments. So I spoke earlier. I mentioned something about the OCT-based classification of macular edema. This is defined as either center-involving or non-center-involving. And is a newer classification, as opposed to the early ETDRS criteria that established the definition of CSME. Or clinically significant macular edema. And this was an indication in that trial for focal laser. So you can’t get away from this lecture without knowing what… Without talking about what CSME means. So traditionally, CSME has been defined as one of the following. So thickening at or within 500 microns of the center of the fovea. Hard exudates at or within 500 microns of the center of the adjacent retina, thickened with edema. Or thickening one disc area or larger, if within one disc diameter of the center of the fovea. So moving on to treatment of DME, so treatment is typically indicated if it is center-involving and affects the visual acuity. It’s preferable to initiate DME treatment before scatter laser and even prior to cataract surgery, if possible. And one important trial that I’m gonna talk about, that I’m gonna mention, is the protocol V trial. So this actually found that eyes with center-involving DME and visual acuity greater than or equal to 20/25, they could be observed with close follow-up. Because visual outcomes were not compromised at the two-year mark. So in these patients, I often have a discussion with the patient, whether or not they want to pursue treatment, or in some of these cases, it’s reasonable to observe. But they need to be closely monitored. So anti-VEGF is now the mainstay of treatment. There are three options. There’s bevacizumab, ranibizumab, and aflibercept. Faricimab is a new agent that’s coming soon. It’s been just approved, at least here in the US, just recently. And it actually targets VEGF and angiopoietin 2. So we’ll have to see how this fares. In the treatment of diabetic macular edema. But this is something that’s pretty exciting that’s coming out on the market. So I mentioned anti-VEGF as a mainstay of treatment for DME.. So this is kind of a busy table that shows some of the pivotal trials in the study of anti-VEGF for the treatment of DME. So protocol I looked at ranibizumab plus prompt or deferred laser versus laser alone. Or in combination with steroid. And it found that anti-VEGF provides superior visual acuity compared to laser, plus or minus steroid. And then adding focal or grid laser at the initiation of anti-VEGF is no better. And possibly worse for vision outcomes than deferring laser treatment for 24 weeks or more. The RISE and RIDE trial looked at ranibizumab versus sham. And this was a pivotal trial that demonstrated the efficacy of ranibizumab in improving vision with patients that had DME. And the similar finding was seen in VIVID and VISTA, but this looked at aflibercept. So it found that aflibercept was very efficacious. In improving vision. And then protocol T is also important to know, because it actually looked at all three anti-VEGF agents, and found that aflibercept was superior than bevacizumab and ranibizumab in eyes with worse baseline vision. As defined as less than or equal to 20/50 vision. At the one year mark. And then at two years, aflibercept was no longer superior to ranibizumab. It also found that all three agents were equivalent in mild baseline visual impairment, as defined as 20/32 vision to 20/40 vision at baseline. Another option that we have in our treatment armamentarium for DME is steroids. So traditionally, triamcinolone has been used. But I’m just gonna mention the two implants that are available. There’s a fluocinolone insert and dexamethasone implant that are good treatment options for DME. And this is a table just listing out some of the major protocols and studies, looking at the role of steroids in the treatment of DME. So protocol B looked at focal and grid versus versus intravitreal triamcinolone. It found focal and grid more effective at two years. Protocol I looked at intravitreal triamcinolone plus laser versus ranibizumab plus or minus laser alone. And found that at 2 years, triamcinolone plus laser was inferior to ranibizumab plus or minus laser and to laser alone. And protocol U was interesting, because it looked at combo therapy. Ranibizumab plus dexamethasone versus ranibizumab alone, and at the six month mark, it found that eyes in the combination group did not have superior visual gains, compared to anti-VEGF alone. But they did have improved retinal thickening on OCT. And of course, DME traditionally has, based on the ETDRS, as I mentioned before, it found that focal and grid laser is of course a reasonable option for treatment of DME, especially if there’s a clear area of focal leakage on fluorescein. So this is still a reasonable option in select patients. And then of course, pars plana vitrectomy has been studied as a potential treatment for macular edema. One of the protocols in this study is protocol D, which found that retinal thickening was reduced after vitrectomy, but the median visual acuity remained unchanged at 6 months. So ultimately, we need more studies to determine the role of vitrectomy in treatment of DME. So this is… A lot of it is kind of to be determined. So finally, I’m gonna go over some case examples, to demonstrate some imaging and treatment of diabetic retinopathy. So this is my first example. It’s a 53-year-old male that presented with severe NPDR and DME in the right eye. Visual acuity at baseline was 20/70. With DME. And then he was treated with aflibercept. So after one injection of aflibercept, the visual acuity improved to 20/60, and there is some improvement of the macular edema. After four monthly injections, you can see visual acuity improved to 2020, with almost complete resolution of the macular edema. But unfortunately, like a lot of diabetic retinopathy patients, diabetic patients in general, they’re lost to follow-up. And the patient returned 9 months later with worsening of edema, but visual acuity stayed steady at 20/25, more or less. So in this case, it was chosen to observe this patient because of the good visual acuity. This is the second example. This is a patient that presented with a history of moderate NPDR. And on exam, you can see on these fundus photos — it’s really not too much to see. There’s some scattered dot blot hemorrhages in probably four quadrants or so. So I would say at most… There’s some sclerotic vessels in the periphery. I would say maybe at most this is a patient with severe NPDR. But then you get the fluorescein. And that tells you a very different story. So this patient had multiple areas of neovascularization. Elsewhere. In both eyes. And also, really significant capillary non-perfusion in the periphery as well. So this patient actually underwent PRP in both eyes. So from here on out, the last couple of examples I have actually… I’ll be showing some photos of OCTA. And just kind of showing it as a useful tool in imaging patients with diabetic — particularly proliferative diabetic retinopathy. So this is a 36-year-old male with a history of proliferative diabetic retinopathy. Visual acuity is 2020. The fundus photo of the right eye shows peripheral laser scars. He had PRP done, with really no clear evidence, no overt evidence of neovascularization. Then you get the OCTA. And on the superficial retinal slab, you can see that there actually still are areas of neovascularization elsewhere. This is another example, demonstrating the utility of OCTA as an adjunct for looking at diabetic retinopathy. So this is a 51-year-old male with a history of type1 diabetes. Presented after PRP for PDR. Visual acuity is 20/15. Dilated exam of the right eye shows peripheral laser scars, as you can see in the fundus photo. With really no evidence of neovascularization. But then you get the OCTA. And lo and behold, if you look at the RPE-Bruch’s slab, there’s this area here showing choroidal neovascularization that’s actually associated with the history of the PRP laser. And this example is a 58-year-old male with type II diabetes. Visual acuity is 2040. Fluorescein angiography of the right eye shows areas of peripheral hyperfluorescence. That’s consistent with leakage from neovascularization. And just kind of demonstrating the utility of OCTA as another way to image neovascularization, the image on the right shows that the OCTA also reveals neovascularization in the same exact area as seen on fluorescein angiography. So really, it kind of… The point I’m trying to make is that OCTA, if available, I realize that not everyone has OCTA available. But it’s useful in the sense that it’s… You know, it’s non-invasive. It’s pretty quick. And you can really see in detail areas of ischemia and also exactly in which layer of the retina that the neovascularization is located. And this example is a 41-year-old male with type II diabetes, presenting with proliferative diabetic retinopathy. Visual acuity is 2020. Fundus photo of optic nerve shows neovascularization, as seen in image A on the left. OCTA shows dramatic neovascularization of the disc in the same eye. So it’s really quite impressive, how much neovascularization there is, that you can’t really appreciate as well, just by looking at the fundus photo. And then the patient was then treated with panretinal photocoagulation and anti-VEGF therapy, with progression of neovascularization in the disc. As you can see in image C. But however, OCTA showed some regression, but there’s still some persistence of neovascularization of the disc. So the point I’m trying to make here is that just like in some of the other examples, it’s easy to be fooled into thinking that a patient doesn’t have very severe retinopathy. Or they may not even have proliferative retinopathy. But then there really is a role for looking at fluorescein angiography and OCTA and really helping you determine if a patient — the true extent or true severity of a patient’s disease. And so thank you for listening. Just wanted to acknowledge Dr. Harry Flynn for providing some of the images that I used in this presentation. Thank you all for listening. I’ll take some questions. If you guys have some. So let’s see. Let me try to answer some of these questions. So… First question I see here: Diabetic retinopathy doesn’t progress sectorally. Why do we classify it based on sectoral involvement? So… Sectoral… I think that… You know, traditionally, looking at the diabetes severity level, you know, the ETDRS was all based on severity level, based on fundus photos. So I think when they first kind of looked at the… When they were looking at classifying diabetic retinopathy, they probably… They probably found a correlation between looking at how much degrees or how much sectoral involvement there was, and how quickly the diabetes was — the retinopathy was going to progress. So even though it doesn’t progress sectorally, per se, based on the initial kind of old studies, the ETDRS trial, we’re kind of using these quote-unquote “sectoral” or sort of quadrantic findings or severity of findings to classify its involvement. So I hope that answers the question. Is there any studies that showed superiority of yellow laser compared to green laser for macular edema? Not that I know of. I usually just treat with whatever laser I have available. I don’t think that… I would have to really look at the old studies, to look at… They might have used… I think they might have used yellow laser. But I would have to really look at the original study and get back to you regarding that. In young patients with type I diabetes, we commonly observe faster progression of diabetic retinopathy. Are there any differences in the disease classification and follow-up period? So generally, after their first follow-up, type II and type I diabetes — their follow-up intervals should be the same. It’s just based on the severity of their retinopathy. But there also isn’t really a difference in the disease classification. But I will say that in young patients with type I diabetes, I know that because they progress faster, I’m usually much, much more aggressive in their treatment. In a patient with NPDR and center-involving macular edema, will the edema be resolved with just tight glycemic control? I would say yes. It’s definitely possible that even in patients that you see with center-involving macular edema, sometimes they really have no visual complaints. If their vision is good. I mean being if it’s 20/25 or better, like I mentioned… Usually I choose to observe some of these patients. And I’ve found that tight glycemic control can help to resolve the edema. But it’s not like if they resolve the… If their glucose control is quickly controlled, it doesn’t mean that the edema is going to resolve in a linear pattern. Sometimes there’s a pretty big delay in the improvement in the severity of the retinopathy. So short answer is that: Yes, with tight glycemic control, the edema should improve. Is there any chance of NPDR stage regression with systemic control only? Yes. Like I mentioned before. Yeah. Sometimes if they are just systemically controlled, their NPDR does get better. Do you recommend any antilipid medications for NPDR? I don’t usually. I just tell patients that they really need to get their glucose under control. The glucose, blood pressure, all those risk factors under control. Any thoughts on… I’m assuming that this is brolucizumab? Correct me if I’m wrong. But it was not approved for diabetic macular edema. So usually we don’t use that. What is your first option in case of high risk PDR — anti-VEGF or PRP? So it really depends on if there’s a presence of diabetic macular edema. Usually if there isn’t any macular edema, then I’ll go straight to PRP. And… Or if there isn’t any edema and they have some vitreous hemorrhage, that doesn’t really give me a good view for PRP, then I’ll start out with anti-VEGF, followed by PRP, as the view allows. And then if there is diabetic macular edema, I generally will start treatment with anti-VEGF, followed by PRP soon after. Protocol V, visual acuity greater than 20/25, is mentioned… Patients only need close follow-up. What exactly do we monitor? Essentially you monitor the edema. Usually these patients I’ll follow up in one to two months, if they have good visual acuity with center-involving DME. So I follow them with OCT. Do you use OCT biomarkers in deciding/modifying your treatment? If so, which ones are significant? Usually I don’t. I mean, if you’re talking about biomarkers as in certain findings on the OCT, you know, there’s some information out, talking about the presence of DRIL, or some OCT findings that show that patients will have a worse… If there’s atrophy of the inner retina, which is basically what DRIL is, and usually if this is in the context of the history of longstanding…
Macular edema, then we know that the prognosis — their visual outcome is not as good. But I don’t really modify… I don’t usually modify my treatment based on any particular biomarker. Do you recommend early vitrectomy in high risk PDR? This is really a really good discussion topic. I generally don’t. That’s just… My practice pattern. I usually will do whatever I can with anti-VEGF and PRP, as the view allows. And then there are still some people that really advocate for early vitrectomy in high risk PDR. And I think that’s a very reasonable option as well. So I think people will fall along different ends of the spectrum. But either way is reasonable. Which case of DME do you prefer to inject intravitreal steroid too? I usually don’t. I usually… Yeah. I’ll use steroids if patients have recalcitrant edema. I think that just because the… Especially in phakic patients, or the risk of glaucoma… Even though it’s low, I think that it gives me a little bit of pause, before I go straight to steroids. But some patients really… They don’t respond with anti-VEGF. Some of these patients respond really well to steroids. So that’s really a good option in certain patients. For certain patients. With DME. When a patient has cataract and DME, how do you manage in this case? And is one injection anti-VEGF enough before surgery? Generally… There’s no clear guidelines on this. This is, again, sort of… It’s open to discussion. But generally speaking, in these patients, I do get started with anti-VEGF before I have them go for cataract surgery. And generally speaking, I like to see some sort of response with my treatment, before I let them… Before I pass them back to the cataract surgeon. So as long as… The basic thing is… As long as they’re being treated during… Preoperatively, before their cataract surgery and I see them afterwards, to see if the edema has worsened, so I can treat them in time, postoperatively, then I’m generally okay with that. Do you inject anti-VEGF in the case of center-involving DME? So yeah. I usually will discuss with the patient. I would say that the data is out that… We can observe these without long-term detriment to visual outcomes. But oftentimes, I would say… If they have really… If they have very good visual acuity, I choose to observe them. But I monitor them closely. In which case of diabetic retinopathy do you recommend anti-VEGF at the end of cataract surgery? I usually don’t inject anti-VEGF at the end of cataract surgery. But that’s because I don’t do the cataract surgery. So I think that in other practice patterns, or other practice settings, injecting anti-VEGF at the end of cataract surgery is fine. And is another way to maintain control over the DME. This is asking — not specifically DME, but yeah. In the case of just generally diabetic retinopathy, I don’t really have strong feelings for injecting anti-VEGF at the end of cataract surgery. But for DME, I think that’s an option. But like I mentioned before, I usually will inject them preoperatively, and let them go for the cataract surgery and continue treatment with anti-VEGF after their cataract surgery. In severe NPDR patients, in what conditions should we offer PRP? I would say… I alluded to this before, but I feel like a lot of diabetic patients are notoriously bad at following up, because they don’t really notice that their vision is bad until it gets really bad. So in severe NPDR patients, I would say that if I have a feeling… Obviously you can’t predict, always. But if I have a feeling that patients are really not gonna follow up, especially if it’s a young person, then I would probably have a lower threshold for offering PRP. If a patient has macular edema and good vision, should we observe or treat to keep the good vision? I answered this before. So we can go to the next one. If FFA is not available, can OCTA replace it? Yeah. I think… The point I was trying to make with all those case examples in showing you the OCTA images is that OCTA can be a possible replacement, in a sense, for FA. Now, FA is much more readily available. So it’ll be much easier to use and find in the community. But there’s been… Yeah. There’s been a lot of studies and a lot of new data looking at OCTA findings. And the utility of OCTA. And I think that nowadays, OCTA, while not necessary, it really provides a lot of information that you can see in addition to FA. FA is not done as often as in the past for diabetics… Is OCTA a safer option, especially as there are no risks… I answered this. In your opinion, is there still any role for fluorescein if one has OCTA? Similar question as before. Is there any specific condition which fluorescein may pick, which an OCTA cannot? I think just one of the maybe limitations right now of OCTA is that you can’t… It’s really hard to get peripheral… To see peripheral pathology. So some of the OCTA images I showed were swept source OCTA, and just with your standard OCTA machine, you’re not really gonna be able to get that far out. So in peripheral vascular disease, I think your sickle cell retinopathy, cases of diabetic retinopathy with very peripheral areas of ischemia… OCTA may not… May still not be the most practical or the best option at this point. What is the meaning of grid laser and focal photocoagulation? So this is just going back to the ETDRS, they looked at… With focal photocoagulation, they essentially treated focal microaneurysms that were associated with leakage and macular edema. And then the grid laser was basically like a pattern grid laser that treated the edema directly. How do you differentiate diabetic papillopathy from other forms of optic neuropathy? I think that diabetic papillopathy is a diagnosis of exclusion. So a lot of times, patients may not be symptomatic from diabetic papillopathy. But if you see nerve… Optic nerve edema in a patient with diabetes, that’s something… This diagnosis is something you should think about, obviously. But I would say that it’s still important to rule out other causes of papillopathy first, before you make the diagnosis of diabetic papillopathy. Do you know what the potential new classification for diabetic retinopathy involves? I’m not sure what this question means. I’m not aware of any new classification. So I guess if I don’t have any clarification, I’m just gonna move on to the next question. What does diabetic retinopathy worsen… Why does it worsen in postcataract surgery, and why sudden tight sugar control significantly worsens diabetic retinopathy? I think for post-cataract surgery, probably because… What is it? The diabetic retinopathy is… A lot of it is because of loss of pericytes and the tight junctions. In the cells. So everything is very leaky. So it’s like after cataract surgery, you’re just more prone… The blood-ocular barrier is disturbed. And you just have a more… It’s sort of like a proinflammatory environment that will… That promotes leakiness of the blood vessels. So that’s probably one of the reasons why diabetic retinopathy worsens. But why does tight sugar control significantly worsen diabetic retinopathy? That I’m not sure of. I do see and I do acknowledge that it occurs. But I would have to look into that and see why that’s specifically the case. According to the panorama study, can a diabetic retinopathy case downregulate from severe to moderate NPDR or from moderate to mild NPDR? I know the panorama study looked at moderate to severe NPDR. And they also used the diabetic retinopathy severity score. So… Yes. I would say that there obviously must have been cases where the diabetic retinopathy score improved. From the severe, moderate to severe, to mild to moderate. Yeah. How best… Oh, there’s a lot of questions here. I realized… We’ll just get to as many as we can in the couple minutes that we have left. I didn’t realize there were so many questions here. So how best can diabetic retinopathy be treated? Aren’t clear for me… Yeah, I think the diabetes can be treated. It’s not a one size fits all approach. You know, we have options available. PRP, anti-VEGF, these days. I mean, depending on the issue. Right? There’s DME. You have anti-VEGF, you have… Laser, you have steroids. Not a one size fits all approach. Can we differentiate between hard exudates and drusen? Yeah, you can. If you get an OCT through it. Then hard exudates are usually intraretinal and drusen are… Under the (inaudible). In patients with return of edema following initial anti-VEGF treatment and good vision, how long will you review without treatment given the history of not having a good… Yeah, if you give anti-VEGF and you don’t notice any difference with the treatment, I will offer observation for them. But then I still would follow them in about one to two months or so, to ensure that things are not getting worse. Is there any contraindication of anti-VEGF in pregnancy? And at what age? I generally will try not to use anti-VEGF in any trimester of pregnancy. I think it’s probably worse in the first two trimesters. But… Yeah. No. I would not use anti-VEGF in pregnancy. Where do we put diabetic papillopathy in the classification? There really is not… It’s not really part of the classification. It’s just another sequela of diabetes that can affect the optic nerve. It’s not really part of the classification itself. What is the superiority of new anti-VEGF over the old one regarding outcome and dosing interval? You would have to check the studies. But the dosing interval — it’s less. It’s supposed to last for three or four months. The… Regarding outcome? Outcome is supposed to be non-inferior. To the existing anti-VEGF agents. And again, faricimab targets two receptors. So it’s not just anti-VEGF. It’s also the angiopoietin II receptor. What’s the role of NSAIDs in non-central DME? I mean… NSAIDs… I’m assuming that this question is topical NSAIDs. It’s not traditionally used for DME. Because the inflammatory… The pathway is more like VEGF-mediated. And less so inflammatory-mediated. So that’s why usually people don’t really use NSAIDs for DME. If the patient doesn’t have any history of diabetes, even in the family, is there any chance to develop diabetic retinopathy? Well, they can’t develop retinopathy unless they have diabetes. So I mean… These patients obviously would have to have a diagnosis of diabetes first. And then, you know, it really depends on a lot of things. It’s systemic control of diabetes, or if they have metabolic syndrome, or something else that kind of makes their whole situation worse, then they can develop… May be more likely to develop retinopathy. Maybe I’ll answer two more and then we’ll wrap up. What’s your best option for early PDR? I usually will just go ahead and treat early PDR. Not necessarily… They don’t have to necessarily meet high risk criteria for me to treat them. If I do see signs of PDR, then I essentially… If they don’t have edema, then I usually will just go straight to PRP. How do diabetic retinopathy affect myopic patients? How do we prescribe glasses to myopic patients with diabetic retinopathy? I think the biggest thing is probably diabetic macular edema. It’s not specific to myopic patients. But I think that if a patient has diabetic macular edema and it’s significant, it can definitely change the prescription. So I think that we just have to be aware of edema as possibly changing the prescription and making sure that they’re treated appropriately and adequately, before they’re given a prescription. Thank you all for attending. And for your participation.