Lecture: Diabetic Retinopathy: Advanced Clinical Techniques and Diagnosis for Patient Monitoring & Management

DR. DOLZ-MARCO: Hello, everyone. And thank you so much to the Cybersight team for allowing me to present today in this webinar. And the topic will be Diabetic Retinopathy: Advanced Clinical Techniques and Diagnosis for Patient Monitoring & Management. I’m Rosa Dolz Marco and I’m a retina specialist working in Oftalvist Clinic in Valencia, Spain. And I hope to learn together in the following minutes. And the first thing we have to really remember is that diabetes is currently a problem worldwide. It is increasing its prevalence year-after-year. And now with the tenth edition of the IDF Diabetic Atlas, they have increased the number of prediction for diabetic number of patients in 2045. Right now we have about 537 million people worldwide with diabetes. And this is going to keep increasing, as I was mentioning. But the problem is that it’s increasing in a different way, depending on the area we see. If you see Europe, it’s going to increase about 13% in the next 20 to 25 years. But if we look to Africa, for example, it’s really impressive. Because it’s expected to be increasing about 134%. So, that’s a big issue for those countries. And the other problem is that right now about 10% of the population — of the population worldwide — is suffering diabetes. But almost half of these 10% is unaware of this condition. So, that’s a big issue, especially for the screening of this population and the diagnosis and treatment. And we are going to discuss these things later on.
By 2045, the number of adults with diabetes is going to be expected to be about 783 million. And that’s about one in eight adults worldwide. And those were the numbers for diabetes itself. The numbers for diabetic retinopathy, they are, of course, they are going to increase itself. About 35% of those diabetic people, they are going to develop any degree of diabetic retinopathy. And about 11% of this population is going to develop sight-threatening conditions. So, they are going to decrease the vision. And the problem is that maybe those are the ones that are going to really go to the optician or the ophthalmologist in order to check on the patient. But many of those without signs, they are not going show up early.
Those were the global numbers. But I work in Spain. And this is a quite recent work in my country, in Spain. And it’s true that the prevalence of diabetic percentage — it’s going to increase, that’s the blue bar in the graph. And as seen worldwide. It’s increasing. But if you see the increase in diabetic retinopathy, it’s increasing. Starting about ’28. Why is that? Why in Spain are we increasing the cases? The first is we have improved the diagnosis of diabetic mellitus. Now with screening, it’s diagnosing diabetic mellitus. And a lot of the patients we are diagnosing now, they don’t have any complication of the diabetes right now at the diagnosis. So, that’s why the numbers vary a little bit. Also, because with the screening protocols that we have right now working, the detection of diabetic retinopathy, it’s also becoming earlier and earlier because this screening protocols with technicians performing the photographs and then sending to general practitioners. It’s working quite well. And also, and not least important, we have better treatments for the systemic and glycemic control of these patients
So, my first point that I want to highlight is that, okay. We have a lot of diagnostic tools. We have a lot of cool cameras and a lot of technology. But we found a good work and most especially collaboration, we cannot really diagnosis early diabetes. Sew, we need endocrinology, primary care working together with us. And also, we need to focus in patient education. Because if we want to really those patients to become part of the screening, they need to be informed and they need to understand the importance of an early diagnosis.
What about screening? If you’re really interested in a screening its, I really recommend this paper by Dr. Ramasamy, it was in India. I think it’s good because it describes a lot of the concepts of the screening. The first thing is you can, for example, do a screening in an opportunistic way while they are going to the endocrinology or the primary care checkup. They can also do the screening for the retina. But you can also schedule a systemic screening for all the patients that are being diagnosed with diabetes. The other point is that we have many, many options. We have traditional cameras. Normally 45 to 50 degrees, but also wide field and ultra wide field imaging. But also we have smartphone-based cameras, or hand held cameras. That’s really important because sometimes we are not really doing the screening in the same place every day. So, that’s a good option for those mobile screening sets.
Of course, screening has a lot of challenges. As we mentioned, we don’t have early symptoms in diabetic retinopathy. So, patients may show up only when they feel something. When they have vision complaints. They cannot do regular things, they cannot drive. So, that’s quite late because, of course, we will have a lot of signs in the retina.
And, of course, the problem with costs are really important because those cameras I was mentioning are not cheap in general. There are cheaper version. But in general, it’s going cost. And all the people working for this screening, it’s also costly. But now with AI and deep learning protocols, I think we can really adopt these screening tools for more people. So, we can go for wider populations. So, I think these AI tools are really going to help us lot in the screening. But when looking at retinography, what are we looking for? Well, the first thing we are looking for, of course, are microaneurysms. These are the first signs, and look for hemorrhages, exudates, intraretinal microvascular abnormalities. Those are the classic findings of diabetic retinopathy. And normally we use color fundus imaging or dilation imaging in order to evaluate that. It’s not the same as having these series of hard exudates pointing toward the fovea. We should treat this patient with macular edema. We have images. There’s laser there, the spots, and more spots in the patient in the center, and microaneurysms. And some tiny exudates there. But if we look careful, we should look for all these abnormalities and check up if those proliferation or intraretinal microvascular abnormalities. If we look closely to the fovea, sometimes we can see in the retinographies we can see the spaces. Edema. Those are the things, proliferation, edema, that we are looking for. Again, this patient, it’s not the same. We have this band of fibrotic tissue above the retina with these hemorrhagic signs. More massive here in the image in the right where we can see this appearance of the hemorrhage, meaning it’s between the posterior hyaloid and the retina. This is probably going to be diabetic retinopathy. We need to urgently treat these patients.
So, not only we look for microaneurysms and all these classic signs, but look for macular edema, neovascularization, vitreomacular traction and retinal ischemia. They are going to change the way we treat our patients. And how we see these signs. Well, we are lucky as retina specialists because we have a lot of tools. We have color fundus, but we have also dye-based angiography and flore-based angiography for these conditions. We have OCT and OCTA. It has changed completely the way we see our patients. And I’m going to also focus a lot on OCT and O CT angiography because I think it’s really important for the management of our patients.
So, let’s start with a classic. Color fundus and fluorescing angiography. Not talking about ultrawide field. But we will also touch this topic. But in general, color fundus angiography. With color fundus angiography, we have the classification of diabetic retinopathy. This was based on a modified classification of the Airlie House classification. It’s most used in clinical trials is the ETDRS trial classification. The problem with this classification of 12 steps and a lot of levels is that it’s really complicated for a daily practice. We don’t have the time to carefully — well, we should carefully review our patients — by don’t have the time to carefully classify with all these details. So, now there is the classification that is widely used is the International Classification. And this is where we separate no, this is visible. Then mild, non-proliferative disease. Moderate, non-proliferative disease. Severe, non-proliferative disease, and proliferative disease. And that’s normally what we do in the clinic. It’s non-proliferative with mild, moderate, or severe degree. Or it’s proliferative. And based on that, we change and assess the management of these patients.
And the good thing is that both classifications, but especially the international which is the clinical one, the one that we use in daily clinic, real life. Not in clinical trials. Where ETDRS is more used. Those classifications are reproducible. They’re really well-validated. We have a lot of data, a lot of historical data on this. And they are robust in order to predict important outcomes of our patients. Problem is that we have a lot of limitations. They only rely on the seven fields of the ETDRS. So, that means only about 30% of the area the relate that. They don’t really predict for the incidence of diabetic macular edema. They mainly predict for the proliferation. But we don’t really account for diabetic macular edema prognosis. So, and that’s the most common cause of visual decline in our patients with diabetes. And that’s important. They also don’t include functional data. So, no visual acuity or other functional data. They don’t really include as classification or early changes these narrow or new regeneration changes that could happen even earlier than the vascular changes. And also, when we treat patients right now, we have seen that we can regress the degree of diabetic retinopathy if we treat with laser — with PRP — proliferative condition. And the neovessels regress. Or we had neovessel, but we treated and they regressed. That’s not really included in this classification. We can’t really note that in order to be aware of these things. So, those are important limitations to be aware of.
And the other important things regarding classification is the field of view. It’s not the same using a 45-degree photograph where we can see, in this case, that we have really here an area that we should highlight. It’s better to have a wider area. But still, it’s those ETDRS and International, they will be based on this kind of area. So, about 30% of the retina. And not the wide periphery.
So, what about the wide periphery? So, for example, these patients with diabetic mellitus type 1 for 40 years, not especially good control. And we can see just mild hemorrhages. Some microaneurysms, micro exudates. If we increase the field of view, we see one hemo in each eye and probably a tiny one here. So, probably we will all set up and degree this one as mild nonproliferative diabetic retinopathy. But if we increase even more the field of view, we can see that we have a lot of emerges, especially in the far periphery. And these will end up being moderate, nonproliferative diabetic retinopathy. This is the fluorescing angiography. Where we can see more microaneurysms, of course. We can see also microaneurysms in the periphery. And start to see some areas of capillary closure, especially in the far periphery. So, increasing the field of view is also important. And also having fluorescing angiography is going to help us in increasing the number of signs we see. This is the fovea for the same patient. We are not really expecting to have a lot of things. His vision was 20/20. So, really good in the center. But mainly diabetic retinopathy in the periphery. Is that important? Well, the thing — the answer is of course it’s important. With ultra-wide field imaging protocols, we can have an image about 12 degree — 200 degrees of the retina. So, that’s about 80% of the retina. Either with one short in some devices, limited devices, but mainly with montage of these images so we can be really wide in the retina. They could be used for screening. Because especially many of these prototypes and devices, they work with no — and as I was mentioning, you can do single image with 1200, 200, but not every device could do that. But montage can allow us to see bigger pictures.
And the thing is if you analyze and classify diabetic retinopathy comparing ultra wide field imaging compared to the seven ETDRS fields, you will see that 15% of patients have greater stage of the diabetic retinopathy when grading also the periphery as we sue in the case I was showing. And what happens with those patients that have predominantly prolifeations? Those are patients that are at higher risk because those lesions are 50%. Half of the lesions are outside of the ETDRS. And they have increased progression risk for developing and progressing to steps of diabetic retinopathy in four years. And also, 4.7 increased risk for progression to proliferative diabetic retinopathy in four years. So, that’s a big number and it’s important to really be aware of that. Okay? So, those patients with really mild — with far periphery involved, be aware that they could really progress worse than those with signs in the center.
Let’s see another example. This example shows already exudates here. Some hema. Some aneurysm here. And some changes here too. And if we see the wide field image, we can see more hemorrhages. Here, another area with some funny-shaped vessels. Always look for these funny shape. It could be neovascularization and proliferation or it could be intraretinal microvascular abnormalities. So, we should really be careful on seeing that. Fluorescing angiography, of course, is going to add a lot of information. We can see really clear that those funny-shaped vessels were neovessels leaking. So, it’s really important. Also, fluorescing angiography allowed us to see a lot of patch you areas of ischemia in the periphery, so it’s really important. This is the fellow eye where we can see all these areas of neovessels with leaking in the middle and late phases. And again, a lot of areas with ischemia. So, wide field and ultra wide field fluorescing angiography, it’s helping a lot because they provide with additional and complementary information to the color fundus. And this was analyzed by the Protocol AA. But the DRCRnet. And they concluded that ultra-wide field fluorescing angiography complement the color fundus photography. And if you have greater areas of retinal non-profusion and these regions are predominantly peripheral, those patients are, as I said, with higher risk of this worsening. This is also in four years. So, this additional information has prognostic information for our patients. So, it’s really important.
And what about other modalities? So, this is OCT complementing. We don’t have edema. That’s good. But what else do you see? I’m going to stop a little bit so I can drink and breathe. But you think on the things you see in the OCT. And we see other things. We see this area of thinning, retinal thinning. And this should always pop up in our mind when we are looking at diabetic people. But we also see this area of thickening of the posterior hyaloid. This is not thickening. This is proliferation. So, this is new vessels, okay? Neovascularization in the retina, it’s always going to show up above the retina. And normally, with the posterior hyaloid being — or all these new vessels rubbing in the surface of the retina.
So, OCT, we are mainly using OCT for evaluating edema. There is fluid, no fluid, thickening. Okay. But we have a lot of other things that we can see at the OCT. Of course, the thickening could be linked to the areas of leaking and edema in fluorescing angiography. This was really studied at beginning of the OCT when we were starting to use OCT in daily practice. And we can guide even photo-correlation or treatment with this OCT, of course. But it’s also important to have an idea or — on how we are classifying this maculopathy. Diabetic edema. It was happening with retinopathy. We were using only color fundus photography at the beginning. With this clinically significant macular edema in the center of 500 microns centrally in the macula. Clinically non-significant when it was outside. But also with fluorescing angiography and the focal, multifocal and diffuse areas. But with OCT, we can be really precise. Quantifying the amount of thickening and also locating really precisely this edema. Macular edema was classified — really this was one of the widely-used classifications by Panozzo in 2004. But I think it was quite complicated and that’s why normally it’s not implemented in the clinic. We don’t really assess the morphology or the traction. We assess in a different way instead of pointing and numbering of this assessment.
They have really updated this classification by Panozzo and the group. But again, you have to address the thickening and gray dot. The cysts in gray dot. The membrane, in intact or absent, the retina, traction, and in the end, you have to point to too many things in order to stage diabetic macular edema in early, advanced, severe, or trophic. So, I think the problem with this detail and super-strict classification is you have to point to too many things. And in a busy clinic, maybe, you don’t have the time to do that.
That’s why we proposed a long time ago this classification, thinking more on how we think as clinicians. So, normally in order to treat edema we think if there’s central involvement or not, if it’s peripheral or it’s central or it’s marginal. Because you can maybe treat it with laser. If it’s the extension, it’s really wide or less wide. And especially the presence of traction. Because if there’s traction, we can maybe choose these patients for better retinal surgery.
But my point here that was I think it’s — there’s less systemization in the diabetic macular edema compared to the diabetic retinopathies. And this the example of the proposed International Information. But it’s just quite simple. Presence or absence of edema. And grading mild, moderate, or severe. But this is based on color fundus photography. So, you miss a lot of the details that Panozzo was proposing. And what are those details that we can see with OCT and OCT angiography? We can analyze, of course, the location. Fluid could be intraretinal fluid. We think the layers of the retina. Or it could be subretinal. It could also have hyperreflective material within the cysts. So, not all the fluid is going to be high pole reflective. And also, we can have confluent cystic spaces. It’s not the same as having just some tiny cysts around the fovea that are having larger cysts here. You can see that in these area or this one, the content of the cyst is more hyperreflective compared to other areas where it’s hypo. Is this important? Well, yeah. That means that the contents is different. And we are going to see that it could appear different in OCT angiography. We will see. And what about the confluence? It’s not the same as having this huge cystic space compared to having just some little cystic spaces with a more preserved anatomy of the retina.
And if we look at additional information that the OCT angiography provides, this confluence central assists with a lot of dimension, diameter. Normally associated with non-preservation of the fovea zone .
so, there loss of the vascularity and signs of the ischemia in the OCT angiography allows us to diagnosis them in the spaces. This is the intermediate plexus and the deep capillary plexus. Also showing this loss of capillary provision.
The other sign that we should really look for is distortion of the internal retinal layers. And if you see above, we have a lot of signs of ischemia. So, thinning of the retina. But we can still draw the retinal layers in this patient. But if you look at the patient below, we see thinning. But we cannot really separate and define the layers. So, this is DRIL, okay? Disorganization of the internal retinal layers. It’s highlighting all the hyperreflective content and not being able to differentiate between the different layers of the retina, okay? It becomes all like a mass with no edges and sub-layers. And that the distortion of the outer retinal layers, it could be called DROL. Or also normally it’s reflected as the presence — or preservation or disruption of the ELM and the ellipsoid zone. So, external membrane and ellipsoid zone of the photo receptors are the most important factors for the visual neuropathy in our patients because of the disruption of the outer retinal layers. Could also be referred as DROL. As you can see here in both examples.
And this is another example where we can see that it’s really difficult to differentiate between layers in these patients. So, we have DRIL. But also we have some distortion of the retina especially in the image below where we can have all this hyperreflective material. And all the disruption of the external limiting membrane and the ellipsoid zone.
What about the content? I was mentioning before that we can have this hyporeflective content or this hyperreflective content. And this is due to the presence of lipoproteins and different aspects. So, in OCTA, we have the cystoid space with no flow sign. But sometimes we have this mild flow sign in these areas of the cyst. And that’s because some of this content in the cyst, it’s moving because of these lipoproteins. They are moving around in the cyst, within the cyst. And this has been described as SSPiM. Let’s see another example. This is sealed off flow. It’s not flow of the blood cells in the vessel. But it’s something moving within the retina, but it’s not blood. It’s just the content of the cyst. If we look at the RBS cam, not the visualization, we can clearly see that some cysts are hyporeflective and we don’t have any movement there. But those with hyperreflective content, they can show this flow signal. Not related to movement of blood cells. Again, movement just of the lipoproteins within the cystic space. And this is the same patient with the superficial vascular plexus, the intermediate capillary plexus and the deep capillary plexus where we can clearly see all the cystic spaces with the sealed off flow. And this again is called SSPiM, suspended scattering particles in motion. Because those are particles that are moving within the cyst, but not blood.
And this is another example where you can see that the fovea is preserved. You can have nice capillary profusion. Also, here, fovea is preserved. But you have this — all this area of sealed off flow. That doesn’t really correspond to any vascular structure. It’s just — oh, sorry. With some hyperreflective content.
And what about this patient? This is the superficial but vascular complex, sorry. Superficial vascular complex. This deep capillary complex. And this is the vitreous area. And this is important to know because patients with diabetes may have neovascularization. And this is in the lab OCTA that we are going to see when we are analyzing the presence of new vessels. But sometimes we have the posterior hyaloid just detaching or almost detach from the retina, but attach to the optic nerve head. And with the movement of the eye, we can have some mild movement. So, we can have these areas of sealed off flow. So, you will be same as sealed off flow. So, movement like we described in this beam. But related to the posterior hyaloid. Which is a tissue that it’s moving itself in a different way than the retina is. So, always important to only — not only analyze the reconstruction of the OCT angiography, but also the scan with flow overlay. Because we are going to really understand a lot of this condition. We don’t see really thickening here. So, there’s no way there’s vessels there, okay? If we are not really sure, we could also perform fluorescing angiography to see if there’s leakage or not in the mild area there.
What about microaneurysms? Is there an importance to look at those microaneurysms in the OCT? Well, we can really analyze a lot of things in microaneurysms, especially the contour. Because normally when contour is really hyperreflective and continues, those are normally microaneurysms that are not leaking. But when we start to see these, we lost this continuity and we start to see patchy areas of hyporeflective contour. Those are normally, as I said, with cystic spaces. Those are microaneurysms that are going to leak. And this was also published a long time ago by Dr. Horii and colleagues and they described this sign we should look for in microaneurysms. When we lose this ring sign, then we have this leaky microaneurysms. We can also analyze these leaky aneurysms in an enface way. With CT. If we see a really hyperreflective structure, really homogenous, it’s non-leaky microaneurysms, but if we start losing this hyperreflective contour and structure, those are the ones that are leaking.
And we can also nowadays combine not only a structural OCT, but also OCT angiography. So, we can see which of these microaneurysms are profused and which are non-profused or partially non-profused. We have a lot of information of these microaneurysms. What about hard exudates? We could be seeing the earliest stage of exudates as hyperreflective foci. But also, we should be really worrying when all these hard exudates are pointing towards the fovea. Because we know if they deposit in the fovea, they can do this kind of proliferation that I was showing before with the distortion of the outer retinal layers. And this is really important because it’s going to decrease the visual acuity in our patients dramatically.
An ischemia. Can we really assess ischemia with OCT? Normally we talked about fluorescing angiography, and, of course, if you want to analyze the periphery, it’s sometimes faster and better to do fluorescing angiography. But ischemia could be really analyzed with OCT. And now with OCT angiography too. Let’s see at OCT. We can analyze caudal spots and paramacular, middle Mac lop think, pericentral middle maculopathy. And they are affecting the intermediate layers of the retina. This is the early sign or acute sign of ischemia. Hyperreflective of the layers. When this acute phase is fading and we have the chronic phase, we will have thing of the retina. That’s what we were seeing before in other cases I was showing. So, acute, you will have hyperreflective. But then when you have this distortion and this irregularity of the outer nuclear layer, this means that all these areas are affected by ischemia in the deep complex.
And this is in combination with multicolor. Because it’s also useful in the differentiation of the level of ischemia. With OCT, we can see that the hyperreflectivity, it’s not nerve fiber layer. This is superficial ischemia, the spots. We will see the whitish-patch you area. But really it’s showing a white here. With the multicolor in the paracentral acute middle maculopathy, we can see the grayish appearance. It’s not that wide, it’s not covering vessels. It’s more in the middle of the retina layers. And the OCT also highlights that with only hyperreflectivity in the middle layers and this highlight of the external plexiform layer. And this is the chronic stage. We were talking about hyperreflective of the layers. Now we are only seeing thing. When we see patchy areas of thinning of both the internal and medial layers, we know we have superficial, per mediate and deep capillary affected. When we only see the affected the outer layer with this color irregularities, it’s more on the deep. But sometimes we have this mix of superficial and deep retinal circulation movement. And all these cases are showing the same patchy areas of thinning. So, whenever we are evaluating if a patient with diabetes has edema, we can also evaluate if we see any of these irregularities. Because those are really signs of ischemia, and those are really common.
But also, we can use the thickness map. And thickness maps are really useful. It’s just a view, and we have this bluish areas. So, retina should be more grayish and somehow — or yellow around the central area of the macula. But if we see these areas of blue in the thickness map, we can correlate directly with OCT angiography and we will see these areas of capillary drop out. So, we have ischemia, okay? So, this is another way to visualize these areas of thinning with the scan in a faster image. Just looking at the thickness map. And look carefully at this thickness map. So, sometimes we are just looking for thickening, okay? So, this orange/reddish, even white color. But we can also check these areas of thinning. So, bluish area. But look at this tiny area of thickening next to the ischemia. So, this is quite suspicious, okay? Because we have ischemia, but we have something growing there. So, something that the thickness map is going to show because we have neovascularization. So, OCT careful analysis could be really useful in order to maybe avoid fluorescing angiography. Because we know this patient has proliferation, okay? And it’s going to change completely our management. This is another example where we can see these areas of ischemia in the OCT angiography that are going to be areas of thinning. And again, this is a patient with fluorescing angiography and patchy area of ischemia here. And we can see that the ischemia corresponds to an area of thinning. So, bluish color there. So, again, ischemia, really important to be analyzed. Also, not only in fluorescing angiography, but also OCT and OCT angiography. And what about proliferation, okay? It has two functions. We can plan the surgery if our patient requires surgery because it’s of high risk of detachment or attraction. But also, we can differentiate new vessels from intraretinal vascular abnormalities. So, new vessels are going to grow above the retina. And inter-retinal microvascular abnormalities are going to stay within the retina. So, those are both funny shaped vessels in the fundus. But with an OCT over these vessels, we can differentiate. So, proliferation and new vessels are going to be always above.
And we can carefully check with infrared image, fluorescing angiography, these leaky vessels. So, new vessels. But we can check with the OCT that always looks as proliferation in the vitreous area. So, above the retinal surface. And always looking the same. Okay? Sometimes they have like an area of proliferation. Sometimes it’s more focal. And we can — with the OCT analyze the degree of traction on the surface of the retina. So, for example, the patients below in the bottom part, these two patients might benefit of some kind of surgery. If we think that the patient is at risk of retinal detachment.
But it’s still — we can analyze with the OCT angiography this proliferation. And start treating when we see that the traction, it’s not a problem. And we start treating so we can resolve the macular edema without treating with surgery this patient. And that’s going to be better if we want to continue treatment with anti-VEGF. And what about ultra-wide field angiography. This is a trending topic. Sometimes it’s cool images, but in the clinic, has also some limitations. It’s good to have this image. But it’s going to take quite a lot of time because a patient should be helping because it’s a montage of different images. Or this, or the one with proliferative diabetic retinopathy. But if we want to analyze even further the retina, we come to have problems in the segmentation because of the shape of the eyeball. And this is an issue when we want to really analyze if there’s ischemia in the periphery. Because we don’t really want to have issues with segmentation. We want to be sure if there’s ischemia or not. So, sometimes it would be easier to perform a classic fluorescing angiography. Again, this is an area of ischemia. But I don’t know the extent of these ischemia in the periphery because it’s really marked with other artifacts of the OCT angiography. I’m coming to the end of this talk. And I want to summarize with this paper. And I think this is the consensus that internationally they have achieved. And thing that a standard color photography, and color fluorescing angiography, and even wide field, we can stage diabetic retinopathy, but we need more evidence with other modalities. So, nowadays in order to analyze the retina, we have a lot of information with color photography, especially standard. We also have standard — and a ultra-wide field fluorescing angiography. We need more on fundus, and especially OCT angiography. And that’s why because, well, CFP with the standard field of view is cheaper. It’s really nearly universally adopted for screening. And diagnosis of diabetes. So, this is the way that we should be working still. So, it’s not really old fashioned. It’s just still up to date and we can just see it. It’s through that if duo a montage of the seven field ETDRS, we can also assess the periphery and know if this additional information is important. Okay? Because we know additional information from the periphery, as I mentioned before, has prognostic value. But especially adding prognostic information with ultra-wide field fluorescing angiography could be really important because it’s really assessing the progression into advanced forms in really an important way, and complementary to the color for the images. And in fluorescing angiography, even though it’s a non-invasive modality, it’s true it has a lot of limitations. It’s promising, but still we have to learn a lot from this technique.
I just want to show the last case because I think this is the way I — at least I work in the clinic. I use ultra-wide field or wide field color images to do the staging. And I use ultra-wide field fluorescing angiography because it’s helping a lot in the planning of the laser and also in the prognostic information. So, I always use this ultra-wide field. And one of the things that I really — well, sometimes you can highlight these new vessels with green reflectance. And what I really use a lot is OCT follow-up over these areas of new vessels because it’s helping me a lot to see the progression when we perform treatment even with laser or ETDS. And we can do that with the structural OCT, but also with the OCTA and showing the nice progression of the new vessels. It’s really helping me a lot and I use a lot of detail information of these diabetes.
So, my last slide will be a quick checklist for these diabetic patients. What are the things that we look for? Changes in the OCT angiography with all this deep ischemia especially. We also check and differentiate proliferative and nonproliferative. This is with color fundus and fluorescing angiography, ultra-wide field. And, of course, we should check with the traction, if there’s traction with the OCT. For diabetic macular edema, if there’s central involvement or not, only with the OCT. And detailed evaluation of the internal and external retinal layers. And again, if there’s presence of traction.
And with that, I want to thank you for your attention. And now I think we can move on to the questions.
Okay. So, first we have a question of how we can avoid the neovascular risk and complications? So, we can’t really avoid it. But that’s why I highlighted that the earlier we diagnose diabetes and the earlier we start with this patient within a project or a protocol of screening, the better. Because we are going to really detect changes earlier. And we can prepare. Or we can change treatment. Better glycemic control. And we can schedule the patient in a different way. So, for those with mild nonproliferative diabetic retinopathy, those could be seen yearly. But those with signs of moderate to severe, we can schedule in a different way.
What is the fate of diabetic retinopathy proliferation, I think? You mean the rate? I think. So, the rate — so, sight-threatening diabetic complications are about 11% of diabetic patients. But those not only include proliferation, but also diabetic macular edema, okay? So, diabetic macular edema in fact is the most frequent cause of vision loss in our patients. How long does it normally take for systemic diabetes to cause diabetic retinopathy? So, it depends on the type of diabetes. So, right now protocol says that when you diagnose type 1 diabetes, since the diagnosis normally it’s when the disease has started, you can wait for up to five years in order to do the screening. But when you diagnosis a type 2 diabetic patient, you should start screening property cools as soon as you diagnosis that because you are note really — you couldn’t be sure of when the disease has started. Okay? Normally, yep. It could be like about five years. But it’s — that’s an estimate based on the schedule of the screening protocols. What is the side effect of edema in each patient? Well, the side effect is that the visual acuity is really impaired when there is central involvement. And we should treat it as soon as possible. If central — if there’s central involvement, there will be the first option. Unless they are non-responsive, where we have also corticosteroids. Apart from the retina, is there any ocular sign that it’s diabetes? Can hyperglycemia cause some desensitization — and can it be used as one of the ways to detect diabetes? I will not say patients with diabetes have more symptoms of the dry eye. In fact, I will say they have less. Because normally they have problems with sensory nerves. But they can also develop cataracts earlier. So, this is another complication in the eye. And they can also have dry eye. But I would not say sandy or like itchy feeling. Or foreign body feeling. It’s a way of diagnosing diabetes. They should do blood test and that’s probably the best way.
What are the complications? I don’t know. What are you referring to. So, if you can reframe the question. So, what are the usual complications after the surgery? Well, I don’t know what surgery are you referring to. But if you mean the vitreoretinal surgery, usually there’s no complication. But when I was referring to avoiding doing vitreoretinal patients, if the patient is with vitrectomy, the drug may last less. But there’s no other complication. How can we differentiate an exudate from a drusen on imaging the retina? Normally hard exudates are around a vessel or a microaneurysm and they form this circular appearance. Or they point towards some direction. Especially the fovea. And drusen, normally the classic soft drusen are located in the macula. And the color is more whitish with a rounder — round contour. The acetazolamide for DME, if you don’t have anything else, you can try. But I will even try, I don’t know. A steroid. Even periocular instead of acetazolamide because there’s probably not much effect. Injectable insulin in the progression of DR. The better the control is, the systemic control, the better. Because we can — yep. Control better the progression. But you should treat no matter what happens with the metabolic and glycemic control of the patient. If the control is better, the prognosis of the patient long-term is going to be better, of course. Why kidney disease is considered as risk for the progression of diabetic retinopathy? So, the thing is that if you have also kidney disease, it’s meaning that you have a lot of impairment over the microvascular structures in your body in general. So, those are patients that are at higher risk for progression. Can you suggest latest treatment? Well, latest treatment I would — my first option is always anti-VEGF. And we have many options right now approved for diabetic macular edema. And if there’s no response — I’m talking about diabetic macular edema — if there’s no response, you can also complement with steroids. And also you can use some laser treatment when you have this peripheral areas of thickening. And for diabetic retinopathy, I normally — I still keep using a laser. It is — is it possible to have diabetic retinopathy even after 25 years of diabetes? Of course. There are patients that never develop diabetic retinopathy because the control is good. In fact, it’s estimated that the prevalence of diabetic retinopathy is about 35% of the overall diabetic population. How do you incorporate based on knew row degenerative changes as part of the pre-clinical diabetic retinopathy monitoring? So, visual function. Normally we use visual acuity and nothing else. Because in a daily clinic and you don’t have time to include contra-sensitivity, reading speed, and other tests. Or even visual field. But it would be interesting. And there are a lot of papers on this topic. For the neurodegenerative, you can access the thickness of the ganglion cell layers, for example. Because there’s involvement of this layer in diabetic patients. For how long are anti-VEGF injected in diabetic macular edema? Forever and ever. But at the requirement of anti-VEGF is decreasing over time. Normally it’s about mean number of seven injections in the first year. About four injections in the second year. Two injections, three in the third year. So, it’s really behaving better and better. And this is when you are using treat and extend protocol which is my preferred protocol for treatment with anti-VEGF right now. Do you observe macular edema or treat if vision is good? So, if vision is good, I really trust — that’s the main difference with AMD. With — it’s related to macular degeneration. Here with diabetes, we want achieve the good vision. Even when sometimes we have a little bit of fluid, visual acuity could be 20/20. So, I will not start patient — treatment — sorry, with visual acuity 20/20. I will observe. Do you recommend routine ultra-wide field fundus photography for OPTOS for diabetic retinopathy? If you can have OPTOS or other wide-field image, I think it’s useful in general for screening the peripheral tear. It’s useful not only for diabetic retinopathy, but assess with them. May I know what is DVL? I don’t know what are you referring to? How to know artifact from ischemia in OCTA. Well, that’s tricky. But I will suggest always look for the segmentation on the scan, not only the fast visualization. I will check the transverse, also the B scans. So, OCT with flow overlay. There are any studies in genetic defect or genetic variations with diabetic retinopathy? I mainly talk about diabetic retinopathy type 2 and also type 1. But there are some variations and rare variants of diabetes that are genetically variants. So, yeah. How to minimize the artifacts maybe for OCTA? Well, I think all the companies are working on that. But it’s a tricky technique. So, it’s a quite complicated to really segment all the retina with the shape of the retina. So, but technology is becoming better and better. What are your expectations to our optometrist role when they are seeing diabetic patients? So, I think I didn’t — well, I included optometrist because depending on the country they really work as primary care for those patients. But I think I don’t have any particular expectation because it doesn’t really depend on me. I think they work a lot and they — if we worked together with them, it’s better as ophthalmologists. Because they have a lot of population in their hands and they can do a lot of good work for screening of these important conditions. Is there any alternative to PRP? Yep. You can use anti-VEGF. But then the patient should be going normally monthly to your clinic. So, it’s really costly. So, but it depends. Maybe some patients will benefit of this anti-VEGF treatment. Thank you for your lecture. I’d love to know what camera do you use in taking images? Well, I work with a Spectralis from Heidelberg and normally do spectroscopy with that. And for a wide field color image, I use another one. Diabetic macular edema and anti-VEGF which anti-VEGF is good and intravitreal steroids not working? The most recent is from Roche, it’s approved in Europe for diabetic macular edema. That will be the latest. And other options that are on the pipeline, for example, the PDS. That you inject in pars planar. And with the field map it’s going to release slowly the drug over time. The poor delivery system. Yep. Which molecule prescribed to treat? Well, the good thing is that right now we have — well, we don’t use — I don’t use in the clinic. But we have the visio map. We have a others. You have a lot of options. Also, you have all the steroids. It’s good to have many options so you can choose depending on your patients. What is a treatment modality for sub-hyaloid hemorrhage? Well, it depends on the degree. And if you have treated already with PRP or not. And you have traction or not. So, it’s not only sub-hyaloid hemorrhage per se. But you have to really assess the presence of traction, risk for retinal detachment before deciding if you want to do PRP. So, just laser. Or you want to really assess with surgery. Is using angiotensin-converting enzyme really effective in slowing the progression of diabetic retinopathy? I don’t really know. So, but probably if there’s data on the endocrinology side, it could be. After anti-VEGF injection, which is the best in follow-up? Color fundus, OCT, or OCTA? Well, if you want to check up for edema, I will go for OCT. OCTA could be useful in order to assess ischemia. And color fundus, it’s always good to have. So, I will do everything. But OCT of course. How do you differentiate a neovascularization of a disk versus neurovascularization and IRMA? So, clinically, with OCT I will say, OCT is really useful. But, of course, you have angiography. And normally at baseline of for sure you should perform angiography. If you’re suspecting proliferation. Because you can really assess all the areas of neovascularization with OCT. It will take a lot of time. But when you have some patchy areas of neovascularization, my point was that you can follow-up with OCTs to see the regression and it’s another way to have information of this over time. But for baseline, I will say it’s better fluorescing angiography. And for follow-up, you can follow-up with OCT. In the UK, we are limited to PRP for PDR and can only use anti-VEGF therapy if PDR persists despite complete PRP. Yeah. We are not that limited. So, you could be able to choose in Spain. But it’s mostly — I think it’s most costly efficient. So, because you do PRP and normally it’s going to regress in every case. So, yeah. It’s kind of the same. It’s not — a lot — I don’t know a lot of people treating with anti-VEGF that are PDR. Whether not to prescribe glasses for a diabetic person? Well, if the patient is going to under — undergo cataract surgery, maybe it’s not the best option. You should wait. And if it’s not — there’s a lot of edema and you’re going to start treating, then you should wait also. So, once you require treatment because there’s some complication. Maybe you should wait a little bit and then prescribe the glasses after the procedure. Does the sub-threshold microsecond pulse diode laser ha a role in DME? Well, I think it’s less and less used. But maybe you have some timing microaneurysm and you don’t have a diffuse, really involved. Maybe there’s still some role.
How many years it takes to develop a proliferative after onset? We talked about that. Maybe up to five. But it’s speculation based on screening. Why do we look for diabetic retinopathy in peripheral retina? There is no risk in vision. Yes, but we have seen with the AA protocol and before with many other publications long-term, like following for at least four years, diabetic patients, that all of this additional information and this predominantly peripheral lesions in diabetic patients, they really give us prognostic information because they increase the risk for progression into proliferative stage. And they also increase the risk for advancing two steps on the diabetic retinopathy stage. So, there’s no vision per se. But there is vision risk because the progression of a stage of the diabetic retinopathy.
Do you regularly apply laser to the new vessels itself or just around it? I just do PRP. Not treating the new vessels itself. In fact, what you’re treating is the ischemia. The ischemic lesions around, normally. For how long do we have to continue giving anti-VEGF? Or is there any criteria to discontinue giving it? Well, I don’t think you should stop it unless it’s really benign. But it’s true that you need less and less. So that’s a tricky question because in fact that’s why classifications are also limited because we don’t really have information after treatment. What happens when we have regression of this retinopathy and we have also improvement of DME. How long? How we should really assess our patients? And which frequency? So, I think there is a lot of work on this and we need more data for the following years. Is there a contraindication to cataract surgery in diabetic retinopathy? So, I don’t think there’s a contraindication. If there is a patient with macular edema, I will suggest to perform anti-VEGF injection after the surgery, but within the day of the surgery. Because we know with edema and the surgery that could be worse. But not contraindication per se. To which extent can diabetic cause myopic shift related to time it may take? So, the thing is that, yeah. It’s good to have refractive changes because of the — both the thickening and thinning of the lens. But also, if you have thickening of the — of the retina, you can have hyperoptic shift. So, yeah. There is many things you can have in the refraction of patients. So, you should be careful. That’s why delaying the glasses could be related to cataract or edema.
Is there any way to go around classifying the extent of diabetic retinopathy in the setting of poor fundus view? Well, there is stage for no — so, poor fundus view will be even like the more advanced stage based on the risk classification. If you cannot really assess the fundus because of vitreous hemorrhage, then it should be really advanced. If you have cataract, I will suggest to take out the cataract before and then grading the retina. And if you — the cataract is so, so big that you cannot really see the retina, you can also perform maybe ultrasound before to be sure that you don’t have retinal detachment and that will require combined vitrectomy and cataract. Type 2 diabetes mellitus is on the rise and many patients are completely unaware that they have this condition. And diagnosis of the pathology is way late into this condition and a full endocrine evaluation is needed and patient education also. Plus, well — there’s no question here. Okay. Yeah. Systemic control. It’s important and patient education, yeah. Do you think that the steroids could be the first line of therapy in patients with DME? Not for me. I prefer anti-VEGF. There is an option. But I think it’s more a safe for the eye and no risk for a cataract. No risk for IOP increase. And they are really effective. So, I will use it as a second line in those refractory DME. For my country, can you help with this treatment? It is not available in most Africa countries. Maybe you refer to anti-VEGF. And faricimab. I wish I could help. I don’t know. But maybe Orbis and the organization can maybe help with that. If your experience, is there a definitive end to anti-VEGF once it’s started? Not really. No. You should always keep treating and checking the patients.
Well, perfect. So, thank you so much. I hope you enjoyed it. Thank you again to the Cybersight team for this opportunity and to Orbis for allowing me to present today. Thank you.