During this live webinar, we will discuss the current diagnostic tools and treatment modalities of polypoidal choroidal vasculopathy (PCV) and the management of various complications associated with myopia. The webinar will highlight the prevalence of PCV, a sub-type of neovascular age-related macular degeneration, in the Asian populations. Attendees will also gain further insights into retinal detachment, myopic traction maculopathy, and myopic choroidal neovascularization. (Level: Intermediate)
Dr. Timothy Y Y Lai
Clinical Professor (Honorary), Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong
Honorary Clinical Professor, Department of Ophthalmology, The University of Hong Kong
DR. LAI: Hey, hello, everyone. And welcome to this Cybersight webinar. I’m Timothy Lai from Hong Kong. I’m going to talk on two topics today. One is on poll you poi doll choroidal vasculopathy, or PCV, and the other is on retinal complications of myopia. So, polypoidal crises, PCV is a considered a subtype of neovascular AMD. It’s prevalent in Asia. And accounts for 30 to 40% of Asians with AMD. It’s characterized by multiple recurrent episodes of serous hemorrhagic PED and exudative ma cue lop think. You can see here the orange, the serous detachment and the retinal hemorrhage as well. The lesions, they are called the polypoidal lesions. And they are best seen in those indocyanine green as seen here.
So, how do we diagnose PCV? We usually use one of the criteria. And the most commonly used is the EVEREST diagnostic criteria. The first multi-centered control trial for the treatment of PCV. Focused on the reading and center grading of c SLO-based ICGA. And you can see the presence of the ICGA hyperfluorescence within the first 6 minutes after the ICG injection. And branching vascular network, pulsatile polypoidal lesion, nodular appearance when viewed stereoscopically. Presence of hypofluorescent , and I will go through these one by one later on.
So, why is ICG the best diagnostic tool for PCV? This is because the ICG molecule is highly protein-bound and does not leak through the choriocapillaris and will remain in the choroidal vessels. It is better than fluorescein angiography, and the emission spectra allows it to transmit through some hemorrhage and exudates. ICGA has been the gold standard investigation to differentiate poll PCV from typical n AMD CNV. In the early phase, ill-defined hyperfluorescent, and then nodular regions of the branching network. In terms of fundus appearance, these cases have multiple, recurrent, serosanguineous retinal detachment. You can see the orange knowledge. There’s usually a notch within the edge of the PED and.io you don’t have the typical soft drusen in the vascular, and you get the massive sub-retinal hemorrhage. This is another clinical appearance of the PCV. You can see the patient on the right eye. You can see the orange polypoidal region with the exudate and myelopathy. And the right side has the subretinal hemorrhage and therefore you get a scar formation. This is taken from a very good paper from Thailand by Dr. Chaikitmongkol. You can see the polypoidal regions on the photograph. You sometimes get massive sub retinal hemorrhage. And hemorrhagic PED. There’s usually a notch in this hemorrhage, a notch PED. In terms of the ICGA pattern, I mentioned before, it’s the diagnostic tool of choice and therefore you get these polypoidal lesions with this branching network. Here is also, you can see this, there are two polypoidal lesions here. And so with this PED. Another case, color fundus photo showing this large area of PED and subretinal hemorrhage. And you can see the branching that’s the vascular network and the polypoidal regions on the upper edge of this PCV PED. If you use the color, the confocal scanners, you can also get very good contrast in these pictures. And you can see that here the polypoidal lesions showing the early and the late phase of the ICGA. Here another example. You can see these polypoidal lesions can occur as a single polypoidal lesion or in a cluster like here. It’s like a — like a branch of grapes. On angiography, usually the PCV lesion will appear as hyperfluorescence and might be indistinguishable as occult in CNV and neovascular AMD. And classic FA leakage has been described. In the middle, this is a patient with the leakage. And on the right side, you can see the ICG showing the polypoidal region with the branching neovascular network. And on the example, you can see the multifocal leakage which you cannot see the polypoidal lesion very definitely in this case. And another important diagnostic school is spectral domain-OCT. We can evaluate the morphology of the changes in the PCV. And you can see the polyps appearing as an tear your dome-shaped elevation of the RPE layer. And along with the presence of the SRF and PED. And they can be visualized as two reflective layers. And we call them the double layer sign. This is representing the elevation of this neovascular lesion. And a spectral domain-OCT is also very useful to monitor these patients treatment response. With ongoing treatment, we can decide whether to re-treat the patient or not. And we can use the enhanced imaging node to look at the choroidal thickness. And in relatively young patients, many of them have a thick choroid. It’s considered as part of the spectrum of eye diseases. So, just look at some of the SD-OCT features of PCV. You can see the PED which characteristically is a sharp peak, thumb-like, or notched. It can also be a M-shaped with a hyperreflective ring. You can see the double layer sign or thin separation between the RPE and Bruch’s membrane. And pachychoroid, thickened choroid. And you can see the rings. Here again is taken from the paper by the Dr. Chaikitmongkol. You can see what is the definition of sharp peaked PED? If you measure this angle from the edge of this polypoidal lesion, the elevated PED to the RP lay. Anything greater than 70% would be considered as a sharp peaked PED. So, in a typical neovascular AMD picture, you can see on the top here, it’s around 45 degrees of this PED. It’s a fibrovascular due to AMD. And on the bottom, a very sharp peak. Almost 90%. A typical PCV kind of PED. You can also see multi-lobulated or M-shaped and notch PED. Also this double-layer sign and also the hyperreflective ring. So, this is representing the polypoidal lesion. If you look at some of these features, because many centers, they do not have the ICGA. You can still use the OCT to make quite a good diagnosis clinically. So, fundus photo. If you see this notch or hemorrhagic PED, you get an area on the curve of about .77 accuracy with spectral domain OCT, look at the features, PED notch, sharply peaked, hyperreflective ring. About 90%. And two of the four are present, you get about 90% accuracy. Enhanced depth imaging is useful to look at the choroidal, because in the conventional OCT, may mainly focus on the retinal levels. But with the E DI OCT, you can go deeper looking at the choroidal layer. And you can see the choroidal thickness in different diseases. For example, in this study from Korea, they measured patients choroidal thickness in age-related deterioration and PCV and CSC. In PCV and CSC, much trickier control. PCV and CSC, retinopathy are related to the spectrum. And with the en face OCT, we can see that these cases will have some dilated choroidal vessel, a pachyvessel along with the elevation. In order to verify the changes in the OCT as a diagnostic criteria, a group of us led by Gemmy Cheung from Singapore, Won Ki Lee from Korea and myself, we formed this ocular Asian imaging society. And with many experts throughout the world, we formed a consensus for the features and validated the findings. This was published three years ago in ophthalmology. We recommend some terms to standardize the nomenclature. The term on multimodal imaging now for the polypoidal lesions and the branching neovascular network. And then the sharp peaked PED here, and sub-RPE ring-like lesion. And the complex/multiocular PED. The diamond shaped PED. And the branching neovascular network. Thick choroid with dilated vessel. Fluid compartment, you can see the fluid may need sub-retinal fluid. And also, RPE complex elevation on the enface OCT. And for fundus feature, we look at the extensive subretinal hemorrhage or the orange knowledge. And looking at all these nine features and took nine photos, and the best are the sub-RPE ring-like lesion. Second is the en face OCT of the R PE elevation. And third is the sharp-peaked PED. They had an area of the curve from .79 to .83. So, clinically, you can quite reliably use these two to diagnosis your PCV cases without the use of ICGA. More recently, people have also used the OCT angiography to look at this. And you can also use the combination of structure OCT and OCTA to diagnosis PCV. And this gives a reasonable sensitivity and specificity. As you can see here, you detect the flow signal within the polypoidal lesion and you can see that the — both these scans OCTA as well as the enface OCTA can detect the polypoidal and branched lesions. Let’s go for the first polling question. The polling question is which of the following is not a feature suggestive of PCV? So, first one is polypoidal lesion in ICGA. Second is sharp peaked PED in spectral domain OCT. Third is nodular orange subretinal lesion in fundus photography. And the last is confluent soft drusen in fundus photography. You have 30 seconds to vote, please. Very good. So, we can see mostly 80% got it right. So, we do not typically see the lesions in fundus photography. Those are the sign use typically see in the AMD, in the neovascular AMD or even dry AMD cases. But not in PCV cases. Right. So, let’s go to treatment. Why do we need to treat PCV? For example, in this natural study we performed in our Asia population. We looked at 32 eyes of 32 patients with PCV without treatment for all of them for at least 12 months and these patient HHS-wide a mean follow-up of about 5 years. And you could see there was a significant reduction in visual acuity and proportion of patients with 20/250 worse. Increased from 28% to 53%. And the main causes of poor vision included hemorrhage, RPE atrophy or scarring. And that’s why we need to treat our patients. How can we treat them? So, the most simple one, it’s the direct focal lazier and it has been used for extrafoveal PCV. With these patients well away from the fovea, we can use the laser to burn it. There might be damage, vitreous hemorrhage. And the alternative technique is to look for the feeder vessel. But it’s technically very challenging. This is an example of what we used. We used a green laser here and then we applied it to this extra foveal polypoidal lesion. And two months later, you can see this polypoidal lesion completely gone on the ICGA with good improvement in visual acuity. And over 3 years, this was still stable. But there was some enlargement of the scars. If the lesion is well away from the fovea, we can still do the thermal laser. If it’s closer to the fovea, obviously we should not do because it can damage the fovea. What’s the best treatment nowadays? We have two very good randomized control trials providing level I evidence on the PCV. The EVEREST II study and the PLANET study. It’s depending on the lesion characteristic and we can use anti-VEGF therapy, and we also have new agents like, and then the combined treatment. And I will show you some of the results on these key trials. The first one is EVEREST II, a two year study, double-masked, multicenter. And it compared the use of ranibizumab and the primary outcome is to look at the change in visual acuity. And you have other secondary objectives which include looking at the change in central retinal thickness, the regression rate, number of treatments, et cetera. So, the study randomized over 320 patients. Half of them to the combination arm, ranibizumab and vPDT and the other to ranibizumab alone. And by the end of the study, some of the patients were switched to the combination arm because it showed a superiority in terms of using combination therapy. If you look at the change in visual acuity at month 12 and month 24. Both groups did well. Both groups improved the vision with loading dose of treatment. But the improvement was more marked in the combination arm. So, for the patients who receive ranibizumab plus initial PDT, they had 9.6 obtained. And those with only ranibizumab, they gained like 5.5 letters, this is a four letter difference. And for the regression, about 70% better combination year. At about 24 months, about 56%. Whereas ranibizumab, 36% the second year. By doing combination treatment, we can substantially reduce the number of ranibizumab injection. 30% of patients only needed three to four injections in the combination arm compared with 13% for the monotherapy arm. And the median number of treatments over two years, on the 6 for the combination arm. Whereas for the monotherapy, it’s about 12 injections. So, we can reduce the treatment burdens quite substantially. In terms of the number of PDT, 40% had one PDT treatment at the initial onset. How about the other study? The other one is the PLANET study, and it’s a aflibercept. They all had three monthly dosing of aflibercept. And then randomized to two arms. One with active rescue PDT. The other was the sham PDT. But both arms would still be having ongoing aflibercept 2 milligram every four weeks and then extension. And then they would be at the one year, they would be treated as the treatment extends. So, many patients did not receive the rescue treatment because the rescue criteria, they were quite stringent. You can see, if they were only allowed to have rescue treatment if their vision is less than 73 letters and had a substantial visual loss of 5 or 10 letters. And OCT showed new fluids. And if they had ICGA showing active polyp, they could have rescue treatment. ICGA was not performed in all patients at week 12. Only about 17% of patients throughout the study were eligible for rescue treatment. Some patients had a lot of the CST was comparable. But these patients had a lot of worse — the vision to start with. But nonetheless, if you look at the results on the patients’ treatment. Aflibercept plus rescue or active PDT, or sham. They did similarly well. So, about 9 to 10 letters. Whereas the poll you poi doll recursion rate, about 30%. Not as high as you saw with the combination treatment in the EVEREST II study. Number of injections was about 12 injections the first year. And here you can see that both studies gained vision at the end of the study. So, the number of treatments, about 12 injections over 24 months. So, a lot of differences between the two studies. EVEREST and PLANET. EVEREST II, mainly a prompt treatment of the PDT and the onset. And loaded them with the injections and then decided whether rescue treatment is needed or not. You cannot really directly compare the studies. So, at the moment, if you look at a Japanese study, they can still recommend either for PCV cases, you can still do monotherapy or use a combination of PDT plus. But if the vision is relatively good, 0.6 is the kit off, then monotherapy should be considered instead of using combination therapy. nowadays, most doctors because of the issue with getting it in many countries and also the lack of laser machines for the PDT, most places are actually just doing monotherapy for the patients. But patients, because they will have ongoing disease activity with stopping the treatment. So, treatment extend — treatment is highly recommended for the PCV patients. Okay. So, just to summarize PCV. With the rapid improvements in imaging technologies including spectral domain OCT, OCTA, we can make better diagnosis in monitoring our PCV patients. And based on the phase 3, 4 study efforts, 2 and the PLANET study, and you can see the anti-VEGF monotherapy and combined anti-VEGF can improve the patients vision quite well. Okay. Now let’s go to the second topic of today. Which is on myopia. Pathologic myopia in particular because it’s associated with various retina and macular diseases. How do we define pathologic myopia? A globe elongation and a refractive error of at least 6, and axial length of 25.5 millimeter. It’s high he prevalent in Asian populations. Especially in East Asia, around 10% of Asian populations with the disease because excessive axial elongation causes mechanical stretching and thinning of the layers causing the pathology. And therefore you get increased risk of many retinal complications including retinal degeneration. Retinal degeneration and the retina tears predispose you to retinal detachment. Abnormal shape, posterior staphyloma, dome-shaped macula. And chorioretinal atrophy, and myopic. So, previously we did a study? Hong Kong looking at our population with all very high marked patients. 337 patients. In Asia, quite young, 36 years with a mean of 10.2D. And among these patients, 11% of eyes were found to have one or more posterior pole lesions. And after correcting the axial length and refractive error in older age, significantly associated with more posterior pole lesions. And the standard to grade the macular changes is using this PM study group classification. They classify the patients as category zero, no macular lesions. Category 1, tessellated fundus, category 3, diffuse chorioretinal atrophy, and 3 with the patchy, and four with the most severe. And you can have any stage with lesions and cracks and focal spots. Here are some examples of the various categories. This is a patient with a tessellated fundus. A patient with diffuse can chorioretinal atrophy. And then the patchy chorioretinal atrophy. You can see many of the patchy lesions. And finally, very severe macular atrophy. And you can see the vessels because it’s compromised. And with any stage, you can also get associated plus lesion here. It’s the crack, CNV formation and macular hemorrhage. So, more recently the Institute of International Myopia Institute, we also published another white paper looking at the progression of these diseases. So, high myopia, you can get the normal and tessellated. And then you can get the atrophies, and this is a signifying choroidal thing. And it can cause macular — associated with atrophy or the associated macular atrophy. So, in terms of macular complications, there are a few that you should be aware of. Firstly is the myopic traction ma cue lop think with the myopic foveoschisis and you can get the hole type. And then the myopic CNV, these are treatable. And look at myopic foveoschisis first. What is myopic foveoschisis? And you can get the mechanical splitting of the retinal layers in the macula. And in patients, you can see this in up to 34% of patients. And patients can complain of metamorphopsia and blurring of vision. They can cause retinal detachment if not treated. So, the pathogenesis is because of the very elongated eyeball. And then you get the vitreous traction. Causing this splitting of the internal limiting membrane and the abnormal contour and also the retinopathy due to the shape and they cannot adhere very well. In terms of natural history, a study has been performed to look at 29 eyes with chronic foveoschisis. And followed up two and a half years. You can see over these 31 months, 20 eyes, that is about 70% of eyes, can have vision worsening with the remaining 30% had some stable vision. And with this, nine eyes actually developed macular hole. So, six of these actually have foveal detachment prior to the macular deterioration. Surgery was done in 11 eyes and resulted in significant visual improvement.
Another study performed in Singapore. They also look at 50 eyes. Followed with the spectral domain OCT for about 12 months. And you can see that they had different types of morphology. So, entire macular retinoschisis, the photoreceptor detachment, foveal EZ disruption, macular holes, the poorest vision those with the entire macular retinoschisis. And follow-up of about 31 months, 28% had worsening of two or more license of vision. So, we should we perform surgery? Patients could have quite good vision retaining about reduction for many years. But surgery is still indicated because of the potential progression. So, when should we do the surgery? Usually we do it when there is the presence of pre-macular structure. Like attractional DRM or macular traction. Reduced vision or distortion of vision functionally. The patient is quite symptomatic. And if you do the OCT assessment and see foveal detachment, that’s a good indication that the patient needs surgery. For surgery, you can do vitrectomy with or without ILM peeling and with or without gas and oil tamponade. And buckle is performed, and sometimes combined vitrectomy and buckle. Go through the steps. First, the vitrectomy with ILM peeling. For the ILM peeling, make sure you can get complete resolution of the residual vitreous cortex on the macula. That would reduce it due to the pre-macula structure. And removing the still ILM can facilitate the retina to conform to the posterior staphyloma. The result is generally quite favorable. 80% of the patients have improvement after the surgery. So, this is a paper we published over 15 years ago now. You can see it’s more serious, about nine eyes with the vitrectomy. And the peeling. the patient’s vision improved well, 20/80 to 20/50. And 78% of eyes had complete resolution and 22% resolution. Some studies they did not use scans. So, they just performed the vitrectomy and ILM peeling. They classified into two groups. One with foveal detachment, and one with no foveal detachment. And showed 100% success rate after the surgery. And those with foveal detachment gained the best, much higher significant improvement in vision compared with the no foveal detachment which stayed similar. They suggested that surgery should be performed in cases of foveal detachment. This is an example that we operate on. You can see the membrane bran and the foveal detachment. And then the vitrectomy and after peeling, two months later, complete resolution, and vision improved to 20/30 as well. Another series looked at these patients have photo detachment. And macular hole. And found that foveal detachment cases had the most improvement. By the time you had macular hole, no significant improvement in vision could be obtained. That’s why you perform the cases when there’s foveal detachment and not waiting for the macular hole formation. And sometimes we don’t peel the ILM because of the surgical damage and the potential for the formation of a macular hole. ILM peeling can still result in good success per decease. But this meta analysis showed that the anatomical and visual outcomes were similar with or without ILM peeling. But in terms of macular hole formation, because the numbers were quite small. Only about 10 to 20%. But many series did not have many. It remained unclear whether peeling would cause the hole in the macular formation or not. And some groups advocated the use of foveal-sparing ILM peeling. You just peel the ILM around the fovea. Not leaving the central part behind. And so, this will hopefully preserve some of the Muller cells. You can perform it with or without gas. It’s controversial. Sometimes thing with foveal detachment, you can cause issues. I don’t have any experience, from the Japanese group, they do not recommend it these days because of the potential long-term retinopathy. And these patients, if you put something behind it, it can further exacerbate the retinal atrophy. The other condition you have to treat is the myopic macular hole. Because if you don’t treat this, you can cause — it can progress to retinal detachment. You can get vitrectomy, and with the gas and the tamponade and the ILM peeling. And sometimes the ILM repositioning. Macular buckling and scleral shortening surgeries have been performed. But these are close because the choroid is quite thin and you don’t have much tissue because of the elongation of the eyeball. The contour is not correct. Many patients may still need multiple surgeries. So, previously we used vitrectomy and high density silicone oil. We get about 83% of success. But vision remained poor despite a successful surgery. Another study, they looked at the silicone oil. Here 100% with heavy silicone oil. After removing about 87%, standard, about 60% reattachment rate, not removing the silicone oil, 53%. But vision did not improve significantly. Many patients had quite severe macular atrophy. And another study, they used ILM repositioning. So, put the ILM as a scaffold over the macula and then used some autologous blood and found a bit of visual improvement. In another study, with the inverted ILM insertion. 100% success rate in this group compared with some insertion, only about 33% success rate. You can see still controversial what kind of procedure should be performed. Nonetheless, generally we perform vitrectomy and then peeling and injection for the hole cases. And finally, the topic would be on pi myopic CNV. Quite common, occurs in about 5 to 11%. And most common in the CNV patients under the age of 50. In general, it’s the second most common cause of CNV after neovascular AMD. And incidence, it’s around 10% after 10 years. In terms of natural history. Why do we need to treat it? Because these patients generally have visual decline if we don’t do treatment. This is a study done in Tokyo. Because initially about 29% will have a vision of 22 to — worse than 22/100. But by 5 years, increased to 88%, and by 10 years, almost every had a vision of 22/100 or worse. We need to treat the cases. In terms of treatment, how to manage them. We can confirm the diagnosis of myopic CNV and choose an anti-VEGF agent. Ranibizumab, and we have Conbercept. And off-label. Ziv-aflibercept. And one or two doses if they need it. And very few patients, if they have a ongoing large lesion, might consider ongoing doses or treatment extend. And the most important one for OCT. Fundus is important. You can use OCT and angiography. And others are not too essential. So, why do we need all these tests? Because you need to know whether the visual loss is due to myopia or other conditions associated with myopia. That I mentioned before, retinal detachment, dome-shaped macula, staphyloma. Or other atrophy. And look at if it’s due to other causes or not like neovascular AMD or due it a crack formation. We call them simple macular hemorrhage which can resolve on its own. And puncture in the choroidal, idiopathic CMV. These are the differential diagnosis. You see the retinal hemorrhage. It’s due to the crack formation, not due to myopic CMV. And you can the macular myopathy and the hole detachment. The most commonly used diagnostic tool. And in the active CNV shows up as a well-defined hyperfluorescent lesion. And leakage might be subtle, but it might with the only sign of myopic CNV activity. With the use of FA, you can see the leakage and therefore differentiate from other causes of macular hemorrhage. And usually the hemorrhage is very thin. So, therefore myopic CNV would not be masked by this blood. And you can also use the FA to determine the location of CNV. Usually the foveal or extra foveal. And for spectral domain OCT, we use it quite often nowadays because it’s the standard of care for managing these patients. And monitoring the response. In these parents, usually type 2CNV, above the RPE layer. And when you get inactive CNV, you get the hyper-reflective dome. And after treatment, it can cause a scar and you get this hyper-reflective lesion which will cause a shadowing effect. So, people have done studies comparing the use of FA or OCT and they found that it’s the diagnose of CNV can be made in about 68%, OCT alone, 22%, and in both, 16%. There was no sign between active CNV between FA and OCT imaging. The FA and OCT, they really do complement each other. In this case, one of our patients. You can see macular hemorrhage in this highly myopic eye. OCT showed the CNV quite well. And also, there was some other existing pathology. The membrane. And showed the leakage associated with the hemorrhage. OCT-A can be useful and you can monitor these patients. It’s also been incorporated in some of the — the protocol. So, in a study studied in the UK. They looked at the patients who had myopic CNV and underwent OCTA angiography. And found that combining the two, SDOCT and OCTA, you can get a 97% sensitivity. Quite well. Now a days, do SD-OCT and OCTA. And then go for the treatment. But if it’s negative, do an FA to confirm the diagnosis. Now, polling question number two. So, which of the following is not useful for diagnosing myopic CNV? Number one is OCT, second is OCT-A, thirdly is fluorescein angiography and last is Humphrey automated visual field test. We have another 10 seconds. Good. Most of you got that. The others are also quite useful. Okay. So, next, let’s go through the treatments. So, as I mentioned before, without treatment, many patients will have worsening of the vision. And so, this study, again, showed without treatment they deteriorated the vision. In the past, people have done thermal laser and surgical removal. But these are no longer performed because we have better treatment. PDTs, first treatment available. Maintain the patients vision, but not improve the vision. Rarely do it nowadays unless the patient has a contraindication. Most use anti-VEGF agents. Why use the anti-VEGF? We know the level ideas the eye. And we have clinical experience that it can improve the vision. As I mentioned before, we have the first treatment available. On label and off-label treatment. This is a patient who I treated with bevacizumab. And you can see in the CFA, very typical type II CNV. This is the OCT as well. So, gave three injections of bevacizumab. And you can see very good reduction in the CNV on the OCT as in regression in the VA. And improved the vision and didn’t need treatment afterwards. Compared with the previous treatment, the treatment demand is much, much lower. Let’s look at some of the clinical trials. One is the RADIANCE study. A very large study. Looking at the use of bevacizumab. Guided by visual destabilization. These patients had the injections at day one and also month two. Or second, so, just one initial injection. And then looking at PRN treatment compared with PDT treatment. So, you can see that patient with the bevacizumab even at three months, gained for the bevacizumab group, compared with the other group, only about two key letters. And guided by the activity, they had a similar outcome at month six. Nowadays we would guide our patients using this. One injection of bevacizumab and then the patient would do — ranibizumab and the patient did well. The patients in the group, they were eligible to switched and gained some vision. But never quite up to those who were treated early. And afterwards, we also did post-radiance study. Looking at the long-term outcome of these patients. So, initial patients had another three, four year follow-up. And you can see that after the patients exited RADIANCE, they still maintained their vision. So, some of the patients required additional treatment afterwards. And these patients with additional treatment, they still gained vision. Maintained that level that you observed in the exited rate. In the long-term, the ranibizumab treatment was quite favorable. And you can see recurrence ran — not a lot of patients had recurrence. Around 20%. Another study is the MYRROR study, looking at aflibercept. That’s versus sham injection. And you can see in general the aflibercept injection and the as-needed treatment. And then the control and the sham for six months and then eligible to switch to aflibercept. Looking at the patient improvement. You can see primary outcome. Patients treated with aflibercept early, they gained 12 letters. Patients treated with sham, they lost two letters. And at the end of the study, patients treated with aflibercept at the start, gained 13.5, and patients switched to aflibercept, gained 3.9. Some improvement, but a large gap. Again saying you should treat your myopic agents with anti-VEGF agents early. And like the first quarter, last nine months of the injections. So, treatment demand is very low for these patients. One is the SHINY study in China. They used Conbercept and loading doses versus sham. You can see the three injections and then the control group, just sham initially. And you can see the characteristics, baseline, comparable. And very similar, what we saw in RADIANCE and in the MYRROR study. And improvement in vision with anti-VEGF treatment. And good reduction in macular thickness. And four injections. But these patients had loading doses. A bit more injections in SHINY than the other two studies. How about the real world? In the real world, of course, the IRIS Registry conducted by the AAO in the US is the best registry for many of the diseases, including myopic CNV. And they found patients had observation or anti-VEGF treatment. This is one week from the index that they looked at the — identified the case. So, 130 cases here. And you can see the patients’ vision improved from .5 unit to .3. So, on average, about .17, 1.7 lines of visual improvement one year after starting anti-VEGF therapy for CNV. And if you do nothing, no anti-VEGF, they had loss of vision. And most only had one or two injections. Very rarely you needed three or more injections. Myopic CNV, treat your patient early with anti-VEGF. In terms of consensus, we grouped together to form some consensus on what to do. Myopic CNV, try to get it in the active phase. This is when the damage to the photoreceptor causes visual loss. We need the treatment. And once the lesion is getting bigger and they’re already having some fibrosis, even atrophy, then the patient’s vision would not be able to be salvaged. That’s why we recommend patients to be referred to retinal specialists. Someone who can do injection. Inject them early. Do one treatment monthly for a few months and then three months before the first year in case of recurrences. And this is also another consensus we prepared. So, recommendation is that anti-VEGF therapy should be the first line treatment for CNV. And should be one or three doses. Depends on where you are. Largely we tend to give three in, but in a small lesion, one injection is enough. Final polling question. Which of the following should not be performed as a treatment for subfoveal myopic CNV. First is thermal laser photocoagulation, second is intravitreal existrial ranibizumab injection, third is intravitreal existrial aflibercept injection, and the last is intravitreal existrial Conbercept injection. Very good. You should not perform thermal laser. 80% it right. Fantastic. We now have anti-VEGF which is very effective. Just to summarize, myopic and CNV are important sight-threatening complications of pathologic myopia. And we can do various surges for treating MTM. And in terms of myopic CNV, we have good clinical trial data showing anti-VEGF agents are good for CNV and require a low number of injections. Treat your patients promptly and monitor them after the initial treatment. So, with that, thank you very much. And so, just to show you two pictures in my recent trip to Vietnam. Had a very good group of trainees and fellows. So, fantastic experience there. So, thank you very much.
So, we can now have some Q&A. All right. Let’s go over to the questions. Feel free to type your Q&A. So, the first one is that question on how can you determine the cause of subretinal hemorrhages, whether they are dough to polypoidal choroidal vasculopathy, or AMD, particularly when angiography is not available? As I mentioned before, many places may not have ICG angiography. That’s why nowadays we do a lot of OCT to diagnosis. And if you look at the PowerPoint that I just presented with the use of OCT spectral domain OCT, that is, we can diagnosis most of the PCV cases. Around about 85 to 90% by looking at various OCT features. So, the most important one, of course, the subretinal knowledge, and the complex elevation. All these features, if you have two or more of these. And also the other is fundus photo. Look for the orange lesions. And then if you have three or four of these features, then it would be highly suggestive of the patient’s having the subretinal hemorrhage due to PVC. And also look for other patients, of course. If you see the patient having a lot of soft tissues, might be a case of wet AMD, CNV, rather than a PCV case. But nonetheless, nowadays mostly we use monotherapy for our patients regardless of neovascular, PCV, you monitor them after the treatment carefully. And the best outcome is if you can afford the patient to have treatment extended. Because that can maintain a dry macula usually.
All right. Second question is how do I differentiate polypoidal lesions from window defects? So, another very good we. So, window defect, we usually refer to those patients for angiography with atrophy. So, shine the background is coming through. So, polypoidal lesions, we do not define them on angiography. We only define them on the ICG angiography. Because that’s the term that we use ICG angiography. And you can see the polypoidal lesions are those who actually had a knowledge, hyperfluorescence within the first 5 to 6 minutes within the ICG angiography. That’s how to differentiate from a window defect. It’s a finding in angiography due to atrophy. Okay. The other — how common is this disease? So, this disease I think you are referring to PCV because that was a question at 9:11 p.m. And so, it’s relatively common in Asian populations. So, around about 30 to 40% of patients presenting as neovascular MD. In Hong Kong, China, Singapore, Malaysia, Thailand, Japan, Korea, and Indonesia. Even India. They are quite common. And even in the states, in some populations, for example, in those in Hawaii, they also see a lot of these in the Asian ethnic groups. So, if you see an Asian patient presenting as neovascular AMD, think of PCV. That can be about 30 to 40% of them are actually due to PCV. Typical neovascular AMD. All right. Next question is on what is your opinion about macular buckle? Well, my opinion on it is that I follow what the Japanese nowadays are doing because they have been doing macular buckle for many, many years. And they in the last 10, 15 years they have also stopped putting in because they have seen the long-term complications to the patients with high myopia. They have a thin choroid. And you can alter the shape of the staphyloma very well. But you get the atrophy later on. The patient, anatomically they do well, but visually, they do worse than doing some other surgeries. Some of these patients unfortunately we cannot offer them any treatment because the macular hole. We have done multiple surgeries and still failed to close because of this abnormal shape of the eyeball. So, in those cases, even with successful macular buckle, they might not still see too well. We still don’t have very good treatment for these very severe cases. But nonetheless, fortunately, most of the cases are not that severe. So, for most of the myopic cases, with foveal detachment, vitrectomy peeling and injection. Most of them do reasonably well. Okay. So, another question is on the benefits of peeling ILM in myopic macular detachment surgery. So, very good question. So, the benefit of peeling the ILM is that the ILM is a rather rigid structure. After peeling, you can actually see the whole ILM, it’s actually like a plastic sheathe and it can roll up, curl up very significantly. So, after peeling that, it allows you to flatten the retina better. So, and sometimes — some groups have also done using that peeled ILM to plug into the hole as a scaffold so that it can form a seal over the macular hole. So, these are two of the benefits that can — and another benefit is that when you peel the ILM, you are making sure that any residual cortical matter, the very flimsy cortex, they are also vitreous cortex, they have also been removed. And those not caused attraction to the macula. That’s why when people peel DRM occasionally, they would like to peel the ILM so that the residual membrane on top would also be removed and that will reduce the recurrence rate and increase the success rate of these myopic macular detachment surgery. Right. Another question. So, can we diagnosis a case of PCV without performing ICG based on the OCT features. And, of course, if you listen to the lecture, certainly. If you would like to further reference. So, go to the APOIS paper that we published back in Ophthalmology in 2020. And that will show you the list of features of an OCT that can be suggestive of PCV. And most of the time clinically nowadays I would say the majority of clinicians, they are doing the OCT along to diagnosis PCV. It’s only when you really need to diagnosis it for scientific studies or if you plan to do photodynamic therapy. In those cases you will need the ICG angiography. Because to apply the therapy, you need to have the ICG to determine the spot size covering the polypoidal region and the branching network. And, of course, patients who are having regular anti-VEGF injections and not responding to the anti-VEGF therapy, you want to know what’s going on. In those cases, you would like to perform the ICG angiography and might see the polypoidal lesions. It if you want to reduce the treatment burden, you will also do another. But we have more powerful anti-VEGF agents. You might consider switching them to the stronger agents to see if it works for the patients. All right. Another question. Very interesting. So, can PCV occur in older patients? Of course. PCV can occur at any age. So, younger ones even like in their 40s. The youngest one I think I saw was 39 years old. In older patients, you can see it in 80 or 90-year-old patients. So, any age it can occur. But generally these patients with PCV are a bit younger than the traditional. So, we’ve done studies in Hong Kong comparing typical AMD, PCV and the other subtype is retinal wrap. And you can see the PCV is around the high 60s for the patients. Typical AMD mid-70s, and RAP patients, low 80s are the mean. And they tend to be younger and thicker. Another question, in what age can we use anti-VEGF? Good question. In general, for patients with any form of CNV, we can still use anti-VEGF. So, the youngest one I had, it’s an idiopathic CNV. The patient was only about 8 or 9 years old. Just make sure they do not have any systemic factors in terms of older patients, of course. Because a very small potential of systemic risk. So, you always ask for any myocardial infarction recently or cerebrovascular recently. And younger patients, especially female, we also have to be female because of the potential pregnancy risk. So, patients who are female and pre-menopausal, we would also ask for their pregnancy history. Although it’s not an absolute contraindication. But, for example, myopic CNV. They can occur in 20-something, 30-year-old lady. If they’re pregnant, you might consider waiting for a few months until the patients deliver the baby so that you can inject the anti-VEGF a bit safer. Usually first or second trimester I’m a bit more concerned. Third trimester, if they’re really threatening the patient’s vision or the other eye is really bad, you have to discuss with your patients and decide. And of course, for the youngest patient who is need anti-VEGF therapy are those newborn with retinal — retinopathy, IRP. Those patients use a reduced dose of anti-VEGF in those patients. Any age can have anti-VEGF agents.
So, another question is sometimes CNV spontaneously healed without any treatment? So, yes. It’s possible. Back in the old days. But then once it becomes fibrous and you get a big scar. And the patient’s vision will drop quite considerably. That’s why nowadays with anti-VEGF therapy quite readily available, we should treat these patients with anti-VEGF agents. It’s the best therapy for them. Especially for myopic CNV, the treatment demand is very low. You only need one or two injections in the majority of patients. All right. Another question. On FA and ICG. So, can you do them at the same visit or two separate visits? So, very good question. So, in most of the system, we would have both of the angiographies available. Even the flash camera or the confocal scanning laser or thermal scope, they would have the same — the different set of filters inside within the same machine so that you do not need to do them on separate visits. So, a lot of times we just draw up a FA first and look at any leakage. If there’s a feature suggestive of PCV or other pathology that ICG-A is helpful, then we would also ask them to do the ICG angiography at the same sitting so we can see both the retinal and choroidal circulation well. Another indication for ICG and PCV is, of course, the choroiditis. It has been useful in some cases. So, another question on how effective is autologous transplantation of color reside and R PE in CNV? I would say it’s still very experimental stage. And if you look at the previous macular surge studies, the outcome was just not as good as what we get in anti-VEGF therapy. Because a lot of times you get actually visual worsening instead of visual improvement. And even if you have transplanted successfully, the underlying process will sometimes cause further CNV development and you will still end up patients needing anti-VEGF therapy. At the moment it’s still not a mature treatment, I would say. So, for CNV, the current therapy is still using anti-VEGF. Okay. Another question. Very practical, good question. The recommendation for phaco in MTM, macular neuropathy patients. I also do cataract surgery and for these myopic traction neuropathy patients. If it’s mild thickening of the macular and no foveal detachment, I would do the phaco. And they would recover and see quite well afterwards. But if they already have foveal detachment or significant myopia, then I would do a combination therapy. For those age 50 or above. I do a vitrectomy, or peeling and injection to the phaco, and implant the lens. For myopic patients, usually if they are already scared, no active lesion. Then those patients I would still continue the phaco. Just do cataract surgery for them. But obviously, avoid the fluctuation of pressure during the surgery. Because that might sometimes cause some macular hemorrhage. But if the patient is having active myopic, it can show the active leakage with the sub retinal material, inter-retinal fluid. Those cases I would do the anti-VEGF injection first and treat them. And then once they are stable, at least three, four months later and then would consider doing cataract surgery. Okay. Another question is how can we parentheses ongoing increase in axial length? Okay. Very good question. So, unfortunately, with the prevalence of all the electronic gadgets and close work in these days, it’s very hard to prevent it. And so, that’s why we have childhood myopia programs in Hong Kong. Hopefully with the use of various new glasses. So, those focusing glasses and also with the use of low-dose atropine, we can prevent some of these patients having increase in axial length. And the question on the peripheral degeneration. Which, of course, I didn’t have time to cover. So, do you carry out laser preventive measures? So, depends on the patient. So, if the patient is having the retinal holes, for example, at the other eye already have retinal detachment, strong family of retinal detachment, those I would do a laser. But for peripheral degeneration, not symptomatic. I usually just keep on observing them. Having regular dilated fundus examination once a year. For those high — depends on how high the eye is, if they’re minus 6, but if they’re minus 10 or minus 15, see them more regularly and warn them of new symptoms. If they see a shadow, then they should come to see you immediately. Okay. Sorry. So, another question. So, myopic C NV with glaucoma. I’m not a glaucoma specialist. But I think these patients with high myopia, they are prone to have glaucoma. And if in doubt, refer to your glaucoma specialist to deal with that. With anti-VEGF injections, sometimes causes a spike in the ILP as well. That’s why in some of the glaucoma patients, if they have severe optic disk damage, might consider chamber paracentesis. And consider using some auto-glaucoma drops to lower the ILP quicker after doing the injection. So, another question is how often do you see vitreous hemorrhage after intravitreal in PCV cases? Not often at all. The rate if you look at clinical trials is 1% or so. In some of the biggest studies, even in Luminous, the biggest study conducted as a pharmaco study, the rate is very low. Some risk factors cause the vitreous hemorrhage. For example, you have multiple polypoidal lesions or large PED or a patient on some anticoagulant. Those sometimes can result in bleeding. But it might not be due to the anti-VEGF agent. Because without treatment sometimes the bleeding is actual worse. Sometimes with the break new vitreous hemorrhage, you have to do vitrectomy to resolve them. Okay. So, second to last question. So, how accessible is anti-VEGF in terms of cost and rural regions? So, very, very good question. So, depends on your country, of course. And nowadays it’s more accessible in some places because of the availability of — you have it in some countries. The price has gone down substantially. And, of course, you can also use Avastin which if you don’t have a compound pharmacy like in Hong Kong, we use it just before an injection. We group all the patients together and share them. That will lower the cost quite substantially. But with the use of — the cost will hopefully decrease. Okay. And I think that’s all. So, thank you once again for joining this webinar. And so, send me an email. If you are interested in anything on today’s topic. And I hope to see you in the future. So, thank you very much.