Lecture: Evidence-Based Treatment Update on Age-Related Macular Degeneration (ARMD/AMD)

DR. AHMAD: Hello, everybody, and welcome to the Cybersight presentation about the age-related macular degeneration. My name is Imran Ahmad. It I’m at the Khyber Teaching Hospital in Peshawar, Pakistan. I will start sharing my screen and we will start with the presentation. So we’ll talk about the age-related macular degeneration. The age-related macular degeneration, it’s the leading cause of visual loss in elderly population. As the name indicates, it’s an age-related disease in the macular region. And one in eight above 60 years is affected. It’s rarely below 50 or 55 years of age. And as the age advances, the age-related degeneration increases. The progression is about less than 1% if the age is below 55 years of age. And it is more than 15% if the age is beyond 80 years. So, the visual loss is more common in US age-related macular degeneration, but the dry type is more common than the — type of macular degeneration.
The risk factor, the most common risk factor as the name indicates, is the changes that take place in the macular region with the aging that disturb the architecture of the macular region with the aging process. That is affecting the photoreceptor layer, the Brux membrane, choriocapillaris are affected. The age is non-modifiable, the non-modifiable risk factor. The most important modifiable risk factor is smoking. And because smoking is related to the progression of age-related macular degeneration. It increasings the chances, triple or quadruple and it’s entirely dose dependent. Because it’s with the age-related macular degeneration. Hypertension is responsible for the region in the macula. The cardiovascular diseases, again, it affects the choriocapillaris which are responsible for the perfusion of the retinal tissues. And the level of the anti-ox dents. Because the oxygen stress increases with the low level of anti-oxidants, it increases the risk factors. And also exposure to UV lights, diabetes, and cataract surgery, and genetic factors also. With the aging process, just to go through the aging changes that take place within the macular region. Because the macular is having high oxidative stress, it’s the most important part of the retina involved in the metabolism, and converting the light, and coming persistently to the macular region, and from the visual impulses to the brain. The photoreceptor, that’s the most important, and the outer end of the photoreceptors that are continuously degraded and taken away by the normal functioning of the retinal pigment epithelial cells. And then with those the outside layer is the Bruchs membrane. With the aging, the permeability of the Bruchs membrane increases, and there are micro changes that take place within the photoreceptor layers and the retinal epithelial cells. They cannot pump all the products set aside because of the metabolism, the macular region, to divert it to the choriocapillaris and it changes. There are changes taking place with the aging. The normal physiology of the macular region, the outer segment, is continue by the retinal pigment epithelium cell, it goes through the Bruchs member and drains out. With any abnormalities, and this is complex, all of these cells are closely related to each of these. And if there is a defect, and one with the photoreceptor layer, the retinal pigment epithelium layer, the Bruchs member, it changes. As I mentioned, the age is the most important risk factor. Smoking, genetics, hypertension, diet, obesity, UV exposure, cardiovascular diseases, UV exposure, all are part of the macular degeneration. And what happens with the epithelium pigment cells? And toxic and oxidative stress play an important part in this. Initially when the retinal pigment epithelium is with the aging, it can not pump out from here to the choriocapillaris and to the Bruchs membrane. And the products and the passage of time, and composing of lipoproteins and phospholipids and protein and the production of this. And then with the passing of time, the pumping action is not there due to the aging, these cannot perform the function normally. The size of the drusen increases. If it’s small, the person is not symptomatic. It’s small, but it is a sign that the disease will progress with the passage of time. And ultimately the passage of the retinal layer, thickening of the Bruchs membrane, and then a vicious cycle starts, there’s hyper perfusion, and — their role, they came into play, and actually the photoreceptor is lost, the retinal pigment epithelial cells are lost. There is hyper perfusion of this region because of the oxidative stress, and the increased factors are released, and responsible for the vessels from the choroidal side, and reaches into the sub retinal space. So, basically, if it is like this, then it’s not there, it’s basically the atrophic form of knack layout degeneration, and then there’s the subretinal space, and it changes to the type of age-related macular degeneration. And the vision loss is affected by this in comparison with the dry type of macular degeneration. And then we have to understand the pathology of the drusen as well. As I mentioned, these are the excretions. And the retinal pigment epithelial cells here, it is unable to pump out all of these secretions. And the hydraulic function of the retinal pigment epithelial and the Bruchs membrane is lost. The Drusens between the pigment epithelial cells and the Bruchs membrane. It leads to the pigmentation of the cells, and it’s the soft appearance due to the drusen and the space. Soft Drusens are mostly associated with the progression to the rare type — the neurovascular type of macular degeneration. And then hard drusen is with the dry type of macular degeneration. And then one is the dry type, atrophic time of MAG layout degeneration. And when it becomes atrophic, it regenerates. You can see there’s not a retinal pigment epithelial cell, it’s lost. And there’s a spot formed in the macular region. Because this is not dry type, so there will be no neovessels, no leakage. Whereas in the neovascular type, there’s leakage from the neovessels. The normal vessels cannot leek, but the neovessels can leak, and sometimes maybe hemorrhages, exudations, and sometimes atrophic is formed. Basically the age-related macular degeneration is by the disease study, ARDS. No age-related macular degeneration, no or small Drusens, it’s category 1. In category 2, also called age-related macular degeneration,ing there be multiple small Drusens. Actually going back to the size of the Drusens, smaller if it is less than 63 micron, and intermediate, between 63 and 124 may cron, and large if the size is more than 125 microns. In the early AMD, multiple small, few intermediate Drusens are there. Meaning small is less than 63 microns. And some Drusens have having size between 63 to 124 micron, that’s categorized into category 2. The category 3 is the intermediate type of age-related macular degeneration, and numerous intermediate Drusens and at least one large drusen. One Drusen size should be more than 125. There’s significance for this classification as well. The fourth one is advanced age-related macular degeneration. That’s category 4, geographic atrophy in one way, and neovessels are formed in the macular region, then it’s classified as category 4. The importance of the classification, with atropic type or neovascular type of macular degeneration, and in that area, basically, it was based on this classification. No treatment is indicated for the — if there is no AMD, means if there are no Drusens, or very small Drusens, and none is given for the early as well. The antioxidant treatment is not in the first two categories, category 1 and 2, but if it is indicated in the category 3 and category 4 in which there is advanced age-related macular degeneration and in the intermediate macular degeneration. Because in the ARDS study, actually they showed if there is no AMD or early AMD, it can not prevent the progression to the advance the stage of macular degeneration, whereas in the intermediate and advanced stage of age-related macular degeneration, the antioxidants were there. Category 1 and 2 is not an indication for treatment. Whereas in category 3 and 4, we have to go for the treatment. Again, there can be nothing or you can find small Drusens. Then with the passage of time the Drusens increases. Some large Drusens, intermediate Drusens, lead to geographic atrophy, stage four, or new cells in the stage 4 which is indication for treatment. Clinical feature, definitely because it’s in the macular region. In the macular region, the patient will be experiencing the blurred vision, central scotoma, the central part is affected, or metamorphopsia, and changes as well. And most of the time the complaint of the patient is like this, whatever I’m looking at, I’m unable to appreciate that thing. Looking at the clock, the central part of the face is missing. Involving the macular region, it’s lost, and providing the sharp drusen or the central vision. As I mentioned, one is atrophic, one is neovascular. I will be coming to both of these one by one. Atrophic age-related macular degeneration, you can have some pigmentation in the macular region. The vision of the patient will become comparatively good. And then Drusens formed, small size Drusens, and with the passenger of time, these Drusens will come together and lead to the geographic atrophy. On the one side, this is the normal OCT scan. The normal OCT scan, as you can see, the Drusens were here. It has caused elevation of the retinal pigment epithelial cells, that is pigment epithelial detachment. And again, it depends on the number of Drusens. There can be a lot of Drusens in the sub-RP space leading to the appearance, and all of the retinal pigment epithelial cells seems to be elevated like that. Again the atrophic scars come together, and going to the center, and the vision will be there and the pericentral vision is affected. And sometimes in the central macular region, and there will be underlying there. And this is the geographic atrophy, you can see all the macular regions up to the periphery within the arcade, all this area is atrophic. That is the geographic atrophy. You can see the choroidal vessels here. And sometimes there’s the dry type can change into the wet type of macular degeneration if they penetrate the Bruchs membrane and come into this region. And you can see the retinal pigment epithelial cells are there, there is loss of the photoreceptor layer, and loss of the epithelial cells, it’s not there. And thinning of the retina. On OCT you can see the back vein and the light will penetrate because of the absence of the melanin pigments in the macular region. Typically there’s fundus geography and dry type of visual macular degeneration. Whenever the dye is going through the choroidal vessels, whale the choroidal vessels are seen, and it will give defects in these patients. The management, the most important area in the age-related macular degeneration is the dry type. Whether it’s the dry type or wet type of age-related macular degeneration. And the most important thing is the patient education. Because it’s an irreversible disease. As the name indicates, it can be related to the age. The disease cannot be reversed, but we can slow the progression of the disease. And need to counsel the patient. It’s important to regarding the risk factors, specifically the modifiable risk factor, the smoking, the control of the cardiovascular diseases, hyperlipidemia, hypertension, the risk factors for the age-related macular degeneration. So, the page is — and second is the compliance of the patient with the treatment because the patient has to get treatment for a longer period of time. I have to mention we’re here in the ARDS-related, actually the antioxidants were given for years, for round about nine years. The patient has to take the antioxidants for a longer period of time. And the indication for treatment, as I already mentioned, that if the patient is in the category 3 or 4, not in the category 1 and category 2 of age-related macular degeneration as specified by the age-related eye disease study. So the indication for treatment is only category 3 and 4, but not 1 and 2. And category 1 and 2, if there are small Drusens, no Drusens, small Drusens with intermediate size Drusens, treatment is not indicated and we need to follow the patient. And only have to counsel the patient with the risk factor for the progression of the disease. If the patient is in category 3, that’s intermediate. And if there’s CME, that is cardiovascular choroidal vessels, then we have to give antioxidants to the patient. And then the one, the age-related study 2 protocol we are following. And the age-related eye disease study, the treatment was Vitamin C500 milligram, Vitamin E400 international units, beta carotene, XING, and what happened was 44% of the patients, there was progression of the disease, with the same treatment, whereas with the antioxidant treatment, there was 34% of the treatment. And the impact of the treatment and there was 23% of the patients were not progressing. And then in Age-Related Eye Disease Study 2, they replaced the beta carotene associated with the smokers, and replaced with lutein and zeaxanthin. Category 3 and 4, take the supplements, as I mentioned. But category 1 and 2, the supplements are not indicated. The evidence didn’t show that the antioxidant can stop or slow the progression of the disease. We have to prescribe the medication in category 3 and category 4 only. The lifestyle modification for the patient is needed. And Amsler needs to be given. The Amsler grid to the patient. We have to counsel the patient, they have to check vision with the Amsler weekly. Use the eyeglasses with one eye closed, and both eyes checked separately. And if the patient experiences any new changes, metamorphopsia, lines on the grid or anything, they have to report. If it is stable, there is no need. But if it is not stable, the patient has to report. As I mentioned, the dry type of macular degeneration can change that into the wet type of the macular degeneration, which is more dangerous than the dry type. It is basically just to show you that the Drusens are not always associated with the visual loss. These Drusens are familial-Dom innocent Drusens and it is not associated with the visual loss. The second type of age-related macular degeneration is the wet type or exudative or neovascular type of age-related macular degeneration. As the name indicates, neovessels will be there. And keep in mind that the normal vessels will not bleed. But the neovessel will always bleed and leak, leading to the edema, and the fibrous tissues, and ultimately leading to the formation of scar. The choroidal neovessels are there, and they can be type I, type II, or type III. Type I, the choroidal vessels passes and passes through the Bruchs membrane. It breaks through and reaches into the sub-RP space. If the neovessels are not crossing the retinal pigment epithelial cells. It means it is the type I. Previously it was called the classic type of age-related macular degeneration. I’m coming to that. But basically that classification was focused on the fundus geography before the OCT in ophthalmology. Now on the basis of OCT, we can classify that the neovessels just passes through the Bruchs membrane and reaches into the sub-pigment epithelial layer, it’s the type I choroidal vessels. If it crosses the retinal pigment epithelial cells, passes through the Bruchs membrane, not in the space, and goes into the sub retinal space, then it is called type II choroidal neovascularization. Sometime sit passes through the Bruchs membrane, the RP not going to the space. But passing through the retinal layers, that’s also called retinal angiomatosis. It’s the type III choroidal neovessels. It’s very easy. Just remember if the choroidal vessels are in the subretinal epithelial space, it’s the type I. Crossing the retinal epithelial layer but in the subretinal space, not proliferating, it’s type II. And proliferating within the retinal layers, it’s type III. Investigation, basically, the OCT, nowadays that is the gold stand with the OCT angiography. And the fluorescein angiography has decreased with the passage of time, we have other modalities for investigation like the OCT and OCT Angio. It can give a lot of information, including the type of neovessels. Whether it’s in the sub- RP space, subretinal or intraretinal. And the second thing is occipital OCT Angio. We can have the help of OCT Angio if we are suspecting any other diagnosis, but sometimes for the leakage, and if you are not sure about the proper diagnosis, go for the fundus fluorescein angiography. We cannot repeat it, there are some risk factors involved, and giving the fluorescein dye to the patient. That’s why nowadays we are going with the non-invasive procedures. And the fundus fluorescein angiography, as I mentioned, you can have the geographic atrophy because of the loss of epithelial cell little in the macular region. And it’s exactly like that of the window. If there is no light outside the window, you will not be able to see the window. If it’s coming through with the light, testimony be black. And it will be shown like this, there will be choroidal flush. And because of the lack of pigments, loss of RP in the macular region, then the — is here. The second thing is, and if there are any neovessels, it the leak. And with the passage of time, the leakage increases. There are hemorrhages and causes a block flow. Something is blocking the background. With the fluorescein angiography. And the classic and other type of age-related macular degeneration, going back to the FFA era before the invention of the OCT actually at that time our diagnosis used to be based on the fundus fluorescein angiography. And basically the classic type of age-related macular degeneration used to be leakage from a specific area, from a well-defined area. And there is an upper type, the leakage was from ill-defined area. Diffuse leakage from the ill-defined area. Now the classic type is the type II. Meaning the sub-retinal classification, and classify it to be the type I, that is the sub-RP choroidal neovessels. Then there can be hemorrhages because I already mentioned, if there are the neovessels, and the layers, and there can be hemorrhages leading to the block fluorescence by the hemorrhages, and hyper fluorescence of the leakage area. Again, the classic VNV, you can see the well-defined pattern with the passage of time and increased intensity. And the occult type, I mentioned, leakage from the ill-defined areas. Not a specified area, diffuse leakage. Because the ideal treatment for the choroidal neovessels are for the wet type, used to be photodynamic therapy. And in the photodynamic therapy, the layer needs to be applied to the macular region. But nowadays, we are giving the anti-VEGF, the gold standard and the treatment of first line for the choroidal neovessels and the age-related macular degeneration, mostly dependent on ocular coherence Tomming my. Again, you can see there, the hemorrhage, the area by the leakage. So, OCT is the most common modality nowadays we are using for the age-related macular degeneration. You can exactly classify the type of age-related or the type of the choroidal neovessels CNV, type I, type II, or type III. Initially, if there are Drusens formation, you can see here, the macular compared to dry, no edema in the macular region. You can see only defects and the integration of the retinal photoreceptor layer. Meaning something is pushing the photoreceptor layer, but these are very small. And you can see irregularities in the retinal pigment epithelial layer. Then with the passage of time, if there is loss of the photoreceptor layer, loss of the RP, and thinning of atrophy of the photoreceptor layer, along with that, thinning of the macular region. You can see, you will not be able to see the photoreceptor layer here. Neither the retinal pigment epithelial cells. And again, hyperreflective foci, there can be fibro– type of macular degeneration. There can be neovessels leading the cystic spaces, you can see disintegration of the retinal pigment epithelial layer. Again, you can see the PD, regular, that is the fibrovascular, and there is no edema, and you can see which type it will be. You can see it’s sub-RP, just below the retinal pigment epithelial layer, mean it’s the type I. You can see here edema in the macular region as well. Again, the vision, you can see here as well. And this is the type of epithelial detachment, a large epithelial detachment and cystic fluid surrounding the retinal fluid epithelial detachment. Again, there is fibrous tissues. There is cystic edema within the retinal layers, and you can see over here with the hemorrhage as well, the macular edema, the hemorrhage from the neovessel size, and it will lead to the edema. Such type of CMD choroidal vessels, if the it’s there, we can treat these patients with anti-VEGF. And I will go over the various types of anti-VEGF available. But after the treatment, is some scar tissue is formed. And that’s why the role of counseling is there in age-related macular degeneration, they are expecting the normal vision. But it depends. When you started the patient on anti-VEGF therapy. The earlier you start the patient on the anti-VEGF therapy, the better the visual outcome. Started on anti-VEGF or the patient presented and the diagnosis is late, and anti-VEGF was started late, the prognosis is guarded and the scar will be formed in the macular region. Again, you can see the PD is there, there are some cystic spaces within the — these neovascular area. Another investigation modality is the OCT Angio, it’s a procedure and depends on the flow of the blood within the vessels. You can have the averages of the superficial layers of the retinal plexus, the deep layer of the retinal plexus, the outer layer and also the choriocapillaris. And again you can have the scan of the OCT of the macular region. You can see the edema along with the OCT Angio. In the outer layer of the retina, it’s perfused by the choriocapillaris by diffusion. There should be no vessels in the outer layer. If there is vessels in the outer layer, it’s choroidal vessels, and breaks the Bruchs membrane and came into the sub-RP space. Again, the same photograph, you can see outer — the outer retina is supplied by diffusion. Usually there are no neovessels. These neovessels have grown from the choriocapillaris into the — break into the Bruchs membrane and reaching up to the retinal layers. The fundus changes are usually there can be hemorrhages, there can be edema, a scar in the macular region. Again, you have to correlate it with the age of the patient. There can be hemorrhages in the macular region as well. And ultimately if the diagnose is delayed, the treatment is delayed, then usually a scar is formed in the macular region and usually the visual problem is guarded. And they can use some vision, and some remaining vision is there. And we need to counsel the patient that they will not go blind, but the center vision is bought it’s degenerated. And the treatment for age-related macular degeneration is important. The first thing is the patient education. We need to explain the disease to the patient. As I already mentioned that it’s an age-related disease. So, we can reduce or stop the progression of the disease, but we cannot completely cure the disease. So, we need to explain it to the patient. The second important thing is adherence to therapy. The patient needed to adhere to the therapy because the patient might need a lot of anti-VEGF injections. There are various protocols. According to that the patient can be treated. But everything needs to be explained to the patient that it’s not a once and done procedure, but we have to follow the patient again and again and again. And the patient, we can stop the anti-VEGF at some time, but we can re-start the anti-VEGF again if they got the edema off the worsening of the symptoms of the patient. And the realistic expectation of the patient. It can not be restored. We can reduce or we can preserve the vision that is there because of the edema. But if the scar is formed in the macular region, actually the patient cannot be treated at that stage. Then the importance of the treatment. If the patient is not going for the treatment, the remaining vision will be lost because it’s a bilateral disease. Not — it’s affecting the one eye, but it will ultimately affect the both eyes. It can be asymmetrical. The vision and one can be good, and the other can be worse. But usually it’s a bilateral disease, and the other eye will be progressing in the same fashion. Here decision making is very much important. The doctor has to, or the treating physician has to explain everything to the patient, and with the consistency of the patient, it should be started. And the age-related macular degeneration historically, the laser was applied. The important one was the thermal laser in which the laser was applied to the patient. And the second was a photodynamic therapy, a laser. The photodynamic therapy, because with the thermal laser, actually the chances of collateral damage are the damage to the macular region was much more. The reoccurrence was much higher. And in photodynamic, it was used and the dye that was used, and then the laser used to be applied and the laser has to be taken by the neovessel, which is having the dye. So, basically the collateral damage was reduced in photodynamic therapy. It was a gold standard back before the invention of the anti-VEGF injections. After the invention of anti-VEGF injections, now very rarely the photodynamic therapy is used. After the introduction of the anti-VEGF era, it has revolutionized most of the treatment options in ophthalmology. Most of the diseases can be treated with the anti-VEGF injections. The first anti-VEGF injections were introduced back in 2004, was pegaptanib, then ranibizumab, and all of these types of anti-VEGF were introduced. And now going towards the prolonged acting anti-VEGF because the drawback to anti-VEGF is that it needs to be repeated. The half-life of anti-VEGF is up to 30 days and most of the injections we need to repeat after 30 days. Some are long-acting. But actually we need anti-VEGF for very long which is having very long half-life. So, and the 2004, the pegaptanib was introduced for the age-related macular degeneration. And approved by FDA, then ranibizumab by FDA, aflibercept, and then aflibercept HD in 2024.
and then PDS is introduced back in 2025. But amongst all of these anti-VEGF, the most commonly used is bevacizumab because of the price value, because it’s the most cheaper one. And it’s not only even — it is the most commonly used anti-VEGF worldwide. About 65 to 70% of the population who need anti-VEGF are dependent on bevacizumab. Because in most of the countries, anti-VEGF is not provided by the — so the patient has to purchase it for themselves. Especially in the developing countries. Most of the patients are dependent on the bevacizumab. It’s not approved by the FDA, but there are many cases that show it’s similar to the aflibercept. the most common one is bevacizumab. And I mentioned all of these. But then after the VISION trial, it was approved by the FDA in 2004, pegaptanib. It was not a very successful drug because of the reason that the pegaptanib was active only against the VEGF 165, but not effective against the other forms of VEGF A. The most important factor is A. And pegaptanib was only active against 165. Basically it was also given for some time, but when the other anti-VEGF were introduced, then the use of pegaptanib was reduced. Actually, with the invention of the anti-VEGF, it changes the treatment paradigm of AMD completely. Because previously, actually, most of the treatment options were just to slow down the progression of the disease. Or stop the progression of the disease. Whereas anti-VEGF is not only associated to stop the progression of the disease, but actually after the introduction of the anti-VEGF in ophthalmology, it was again changed because for the first time it was associated with the improvement and the visual acuity that was lost with the macular degeneration. And this was with all types of anti-VEGF, and all the mabs, every type of anti-VEGF that is associated with improvement of vision. So, that was the vision — after VISION trial was introduced, pegaptanib was introduced. But because it was limited efficacy, it was abundant. And then ranibizumab, and so many were on this, and the MARINA trial, and it was in the macular degeneration, and age-related macular degeneration and the vessels. And it was compared with the photodynamic therapy in ANCHOR trial. The number of injections can be reduced, but they were more effective in comparison with the photodynamic therapy. PrONTO study then was done, and the HARBOR trial, and also I will coming to the ARCHWAY trial because it’s the latest one. And the HARBOR trial, and the protocol was followed. There was a difference in the protocols followed for the injection of anti-VEGF. And PrONTO actually, its approach was adopted for that. That if the patient treated with ranibizumab, and come with the worsening of the disease, and there’s the neovessels again, then the patient was injected again. And the HARBOR trial, the number of injections reduced through the passage of time. But whenever they shifted from the monthly injections to the PRN or the treating extended protocol, what happened is the visual acuity was comparable to the monthly injections, but not exactly like the monthly injections. The vision dropped in the treatment protocols. Then aflibercept 1 and 2 trial, and compared, and shown to be non-inferior to ranibizumab. And PULSAR trial is the latest trial with the high dose is used, that’s 8 milligram. And then the brolucizumab was in 2019. It was approved if I diabetic macular edema. And offered in the HAWK & HARRIER trial. It’s associated with vascular occlusion and vasculitis. And it showed that these complications, about 6% of the patients with the aflibercept group got these. And again, the use in age-related macular degeneration is reduced because it is associated with retinal vasculitis and uveitis. And the Faricimab, came a couple of years back after the TENAYA & LUCERNE trial. And showed that the longer duration of anti-VEGF can be given. It used to be treated. And after three months the injection can be repeated. Whereas in 70% of the patients, it can be repeated after four months. TRUCKEE trial, it was gone for Faricimab, and the loading dose was not there. It’s not completed as yet because they’re waiting for the results of that. But actually, the initial results show it is comparable. Whether you give the loading dose to the patient, that is monthly doses and then shift to the quarterly, or give one dose of faricimab and then change to weekly injections. And the bevacizumab, I mentioned the off-label uses. The ABC trial, and the CATT trial. ABC trial, with the photodynamic, and CATT trial, it is compared. And then IVAN that was done in the UK. The same trial, the trial that is like the — and the GEF AL trial. And all these showed that the bevacizumab is like those of the other anti-VEGF injections. Like the diabetic macular edema, whether we can go, and the age-related macular degeneration, along with anti-VEGF, actually the results are still inconclusive. And it is not a recommended use for macular age-related degeneration, because it’s associated with cataract and pressure, but it’s not proven yet. Then how to treat these patients with age-related macular degeneration? How to give the injections? One is the monthly injections. Most showed all of these injections showed that the monthly injection is associated with the reduction in the macular thickness and improvement in the visual acuity. The other is as-needed approach. If the patient is having, again, the disease, if there is edema, there are now vessels, re-formation again, then we have to treat the patient again. And the third one is three phases. And one is we have to treat the patient until the macula is dry. There are no neovessels, no photoresponse to anti-VEGF injections. Once that is established, then we have to increase the duration between anti-VEGF, if four weeks is given, then shift to eight and then ten weekly and then 12 weekly. We need to increase the duration until the patient has the reoccurrence of the disease. And then some edema at 18 weeks. It means that we have to slightly reduce the duration from that. We can injection every 16 weeks. And if we can treat the patient and extend the duration. Problems with the anti-VEGF, all anti-VEGF is the number of injections. Most of the time the patient is asking this question, how many injections I will need? Actually, we don’t know. It depends on the macular thickness, the edema and the choroidal vessels. And unless the macular edema is there, or the patient is responding to the treatment, we have to inject. Poor compliance. The patient is not coming again. And especially in developing countries, come off for a few months and then come back. Healthcare burden, it’s having the burden, and the resources. Under-treatment, again, because of the reason that the patient is noncompliant. And real world outcomes sometimes most of the people are saying that it’s missing. It’s not there. The recent advances because the anti-VEGF are associated with having to inject monthly in these patients. So the only thing now in the anti-VEGF, we need long-acting anti-VEGF. Most of the patients are reluctant to be injected every month. We need the duration to be higher. That’s a long-acting anti-VEGF are needed. Faricimab can be given 16 weekly, and the same with Eyles ED. And the PULSAR trial showed it can be repeated after three or four months. And that’s 8 milligram of aflibercept. And introduced Susvimo, and the archway trial was done for that. We have to replace the port within the pars plana. And release for up to 6 months. After 6 months, the port delivery system needs to be refilled again, and again, it will work for the 6 months. And it’s an office-based procedure. But again, the delivery system was created back in 2022, but associated with some dislodgement, and the manufacturing defect with the system, the poor delivery system. It was withdrawn by the pharmaceutical company. But again, it was reintroduced in 2025. So, again, that is the six month delivery system. The patient doesn’t need to be injected monthly. The gene therapy is nowadays the most for the age-related macular degeneration patients. Associated with longer anti-VEGF release. Basically what happens in the gene therapy that the — usually the genome associated, that is manufactured in the laboratory with the required gene and then it is injected. Either in the supra choroidal space. And nowadays, there is no conclusive trial, the trials are going on, and multiple trials under way. It can be injected intravitreally. And what happens that the — this gene is introduced and this then it is taken up by the retinal pigment epithelial cells. And the retinal pigment epithelial cells, what it will do, the anti-VEGF factory. Release anti-VEGF for a longer period of time, for months and years. So, still the trials are going on for the gene therapy. That is — associated vector is manufactured because it is the harmless. And then it is introduced into the eye, and then the supra choroidal space or into the intravitreal or sub retinal space, and taken up by the retinal pigment epithelial cells and then transcribing into the messenger RNA, and the need for monthly injections are not there. These are the various screens for trials that are underway or going still or not gene therapy. PRISM trial, AAVIATE trial, AMOSPHERE trail, and looked at the ranibizumab. And then the ASCENT trial. Only reserved for the complication. Of the sub-macular hemorrhage, we can give an injection and ask the patient to be in the prone position so that it is dispersed — the hemorrhage is dispersed from the macular region. But usually, reversed for complication. Or sometimes if the patient develops scar, the scar is formed in the macular region, we have to go for the visual rehabilitation. That’s the optical aids, high plus glasses, hand magnifiers, telescopes, electronic magnifiers to make the life of the patient easier. And smartphones and screen magnifiers are there. And the treatment summary, the non-neovascular, that’s the dry type. And early age-related macular degeneration, observe the patient. Intermediate, meaning category 3 or 4, go for the protocol, antioxidant treatment. And neovascular, start on the therapy, and the better and all of these are available, aflibercept, and also the off-label use of the bevacizumab. So, the take home message is ask the patient to check themselves with the Amsler grid. Any distortion of the vision or any new symptoms, we have to — the patient has to report again and come to the treating ophthalmologist. OCT is essential in diagnoses and follow-up. And we have to treat based on the OCT, whether it’s dry and the scar is formed. And anti-VEGF is the first line treatment in all these patients. And early treatment is vision saving. But if the treatment is delayed, the scar will be formed and usually the visual recovery will not be there. Thank you very much. And now we have a poll and I will answer some of the questions that you people have asked. And there will be five questions in the poll.
This is the first question. A 72-year-old man presents with gradually progressive blurring of vision in both eyes. His best-corrected visual acuity is 6/9 in each eye. Fundus examines reveals multiple small hard crew sen and a few medium-sized drusen in both macula. With no evidence of choroidal neovascularization. According to the recommendations, the most appropriate management is — AREDS2 antioxidant sub he mentation? Intravitreal anti-VEGF injections? Observation? Omega-3 fatty acid supplementation, or Vitamin A supplementation. The next question is about 40% of — 42 observations. It’s very close to the antioxidant, that is 40%. But AREDS2 is basically for category 3 and 4 macular degeneration. It’s not indicated for the category 1 and 2, so we have to observe these patients. And if the status changes to category 3 and had, then you have to start antioxidants in these patients. Next question: A 64 years old woman is diagnosed with neovascular, exudative type of age-related macular degeneration. The retina specialist discusses available intravitreal anti-VEGF agents. Which anti-VEGF agent has a dual mechanism of action? Aflibercept? Bevacizumab? Breakpoint reslizumab, faricimab, ranibizumab, and which has the dual function? Waiting for the answer. So, 25%, 26%, the highest, again, is for the faricimab, that’s having the dual action. With the anti-VEGF action and also the 2. The next question is 75-year-old man intermediate age-related macular degeneration asks which lifestyle factor is most strongly associated with progression to advanced age-related macular degeneration and should be modified to reduce his risk. Which of the following is the most important modifiable risk factor? Diabetes mellitus, diet low in antioxidants, hyperlipidemia, cigarette smoking, ultraviolet light exposure? Which is the most related to age-related macular degeneration among all these five. Very good. The cigarette smoking is directly related to the progression of the disease. And that is the dose-dependent. The number of the — it depends on the number of cigarettes smoked per day. That is a 67% correct answer. Question number four, a 76-year-old woman presents with a two week history of metamorphopsia in her left eye. Her best-corrected visual acuity is 6/18, OCT demonstrates sub-retinal fluid, macular neovascularization with no significant fibrosis or geographic atrophy. Which is the most appropriate management? Observe for three months with repeat OCT, intravitreal anti-VEGF therapy, perform focal laser photocoagulation, start oral corticosteroid therapy, recommend AREDS2 supplementation alone? Which of the following can you most recommend to this patient? 66% of the answer is correct. That is intravitreal anti-VEGF therapy. As I mentioned, the earlier you start the patient on anti-VEGF, the better the outcome. But keeping in mind the neovascular type, how do you know that? The subretinal fluid is there. So, 67%, the answer is correct. Last question. A 78-year-old man presents within 24 hours of sudden, profound vision loss in his right eye. Fundus examination reveals a large sub-foveal hemorrhage secondary to the neovascular. OCT confirms a thick sub-macular hemorrhage involving the fovea. Which of the following is the most appropriate management? Observation, intravitreal anti-VEGF injection monotherapy, pneumatic displacement with intravitreal therapy, immediate panretinal photocoagulation, urgent — if there’s macular degeneration in the region, how can it be treated among these five options? And definitely that subretinal is from the neovascular AMD. So 58%, the correct answer has been given, that is pneumatic displacement with intravitreal tissue plasminogen activator. Because of the time constraint, I was a bit quick. But for the hemorrhage, give the anti-VEGF gas and spine position, prone position to the patient so that the blood isn’t displaced with the macular region. So, I will go to the questions.
Yes. ARMDs is a mitochondrial disease? The various types of the changes that have taken place and the age-related macular degeneration, one of them is the mitochondrial changes in the age-related macular degeneration. Definitely the protein synthesis changed. The age-related macular degeneration is having an effect on that as well. Prognosis of age-related macular degeneration, again, depends on when you started the patient on therapy. What is the stage of the disease or diagnose? The early you start on the anti-VEGF therapy in the age-related macular degeneration, the better will be the outcome. Education is very much effective, as mentioned in this patient because it’s a lifelong disease. Usually all the diseases if had which you will have a lot of follow-up, you need to properly educate the patient. That we have to the risk factors should be controlled. The patient — whatever you can do, like if the patient is having cataract, we need to go for the cataract surgery. The cataracts, again, a risk factor. Whatever you can do in these patients, you have to do that. Whatever is possible. You have to remove the cataracts in these patients. The duration of antioxidants in age-related macular degeneration, following the protocol for nine years. If you ask me how long I’m giving the antioxidants. I usually say you have to take these lifelong. The lifelong duration, the better the outcome. Again, the follow-up depends on the patient. Like if you are treating the patient, we need to repeat the OCT three months. Usually we are giving the anti-VEGF injections like that and then we need to follow the patient again with the OCT. And if you think there is edema again, and the patient is responding to the treatment, the vision of the patient is improving, the macular edema is improving, keep going until there is a response. And two injections, and the further improvement in the macular thickness, stop the anti-VEGF injections. And actually, in the ARD ES2, there is no — of omega-3. Yes, exactly, and the sub-continent countries, the compliance issues because the patient has to pursue it for themselves and as I mentioned, most of the patients in the developing countries or the sub continent are dependent on the bevacizumab. And the bevacizumab is having certain problems with the bevacizumab. It’s not easily available nowadays. The second problem is with the complication associated with the bevacizumab. All these factors are there. Retinal — actually, it’s a type of — that is the type 3, the neovascular age-related macular degeneration. If the neovessels are growing within the layers. Quite a long questions. The time is short. Okay. C SR and the retinal pigment epithelial detachment, is usually dependent because CSR is not an elderly age disease. You can have it. But usually the differentiating point is quite obvious, and the CSR, you will see the clear photoreceptor layer, the retina will be elevated. And whereas in the age-related macular degeneration, you will have something from the choroidal side to the edema and you will see the epithelial cells that will be disturbed. Which — I think it might be the antioxidant. Definitely as recommended by the AREDS2 protocol, it can be given. Self the C3, and the anti-inflammatory, yes, exactly, this is the new treatment options that is going on. And it’s given for the patient. Actually, you can stop the treatment. As I mentioned, if the patient is not responding to the treatment, no further decrease in the thickness, it has regressed. It’s up to the patient and the doctor has to communicate to the type of protocol they want to follow. The PRN, the extent of the protocols. And the macular regeneration, and it was between diabetes and the studies have been done to prove this. Actually, for the — you cannot give anti-VEGF injections for the Drusens. Actually it is for the neovessels you can treat it. And that’s the reason and the geographic, if you’re not treating it with the anti-VEGF injections. If the patient is not responding to one type of anti-VEGF injection, then you definitely, you can switch it to another type of anti-VEGF injection because the molecular structure of the anti-VEGF injections are different. So, if the patient is not responding to one type of anti-VEGF injection, you can change the type of anti-VEGF. For geographic anti-VEGF, the treatment is guarded. You cannot treat these patients, you can give the visual rehabilitation, because you cannot reverse the disease. If the patient has high spike anti-VEGF injection, definitely you need to reduce the intraocular pressure. That’s because of the high intraocular pressure. And that’s you have to give a break into the chamber. You have to go for the parasynthesis. Yeah, exactly, definitely. The and subretinal hemorrhage, definitely, it will compromise the prognosis. Stem cell treatment, again, it’s like the gene therapy. It’s still — but the guidelines are not there. That has established its treatment. Definitely role of the optometrist are not there. And all types of macular degenerations, and all the types — the role is there, and counseling and making an understanding with these patients. Protocols, no specific protocol there is. And there are various types of protocols followed in anti-VEGF injections, PRN, again, you have to discuss it with the patient. The risk factors. Prolonging the duration of actions. Laser is actually not recommended nowadays. The gold standard is anti-VEGF injection. The laser is associated with the worsening of the vision further, actually. CNV, you cannot observe the CNV. As I mentioned, the patients are started on the treatment, the earlier, the better will be the outcome. Gene therapy is still going away. But as I mentioned, the trials are there. The trials are there. But actually the recommendations are still not there in the recommendation and the guidelines. Again, we have to give anti-VEGF injections if the patient is having macular edema due to the AMD. The complications, definitely it’s there, if there is — the dye, it is treated with severe allergic reaction, bronchospasm, pale color of the urine, you cannot repeat it. And sometimes the complicate of electroshock and take place. I think the time is there. We don’t have any further time. So it’s all from my side. Thank you very much.