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This podcast provides a review of some of the key highlights from the Controversies in Modern Eye Care meeting held in April 2023. The program is designed for those who did not attend the live meeting and to help reinforce learnings for those who did.



 This transcript has been lightly edited for clarity.

At the present time, we really have no idea of what causes geographic atrophy, but a lot of attentions being played to the alternative pathway in the complement cascade, as everybody knows, there's three complement pathways. There's the classical, the lectin, and the alternative pathways. There is evidence drusen and in other histopath pathologies that there are complement factors that are involved in drusen, also in the pigment epithelium. There are certain complement changes that will potentially cause these changes to progress. So a lot of attention is being played in the alternative pathway. There is one drug, Annexon, that's being used in the classical pathway. It has some rationale because it's down-regulating C3, but from a different angle. C3 unfortunately, or fortunately, I guess, is the commonality of all three of the pathways, the alternative, classical, lectin pathway. But there is some evidence that C1q, which is found in the classical pathway, will have a role. It does play a role in synapses. It's also found on drusen.

Most of the work is being done in trying to reduce the alternative pathway from even starting. So down-regulation of the alternative pathway is the goal from almost all these drugs. If you start the alternative pathway and it goes through from C3 to C5, all the way to C9, you get what they call apoptosis. So the little cells at the edge of your atrophy begin to have holes, pores put into them, and the cells die. So by treating and trying to reduce the progression, we're hopefully going to reduce the apoptosis that occurs as the final event. So there are many different factors that are being looked at. We have factor I, factor B, factor D, all which down-regulate the complement system. Factor D happens to be a oral medication very similar to lampalizumab, which failed. We have factor I, which is a gene therapy that also down-regulates the system.

Factor B down-regulates the system. Well, there's also the ability to put in complement factor H that may be not present and some patients, and if they can do that, may slow it down. There's a new company that just started. There are some good factors that stop neovascularization from occurring on a genetic basis and they're being placed into the eye and hopefully can reduce progression. But the two major areas are inhibition of factor C3 and C5. C3 is a drug known by Apellis. This drug has been approved by the FDA and showed a fairly significant improvement in the extrafoveal geographic lesions. The extrafoveal lesions basically grow faster and they grow faster, and by reducing them, you can hopefully stop the lesions from growing into the center of the fovea and losing vision.

In fact, in their study, they showed about 27% reduction in these extrafoveal lesion growths, and they recently, just a few weeks ago at ARVO presented that if patients are 250 microns or greater from the center of the fovea, that those patients at two years had five letter better vision than they did in the group that was in the sham group that wasn't treated.

They also have shown that the lesions by visual field tend to not grow as much and you save off more retina. Lesions that are sub-foveal tend to grow at a slower rate in general, and it's only about a 16-18% reduction in the growth rate in that. There's no free lunch in medicine. There's always safety, which is the biggest concern that we have. We've had very excellent drugs recently for treating AMD, but because of the side effect profile and the safety, have never really been utilized to any great degree. The safety is good, but there was about 8% of patients that did go on to developing wet macular degeneration. Inflammation was about 1.5%. There's a small incidence of infection, but that goes along with almost every drug you put into the eye. The C5 is the next drug that will probably be approved.

It is basically, I think in July or August is their PDUFA date. So we'll know in July or August if the approval comes forward. But they should be approved. They have had two phase three trials that both showed statistically significant improvement, whereas in the Apellis drug, it took the C3 inhibitor, it did take 18 months before they started to show an improvement in one of the trials. And at 24 months, both trials were clinically and statistically significant. C5 is downstream from C3 and again, blocking it will decrease the ability for C5b to go on to activating the MAC complex at C9. Another drug that's being tested right now is CD59. It's a drug that actually, CD59 is a natural occurring protein that is in the eye. It goes up when you have AMD and if you can down-regulate that... I'm sorry, it goes down when you have goes down when you have wet AMD, and if you raise that, it will be a natural inhibitor of the progression.

It's a gene therapy. So one and done. Also has been shown to reduce progression of geographic atrophy, again, by the fact that it stops the progression to the MAC complex, it doesn't allow it to form, but we have a lot of unanswered questions. What starts the complement pathway? Is it amyloid? Because amyloid is found in drusen? Is that what stimulates and causes the pathway to begin? Do we have to treat forever? Can we treat just acutely and stop the process? How long do we have to do it? Is it forever? Is this something that we have to do forever? Or once you get the patient righted and you're not having any further inflammation in that pathway, can you back off? And would combination therapy be a more benefit? You've got a C3 inhibitor and a C5 inhibitor both showing about 27% decrease in the extrafoveal lesions.

If you put them together, would that equal an improvement? If you added C3 to CD59, would that cause a bigger improvement? And those are things that'll have to be worked out in the future. Certainly, gene therapy or longer-acting delivery systems are going to be the answer to this. It's not very sustainable to give monthly or even every other month injections to these patients. And the other thing that I'm really amazed about is the number of patients who have dry AMD. When you look at autofluorescence or look at their OCTs or look at their photographs, have geographic atrophy present. It's a lot larger population than I originally thought.

So first, you can have direct damage, which is through the membrane attack complex, which directly targets the RPE cells, and you can also have the indirect damage, which is to the photoreceptor cells where you get that abnormal protein deposition, which directly leads to the mortality of photoreceptor cells.

Evidence supporting the contribution of the complement system to progression of AMD and GA has accelerated the development of therapeutics targeting complement protein C3 and C5. Drugs being investigated include avacincaptad pegol, which inhibits C5 and C5 cleavage, pegcetacoplan, which prevents C3 activation, ANX007, which inhibits C1q, and GEM 103, which controls the complement cascade. Let's listen to Dr. Boyer review these agents.

At the present time there are a number of companies that are investigating the complement pathway as a means of slowing down the progression of geographic atrophy. The thought being that the geographic atrophy occurs and progresses due to dysregulation of the complement system. We don't know what starts it. We don't know if it's started by amyloid, oxidative stress can start this, but there are a variety of different causes that activate the complement pathway. Why the complement pathway? Because a lot of complement factors that are being investigated are found within drusen, and drusen are a hallmark of dry macular degeneration. We also can see that complement factors that are involved in genetics also play a major role.

So if we go to the GATHER 1, 2 trial, which is a C5 inhibitor, basically at this time it's PDUFA date or the day that the FDA has to announce whether they'll allow us to use it or not or approve it is in late July, early August, and it probably will be approved because they've had two 12 month phase three trials that both showed an improvement. In this trial the patients had have to have extra fovea lesions, meaning that the area of geographic atrophy was not centered and was not under the center of the fovea. It could be one micron away, but that was considered non-central involvement. And in that case, in the first GATHER 1 trial, there were about a 27% reduction in progression. In the GATHER 2 trial, it was much more modest, about 16 to 18% reduction.

They were both statistically significant. And when you looked at the GATHER 1 trial data over a long period of time, 18 months, that held, and we don't have the long-term GATHER 2 data. In the second year of the GATHER 2 trial, 50% of the patients went to every other month, and some continued on a monthly basis. Now, there are other differences between the trials, but the safety of the C5 inhibitor was excellent. They had no signs of uveitis. They had a very small incidence of conversion to wet macular degeneration, about 6%.

They seem to have excellent response. They've showed a reduction in the three line loss of vision by patients being treated over the period of time. So we don't have that drug available yet, but at least for non subfoveal lesions, extrafoveal lesions, this appears to be a good alternative. The drug that has been approved recently is a C3 inhibitor by a company called Apellis. It's called SYFOVRE. And this drug acts within the complement system and is central to all the complement pathways. There are three complement pathways. There's the classical, the lectin, and the alternative, and they all meet at the C3 and then go on to C5. And the C3 blockage eliminates C3b from activating the alternative pathway and allowing it to not go to the MAC complex. They've done two trials, DERBY and OAKS. The OAKS trial was positive at 12 months showing an excellent reduction in vision.

The DERBY trial did not meet its primary specified endpoint, but at 18 months, both of them did, then at 24 months the results were excellent. For the extrafoveal lesions, which were about one third of all the lesions in their trial, they showed about a 27% reduction, very similar to the C5 inhibitor I just discussed. They also, however, had a very large percentage of patients who had the lesion under the foveal area, and those the results again, were positive compared to the sham and as well in growth. However, the growth rate was much less, in the range of about 16 17%. The growth rate was significantly decreased. In their trial again, the safety was good. There was slightly a higher incidence of inflammation, though the inflammation was mild and was treated with topical steroids. Also in addition to that, there was about an 8% risk of developing the wet MAC degeneration, having exudative form of Mac degeneration, that form.

There also had eight patients in the trial that went on to developing ischemic optic neuropathy, which seems to be a puzzle that nobody has been able to figure out. There was one patient, I think, in the GATHER trial, and there was one patient omalizumab, which was a very large trial. So this showed a definite change that's been investigated, and two neuro ophthalmologists that are world renowned could not find a correlation, and they found that all the patients had a disc at risk. They all had some other vascular episodes at a similar period of time, whether it be hypertensive crisis or some other change, and felt that this was based on that. But that is still something that needs to be discussed. There are several other complement factors that are being evaluated all again, to slow down the process of the alternative pathway. There's factor B, factor D, factor I.

There's patients who are receiving a CFH. There are also people that are now treating and trying to improve the genetics by giving proteins, or I'm sorry, giving the genes that are positive that actually can overcome the negative genes. There's one in the classical pathway called C1q that's being blocked that they feel is important. It plays a role in synapses and it's also found on drusen, so there is some reason to do it. By blocking it it does reduce C3 further down. Now, as you go down the complement pathway, you eventually end up at C9. And C9 is the MAC complex. It's composed of 5, 6, 7, 8, and 9, and it causes a pore formation, which causes cell to rupture and die. CD59 is a natural occurring protein that reduces the progression. It's found to be decreased in patients with macular degeneration.

And by gene therapy they can add CD59 as a protective mechanism. This protective mechanism may reduce the progression of the geographic atrophy and also reduce the progression of the wet MAC degeneration. So this also is being studied. There are a number of other drugs not in the complement pathway that are being studied to hopefully reduce the onset of the problem. One of them has to do with macrophages and trying to reduce the macrophages from becoming active and activating the complement pathway. Inflammasome are another substance that will cause the activation of the complement pathway and is being treated way upstream to hopefully stop the complement pathway from being activated. There are a number of other factors that are looked at. We know that our mitochondria go down as we get older, but in patients with macular degeneration, it goes down even more in the eye. So several companies are looking at treatment to try to improve the mitochondrial function over a period of time.

And as it improves the mitochondrial function, hopefully it will improve the low luminance vision, the poor vision that we get at night or just age related macular degeneration causes patients to have more difficulty with night vision. Reading needs more light. Driving at night is not very easy to do for patients with macular degeneration. So there are a number of other factors that are being evaluated to try to reduce the onset of the alternative pathway, and also to try to slow it down and hopefully in the near future, some combination of these will give us better results than we have today.

Visual loss associated with advanced GA affects many aspects of patients' lives. Daily functions like household chores become more challenging. Patients may engage in fewer social interactions and may be isolated from family and friends. Let's listen to Doctors Boyer and Macdonald discuss how GA affects patients' quality of life.

Geographic atrophy is an area of loss of the pigment as well as the photoreceptors that lie above them. So everywhere that you have an area of geographic atrophy, you actually have an area that's a blind spot or a scotoma. And obviously as a scotoma comes into the foveal area, patients lose the ability to read, drive, see people's faces clearly. Prior to that though, in both dry macular degeneration as well as wet macular degeneration, patients begin to have more difficulty with night vision. They have a lot more difficulty. They may come in to see you and they're 20/20, and the biggest complaint is, they can't read anymore. Doctor will say, well, you're 20/20. I gave you some reading spectacles, you should be able to read. The biggest problem is the loss of the ability to see. They need a lot more light and they have a hard time driving at night.

They don't feel comfortable driving at night. And even though their vision may be 20/20, their dark adaptation really suffers very early in the course of this condition and continues on. So it would be wonderful to have a drug that would improve that because that's the major complaint that I hear when I see the patients in the clinic. These patients come in and they've gotten the best spectacle correction possible, and sometimes they are 20/20, but still have bitter complaints about reading and everything.

I remember one patient specifically when I told them to buy a light that goes over their shoulder or to get a Kindle, and the patient with the light came back and said, I can read. I can read. It was like a miracle, just having more light and the Kindle has been a big boon. I think patients who want to read and try to read, the Kindle with back lighting is much better than a lot of the other machines that are out there to allow them to read. So I think that it really makes it very difficult for patients to drive and to see people's faces clearly. And again, depending on where the scotoma is, it can be devastating if it's in the center.

It affects it drastically. First, you can have direct decrease of vision. So the visual impairment can affect everything that would require detailed vision. So reading, self-care, detailed vision. And it can also affect contrast sensitivity, which is being able to see shades of gray. So looking at something that wasn't high contrast, very black on white, for instance, looking at facial features of somebody or expressions or navigating in dimmer illumination. So this can lead to a decrease in self-care and activities of daily living, which then can make somebody feel like they are more dependent on others, and that can directly lead to decreased social interaction for people. And decreased social interaction is obviously going to lead to an impact on mental health for these individuals. So it affects them very severely.

Low vision aids and vision rehabilitation services may be especially helpful for patients with GA. Among individuals with low vision, an estimated 90% have useful residual vision that could be optimized from rehabilitation services. Many patients are unaware that these low vision services are available. Doctors Boyer and Mac Donald outline these services.

I think one of the things that we as physicians and eyecare professionals in general, really don't pay enough attention to is the wonderful advances that have been made in low vision. It's very frustrating for me as a doctor for many, many, many years to not have a treatment available for these patients, many of which are very active and except for their dry macular degeneration, geographic atrophy, really want to do things that are in good health. They want to travel, they want to do whatever they can. Some of them are professors and they like to read and they want to continue reading. So I refer a fairly large number of patients to low vision specialists because there are a lot of devices out there, and there are more to come. There are a lot of devices, unfortunately are very expensive, but there'll be glasses that will magnify and will be able to help them read, be able to read to them if they can't read.

There are certain devices that can actually read to them. You can take your iPhone and blow it up also. Just if you were shopping and you couldn't read a label, didn't know how much something costs, you can take a picture on your iPhone and just blow it up and be able to see what the price is so you don't go expecting a $15 item and it's $150 item. So I think that that low vision specialists really help the patients a lot. They teach them little tricks. In the home what they can do, they teach them about navigation. You won't see very many of the patients come in with a white cane, even though they may be legally blind from macular degeneration. It just doesn't happen in my experience. So they have to be very careful when they're outside. My mother, as I indicated earlier in the conversation, had severe macular degeneration, and I took her to a wedding.

My wife was out of town. My sisters were going somewhere else, and I realized that just going down an escalator was difficult for her because she couldn't see where it started and where it ended. Going to the restroom, everybody's got fancy restrooms, little things that sometimes I have to look three times to make sure I'm going into the correct one because the little models that they have on the door are sometimes questionable when I look at them for a while. So I think that there's so many things that low vision can help, just extra lighting. When you go to read a menu, they'll be embarrassed to pull it out. But I send a lot of patients to get low vision, and I think the low vision devices in the very near future will improve greatly.

So when somebody has a vision loss, supplementing that by going to a low vision specialist, looking at what your vision is and how much magnification you need or filters or lighting to help somebody improve their quality of life and daily living tasks is important. A low vision doctor will look at various assistive technology devices or regular optical devices to assist somebody, and they may even do specific training for the patient and have adaptive strategies for them, as well as being able to coordinate with all the other eyecare professionals and other interdisciplinary professionals to help the patient navigate this condition.

This podcast provides a review of some of the key highlights from the Controversies in Modern Eye Care meeting held in April 2023. The program is designed for those who did not attend the live meeting and to help reinforce learnings for those who did.

Advances in treatment for geographic atrophy

The FDA comments in the CRL relate to proposed labelling language, not safety, Astellas said in a press release.

US FDA issues Complete Response Letter for avacincaptad pegol (IZERVAY) 

The data showed a reduction in the GA lesion growth rate of 15.3% versus placebo from 6 to 24 months and a slowing in GA growth rate of 13.4% from baseline to 24 months.

Alkeus Pharmaceuticals announces topline results from SAGA trial on GA treatment

Study authors defined hyperreflective retinal foci as “isolated punctiform elements of small dimensions, 30 μm or smaller, with intermediate reflectivity (similar to that of the nerve fiber layer) and without a shadow cone.” 

Study suggests that small hyperreflective retinal foci may represent local neuroretinal inflammation

Enrollment complete of phase 2b of SIGLEC study to assess safety and efficacy of AVD-104 for GA secondary to AMD

By identifying progressive GA earlier, primary eye care providers can make timely referrals and save patients’ visual function.

Contemporary care in GA: Practice patterns are evolving

Dr. Carolyn Majcher emphasizes the importance of early diagnosis and setting clear expectations for preservation of vision for patients with GA

AAOpt 2024: Early detection and thorough imaging are the key to vision preservation in geographic atrophy

At the 2024 American Academy of Optometry meeting in Indianapolis, Indiana, Carolyn Majcher, OD, FAAO, describes optometrists' crucial role in the early identification and management of geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD). Recent advancements in treatment, coupled with the importance of timely intervention, make it imperative that we equip ourselves with the necessary knowledge and tools to detect GA in its earliest stages. In a collaborative discussion with Steven Ferrucci, OD, FAAO, Majcher, a professor and director of residency programs at the Oklahoma College of Optometry, highlighted the significance of early detection and referral for patients with GA. 

Majcher emphasized that the newly approved intravitreal complement inhibitors, while not restorative, can effectively slow the progression of the disease, allowing patients to maintain their vision and quality of life for longer. The key, as Majcher explained, is to identify high-risk patients and initiate a comprehensive imaging protocol. Patients with large-sized drusen and pigmentary changes are at an increased risk of developing late-stage AMD, including GA. By utilizing multimodal imaging techniques, such as optical coherence tomography (OCT), fundus autofluorescence, and near-infrared reflectance, we can detect the early signs of GA before it invades the central fovea and significantly impacts vision. Majcher stressed the importance of not waiting for GA to progress to the point of visual impairment before referring patients to a retina specialist. 

Patients with extrafoveal or non-centered GA, typically at least one disc area in size, are ideal candidates for the newly approved intravitreal complement inhibitor therapies. These treatments, while not restorative, can slow the progression of the disease, preserving precious visual function and improving the patient's quality of life. 

Equally crucial is the need for patient education and setting realistic expectations. Patients must understand that the goal of these therapies is to slow the progression of GA, not to improve their vision. By managing their expectations and emphasizing the importance of regular monitoring and treatment, we can empower patients to be active participants in their care. As primary eye care providers, we have a responsibility to stay informed about the latest advancements in the management of GA. By mastering the techniques for early detection and establishing strong referral pathways, we can ensure that our patients with GA receive the timely and appropriate care they deserve, ultimately preserving their vision and enhancing their overall well-being.

Videos

Dr. Carolyn Majcher discusses her 2024 AAOpt talk on imaging techniques and emerging therapy for geographic atrophy.

Conference

Dr. David Chin Yee describes how to spot early signs of geographic atrophy and explores promising new therapies that may slow progression and improve vision.

EyeCon 2024: What optometrists need to know about geographic atrophy

At EyeCon 2024, David Chin Yee, MD, presented a talk entitled, "Geographic atrophy (GA): What every optometrist should know." In his presentation, Chin Yee discusses educating healthcare professionals on recognizing GA through imaging tools like fundus photography and OCT, highlighting symptoms such as decreased reading speed and difficulty in low light. It emphasizes the importance of early detection and frequent monitoring, recommending reevaluations every three months, and mentions emerging therapies targeting complement inhibition and gene therapy that may slow progression or potentially improve vision in the future.


Hi. I'm David Hutton of Ophthalmology Times. The Ophthalmology Times/Optometry Times EyeCon 2024 event is taking place at the Hilton Fort Lauderdale Marina on September 27 and 28, 2024, At the event, Dr. David Chin Yee presented "GA: What Every OD Should Know." Thank you so much for joining us. First, tell us about the key points of your presentation.


Thank you for having me. The key point is helping to kind of educate how to suspect the patients with geographic atrophy, what imaging modalities and tools are out there to kind of help to identify the findings that we would classically find ... going over and reviewing whether it's fundus photography, optical coherence tomography or OCT, or using fundus autofluorescence. One, again, to identify these lesions and also use it as a tool to educate patients on what the symptoms may appear as, and also be able to kind of educate the patients and what geographic atrophy actually is. We also briefly go over, you know, what geographic atrophy is and how quickly it progresses, making sure that it's understood that, unfortunately, it's a relentless, irreversible disease process that, thankfully now, for the first time, we have new treatment options which serve to slow down the progression, right. And it's important to understand, unfortunately, we don't have a way to reverse it. We're not stopping it. But the idea is, slowly, you know, to slow down the progression of this devastating disease process, which we now know as geographic atrophy.


What are the most critical signs and symptoms that ophthalmologists and optometrists alike should look for detecting the early stages of GA?


Yeah, you know, it's not similar in some of macular degeneration. What we look for, usually, is that the patient will note loss of central vision, specifically identified on the Snellen visual acuity. But patients with GA, a lot of times, they will notice findings a lot sooner. Specifically, their reading speed can be diminished, right. And so, a lot of our patients with macular degeneration, unfortunately, they also have difficulties with hearing and so they rely heavily on subtitles. And they will find that with the subtitles, their reading speed is decreased. So, they're not able to catch up and read the subtitles before they disappear. So that would be one finding. The other issue is difficulty in low light settings. So, their lights, low luminance or ability to read in low or dim lighting has been noted to be decreased, and that is also something that they will identify and notice. So, if they go to a nice restaurant, it's a candlelight dining, they will have the need to want to take out their flashlight or their phone to make it brighter for them to be able to read or see what they could have seen years prior before having this problem.


What role can optometrists play in monitoring disease progression in GA and how often should they be reevaluating patients?


Yes. So again, which we touched on, is having some of these findings or identifying these lesions, whether it be on OCT, or on fundus photo or fundus autofluorescence. These patients first need to be identified, know that they have this problem, and then be monitored a lot more frequently. Routinely, macular degeneration patients, we would follow up 6 months to once a year. Now, with patients having geographic atrophy, we like to tell them, see them at least every 3 months.


Are there any emerging therapies or technologies on the horizon for GA that both ophthalmologists and optometrists should keep their eyes on?


Yeah, thankfully, you know this is the first class of medication that we have focusing on complement inhibition to slow down the progression. But we do have other treatments — some that are going to be subcutaneous, some in the form of gene therapy — that look to be promising. And the hope is, with these newer treatment and technology, will be able to maybe stop or even reverse or improve vision in the future.

At EyeCon 2024, Dr. Adam S. Wenick led a symposium on geographic atrophy, covering diagnosis, FDA-approved treatments, and key clinician considerations through case presentations by Dr. Leonard Messner.

New treatments in geographic atrophy from detection to intervention

Adam S. Wenick, MD, PhD, chaired a symposium on geographic atrophy (GA) at EyeCon 2024, focusing on the diagnosis, monitoring, and FDA-approved treatments for GA. The session with Leonard Messner, OD, FAAO, also included case presentations that highlighted key factors for clinicians to consider when selecting appropriate treatment options.

 
We are joined today by Dr. Adam Wenick, who is among the faculty at this year's EyeCon conference, September 27th and 28th in Fort Lauderdale, Florida. Thank you for joining us. We're so delighted to talk to you today. I understand you're going to be chairing the featured symposium regarding geographic atrophy (GA). What can you tell us about what attendees can expect to learn at this year's symposium?

 
Thank you for having me. In this symposium we're first going to review the diagnosis and monitoring of geographic atrophy, as well as some other aspects of age-related macular degeneration, including neovascular age-related macular degeneration. And then we'll touch on the...we finally after many years have two FDA-approved treatments for GA so we will delve into the data from the clinical trials on these agents, and then have some case presentations about which patients might be most appropriate for the use of these new agents and what factors to consider when deciding whether these treatments are appropriate.

 
What are some of the factors that can help clinicians sort through the different case scenarios when one agent may be a better indication than another in certain circumstances? What are some of the guidelines or helpful pearls for them?

 
I think one of the things isn't even which agent, but more so whether any treatment is appropriate for them. And I think the factors such as the fellow eye and what the vision is like there, how close the areas of geographic atrophy are to the fovea, as well as the presence of neovascular AMD, either in the fellow eye or in the eye for which we might be considering treatment are all very important considerations.

 
As you mentioned, it's exciting to have these two new approved therapies in this space. And there's a lot going on in geographic atrophy in general in terms of other advancements, therapies, and approaches. What are you most excited about in terms of geographic atrophy and what this means for patients?

 
I think looking long term, stem cell therapy is one of the more exciting treatments. And there have been some Phase 1 and 2 trial data on this that's not ready for prime time yet, but certainly offers hope for the future to not just slow progression, but potentially to even reverse some damage that's occurred.

EyeCon 2024: New treatments in geographic atrophy from detection to intervention

Emily Chew, MD, won this year's Proctor Award Lecture and gave an outline of the lecture at ARVO 2024

ARVO 2024: Tackling the epidemic of AMD and reintroducing prevention strategies with this year's Proctor Award Lecture winner

With age-related macular degeneration (AMD) cases estimated to double in the next 25 years, Emily Chew, MD, reintroduced the importance of prevention strategies at this year's annual Association for Research in Vision and Ophthalmology (ARVO) meeting. Chew's lecture landed her this year's Proctor Award.

- The following transcript has been lightly edited for clarity.

Hi, I'm Emily Chew. I'm from the National Eye Institute. I was very privileged and honored to have received the Proctor Award this year. I'm going to tell you a few words, and just a few thoughts from this lecture that was given yesterday at ARVO. The talk was entitled "Tackling the epidemic of AMD and reintroducing prevention strategies." So age-related macular degeneration, or AMD, is the leading cause of blindness in the high income countries. And in fact, it really is about a third in all of the global type of blindness. And it's been estimated by 2040, we'll have 288 million people who will be affected by AMD. Although the incidence itself, that's number of people that's getting it each time, is sort of is reduced to some extent, because [we have a] better lifestyle, we're not smoking as much, we're eating better. But the number of people who actually are growing older, is increasing. So by 2050, instead of a billion people that are 60 years old in 2020, we will have 2.1 billion people, so it's doubling. And we're going to have over 436 million people over age 80. So the number of patients will really increase. So in order to really help this epidemic, what can we do? So there's some prevention methods we all know about already AREDS/AREDS2, are supplements, and multivitamins and zinc that we actually tested in National Eye Institute. And AREDS2 was sort of the final supplement because we discovered that beta carotene can increase the risk of lung cancer in former smokers. So for this reason we recommend people who have intermediate AMD should have or should be put on AREDS supplement, especially AREDS2, which has lutein, Zeaxanthin, vitamin C, vitamin E, zinc and copper. That can reduce the number of people from going blind or getting macular degeneration by as much as 300,000 people in five years. In addition to that, we're looking at the 'omics or the metabolomics, and proteomics to learn how we can actually better look after people with early AMD. We believe prevention is very important. If we can do something early, that would be much better than having to have get late disease [treatment]. Late disease treatments are effective for neovascularization. But we're looking for better ways of giving it with less burden. In geographic atrophy, we're starting with some good drugs, but we need better efficacious drugs. So the unmet need is that we really need to look after these patients. It will be a huge number by the time we get older in the next decade or two, even though it's going down, but the number is gonna go really high up.

The last thing I want to talk about is the fact that we can help physicians look after patients by using artificial intelligence. Medical artificial intelligence can help us better diagnose and perhaps detect disease, monitor disease, and even predict disease, and that might help us better care [for] patients. And there's going to be a shortage of physicians. So the more we can help the physicians, the better we will be. So with this, I think it's important to think of prevention for macular degeneration. That's going to be the key. And we at the National Institute are working on projects that do prevention, prevention, prevention.

Well, I was delighted to get the Proctor Lecture Award. It was especially sweet because there's two awards, the Proctor and the Friedenwald Award, and my buddy from National Eye Institute got it. So it was shining a light on the National Eye Institute. So it's really not just for me, it's for our institute. The fact that we all work together and our colleagues get together and our common mission is to reduce blindness and improve the quality of life in patients. So it's very meaningful for us, especially when the two of us have gotten it and it's a real, it's a real honor to to be part of this

Emily Chew, MD, who won this year's Proctor Award, outlines her presentation on preparing for estimated doubling of age-related macular degeneration cases in the next 25 years at ARVO 2024.

Mary Beth Yackey, OD, and Michael Javaheri, MD, share their perspectives on the modernization of geographic atrophy identification and treatment.

CIME 2024: Outlining the new standard in geographic atrophy

On May 4, 2024, eye care professionals gathered at the 18th Annual Controversies in Eye Care meeting in Los Angeles, California. During the meeting, Mary Beth Yackey, OD, Michael Javaheri, MD, and Christopher Riemann, MD, participated in an exciting panel that discussed care optimization and the modern treatment paradigm for patients with geographic atrophy. Here, Yackey and Javaheri share commentary on the panel.

Editor's note: This transcript has been lightly edited for clarity.

Hi, my name is Mary Beth Yackey. I'm an optometrist from the Cincinnati Eye Institute in the vitreoretinal team from Cincinnati, Ohio. Today I'm going to join my esteemed colleagues to bring to you the new discussions on our new standard of care for treating geographic atrophy. It's an exciting time and we're learning more and more about geographic atrophy as the days go by, and the treatments get broader. In 2023, we had exciting new standards of care, obviously, with 2 new drugs introduced. My job today is to bring to you and explain to you what geographic atrophy is and how it affects our patients lives on a daily and what we might be able to do to help them not only in the treatment standards, but also in helping them in their daily lifestyle to help their quality of life. I hope you'll learn from myself and my colleagues about this great topic, and I hope you can take it home to your practice to apply it to your patients in the daily life.

Hello, my name is Michael Javaheri. I'm a practicing retina specialist in Beverly Hills, California. My talk today focuses on multimodal imaging for geographic atrophy. By using multimodal imaging to identify geographic atrophy at its early stages, we can track its changes and also with concurrent treatments help monitor its progression. By doing this, we're able to better provide care for our patients in the long run. By using multimodal imaging, our optometry colleagues can help follow geographic atrophy and know when it happens. By knowing when it happens, they can refer patients for care in a prompt manner.

So for optometrists, we want you to be looking at the patient with new eyes, looking for geographic atrophy. For so many years, we could not do anything for geographic atrophy. Treatment was definitely not on our forefront and we would just tell our patients, you know, go get some low vision aids and come back and see me in a year. Now we want to tighten those followups and offer them the opportunity to have treatment if a retina physician near you is treating, or at least given the opportunity to seek further ideas from a retina specialist.

Our take home message is that using multimodal imaging, fundus photography autofluorescence, and OCT all together is the best way to help early changes with regard to geographic atrophy.

Thank you for having me today, and it's a pleasure to be here.

CIME 2024: Outlining the new standard of care in geographic atrophy

Mohammad Rafieetary, OD, FAAO, FORS, Dipl ABO, ABCMO, met with Optometry Times to discuss his upcoming presentations on OCT, AMD imaging, and the PULSAR clinical trial at the American Academy of Optometry.

This video transcript has been lightly edited for clarity. 


Hi everyone. I'm Emily Kaiser Maharjan with Optometry Times and I'm sitting down with Dr Mohammad Rafieetary, who is presenting a variety of topics on AMD and imaging at the American Academy of Optometry meeting in New Orleans. Welcome, I'm so glad you could join us.

Mohammad Rafieetary, OD, FAAO, FORS, Dipl ABO, ABCMO:


Thank you, me too. Good to see you as always.


Of course. So, can you tell us a little bit about the presentations?

Rafieetary, OD, FAAO, FORS, Dipl ABO, ABCMO:


Sure. So I got 2 lectures and a poster that Academy. One lecture is about practical use of OCT looking at morphology, looking at tomography instead of topography. It is about time for me and my colleague [to] start looking a little bit deeper into biomarkers of various diseases, including age-related macular degeneration, diabetes, looking at OCT a little bit closer because it's technology that actually gives us a lot of information. We often overlook that information, we want to jump to diagnosis without really understanding what's happening at tissue level. So this technology allows us to do that. 

The other lecture is imaging specifically for AMD, all the different multimodal imaging. Up to recently, pretty much OCT or imaging evaluation, or even clinical imaging of patients with AMD was, "do they have fluid or not? Is this with AMD or not?" Now, we have treatment for dry AMD, the advanced form of geographic atrophy, so we have to pay a little bit closer [attention] now. We have to be able to stage these patients better so we can put the ICD-10 code more appropriately so we have [a] better understanding of how many of these patients exist in clinical practice. Then, go through this as that staging progresses to geographic atrophy, when do we refer patients to retinal specialists, particularly when we either have risk or have neovascular AMD to catch them quickly and send them, again, for treatment. So, that's the gist of the second lecture.

 My poster is about [the] PULSAR clinical trial, which was the clinical trial that was [a] multicenter study sponsored by Regeneron. They looked at a little over 1000 patients who had neovascular AMD, and they compared the current standard, or what was current because now it's FDA approved. [It compared] the EYLEA HD, the 2 milligram every 8 weeks, versus the high dose, which has about 4 times more molecular size or efficacy, which is the 8 milligram every 12 to 16 weeks. Part of the problem with dealing with patients with neovascular AMD is [that it is] a chronic disease. So, these patients have to have every four weeks, every six weeks, every eight weeks treatment. That creates a couple of things– there is the burden of treatment and there is injection fatigue. New technology is looking at either change of what we have available, or what can be in the future, where you can extend this injection, so [it] gives more time in between injections to the patients. So, this looked at the 8 milligram in 12 to 16 weeks, and the clinical trials showed that [it] is non-inferior to the 2 milligram every 8 weeks. You can actually extend treatment up to 16 weeks, which is 3 months to 4 months, and maintain not only function but maintain the tissue. They looked at the OCT changes, whether or not the patient were hemorrhaging or not, they had any anatomic change, or they had any vision change where they had to be rescued and be injected sooner than the 12 or 16 months. So, we're looking forward [to] the EYLEA HD FDA approv[al] for neovascular AMD and diabetes. So, hopefully patients get a little release from these monthly or every other month injection.


Yeah, fantastic. So that is a whole lot of retina. How can practice owners leverage this information to better run their clinic?


So for instance, the 8 milligram aflibercept, if this pans out and patients can visit the retina doc less often in the community. OD's can see these patients between those visits and co-manage a little bit better, as opposed to the patient not wanting to come back to the OD's office because now they're going to see retinal specialists every month. There is a flaw to that too because there are other comorbidities these patients have, there [are] other needs that patients have that they may not be able to get at the retina specialists office, so they have a better opportunity to manage and police their patients. As far as the OCT technology, again, [it] allows better diagnoses [to] this patient to send them at the appropriate time, as opposed to over or under [referral of] this patient. So that's the take home message.


Fantastic. What do you think that the future of imaging and AMD will look like?


I think we are just [on] the tip of the iceberg. I mean, imagine imaging is sort of like your cell phones. Every time you get a new cell phone, you think that's gonna be the best ever. Then 6 months later, that cell phone technology, people are gonna show you another better camera or something, you know. As far as treatment, the fact is, these 2 conditions, diabetic retinopathy and age related macular degeneration aren't gonna go away. The patient population of these 2 specific conditions is ever increasing. So, we have to have better ways to manage these patients because we still see patients lose eyesight from this diseases, even with the good technology and treatment we have right now. There has to be a push to do better for these patients.


Is there anything else you want to add that we haven't touched on?


No, just see you all in New Orleans at the Academy. I'm also doing a couple of industry talks for geographic atrophy with some of the other colleagues. [I] hope to see you at all of these events and have a good time in New Orleans.


Fantastic. Well, thank you so much for taking the time to chat today and I can't wait to hear more about your AAOpt presentations.

Optometry Times sat down with Mohammad Rafieetary, OD, FAAO, FORS, Dipl ABO, ABCMO, to discuss his upcoming presentations at AAOpt.

AAOpt 2023: Taking advantage of everything OCT has to offer

At the 2023 American Academy of Optometry (AAOpt) Meeting, Steven Ferrucci, OD, FAAO, and Carolyn Majcher, OD, FAAO, presented a lecture entitled, "Imaging Techniques and Emerging Therapies for Geographic Atrophy." Ferrucci sat down to discuss key takeaways from the lecture.


Hi, everyone. I'm sitting down with Dr. Steven Ferrucci to talk about his presentation on "Imaging Techniques and Emerging Therapies for Geographic Atrophy," which he co-presented with Dr. Carolyn Majcher at the American Academy of Optometry this year in New Orleans. Welcome, Dr. Ferrucci.


Of course. So can you please share with us an overview of your presentation?


As many of you know, there's been 2 new drugs recently FDA approved for the treatment of geographic atrophy. One made by Apellis called Syfovre and another one made by Iveric Bio called Izervay. So we talked about those a little bit in our lecture today.

Really, you know, the the main point that we talked about is now that we have these therapies for geographic atrophy, it's really important as optometrists to be able to recognize patients with geographic atrophy, diagnose patients with geographic atrophy, and then refer those patients who might be good potential treatment patients over to the retinal specialists to at least consider treatment.


Wonderful. So what do you hope clinicians took away from this talk today?


Yeah, I hope that they really learned how to appreciate GA, we talked about multimodal imaging and how you can really find GA in your practice. And, you know, one of the points is that these are patients in the optometric practice, these patients have not been sent over the retinal specialists yet, because there was no treatment. So they're already in our offices. We've been seeing them. And now we have to do a better job recognizing geographic atrophy.

So we talked about multimodal imaging, and how you can find these patients through OCT, color photos, and fundus autofluorescence. Of the 3, OCT is probably the gold standard. And when you do an OCT, you kind of look for hyper transmission defects where the OCT penetrates more in the geographic atrophy area due to loss of the RPE. Color photos are also useful, perhaps not as useful as OCT, but more ubiquitous. So we spoke about that as well.


And kind of building off of that, looking at the patient care side of things. What does this mean for patient care?


Yeah, it's exciting. It's an exciting time, because this is the first time we have anything to offer our patients with geographic atrophy. And another thing we spoke about is that a lot of us think that geographic atrophy is a slowly progressive disease. But the recent natural history studies show us that that's not necessarily the case. And it may progress a little bit quicker than we anticipated. So we discussed that as well. But the real issue is, you know, now that we have this treatment, it's exciting, because now we can do something for patients with geographic atrophy, rather than just sitting by and watching their vision get worse and worse and worse.


Is there anything else you'd like to discuss about what you guys hit on today?


No, just that it really is important, you know, in my mind to start to identify these patients with geographic atrophy, talk to patients with geographic atrophy, see if they're a good candidate for this treatment, and if so refer them over the retinal specialists to at least consider treatment.


Wonderful. Well, Dr. Ferrucci, thank you so much for your time today.

Steven Ferrucci, OD, FAAO, discusses imaging techniques and treatment options for geographic atrophy as part of his AAOpt presentation alongside Carolyn Majcher, OD, FAAO.

Video Series

AAOpt 2023: What optometrists needs to know about geographic atrophy

Arshad M. Khanani, MD, MA, FASRS, talked with Marlisa Miller, editorial intern for 

 to discuss the recent FDA approval of avacincaptad pegol intravitreal solution (Izervay) for the treatment of 

Arshad M. Khanani, MD, MA, FASRS, sat down with Optometry Times to discuss the recent FDA approval of avacincaptad pegol intravitreal solution for treatment of geographic atrophy.

Geographic Atrophy

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