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Spotlight

Presbyopia: A part of Aging and Challenges

Clinical

1rem

Bausch + Lomb and Modulight announce the photodynamic laser for use with photodynamic therapy was approved by the FDA for the treatment of patients with subfoveal choroidal neovascularization due to AMD.

ML6710i photodynamic laser for use with VISUDYNE approved by the FDA

According to the company, the approval allows Eyenuk’s EyeArt AI eye screening system, already approved for detection of diabetic retinopathy, to aid millions of additional patients at risk for vision loss.

Eyenuk gets greenlight to market AI screening system in European Union

Researchers used obesity as a model to accelerate and exaggerate the stressors experienced by the body throughout life.

Obesity linked to macular degeneration

The study advances the understanding of the leading cause of visual impairment in adults.

Combining multiple maps reveal new genetic risk factors for blindness 

The study could lead to early diagnosis and treatment of age-related macular degeneration.

Mount Sinai researchers first to identify that two separate eye diseases may contribute to common blinding eye condition

I’d never seen an idiosyncratic reaction to faricimab like this. In my experience, faricimab tends to dry up persistent fluid a bit better than Eylea. Those are the majority of cases when I use faricimab. In this case, I was initially worried about postoperative inflammation and macular edema being factors, so I tried restarting their topical drops and other agents geared toward drying up the macula. I didn’t see much of an effect. In fact, it appeared to be worse, which convinced me that there was a choroidal neovascular component present, so we proceeded with the anti-VEGF biologic injection.

Unfortunately, the patient still had an inflammatory component. That idiosyncratic-appearing reaction to that faricimab might have been a fluke because of the inflammation. Persisting with the faricimab may have helped the fluid resolve. More likely, adding a steroidal anti-inflammatory, as mentioned by many of our participants, might have been a reasonable option: sub-Tenon Kenalog, an intravitreal dexamethasone implant, or an intravitreal fluocinolone acetonide 0.18 mg implant to treat posterior uveitis. Any of those options would be good in addition to continuing with our anti-VEGF injections to treat the wet AMD [age-related macular degeneration].

Those are the key takeaways. Sometimes you can have overlapping components, including an inflammatory component, on top of the wet AMD because of prior ocular surgery.

® presentation. We hope you found this presentation informative and applicable in your practice.

Videos

Daniel F Kiernan, MD, FACS, discusses idiosyncratic biologic response to anti-VEGF treatment in a patient with neovascular AMD.

Impressions and Takeaway Points From Case #2

In the second case, an 83-year-old man is referred by an optometrist for a retinal exam. He’s complaining of worsening vision and retinal edema in the left eye for 1 month. He has a medical history of hypertension and GERD [gastroesophageal reflux disease] that are controlled in medication, and he has an ocular history of prior cataract surgeries with intraocular lens implantation in both eyes as well as dry AMD [age-related macular degeneration] in both eyes. The patient has Medicare and a secondary insurance plan.

On February 2, 2022, the patient’s vision is 20/50 in the right eye and 21/50 in the left eye, with normal pressure. Pseudophakia was seen on slit lamp exam. Dilated exam shows drusen RPE [retinal pigment epithelium] changes in both eyes with macular edema present in the left eye. In the following slides, you can see some testing. Fundus photos show drusen in both eyes. Below that, the OCT [optical coherence tomography] of the left eye shows intraretinal edema and drusen. Angiography of the left eye shows early hyperfluorescence due to staining of drusen and some perimacular leakage, which is a little more prominent on the right image. This is consistent with choroidal neovascularization.

However, a small amount of disc leakage could be more consistent with postoperative CME [cystoid macular edema] and postsurgical inflammation. Of note, the patient was pseudophakic. It’s not listed, but they had had an intraocular lens exchange 6 months prior to presentation in that left eye. Because of the suspicion that this might be related to postsurgical uveitis or cystoid macular edema, I restarted the patient’s cataract surgery drops—a corticosteroid, a nonsteroidal anti-inflammatory, and a carbonic anhydrase inhibitor for the left eye—with the goal of drying up that macular edema. The plan was to follow up in a few days to do that angiogram, as well as in 2 or 3 weeks for reevaluation.

Two or 3 weeks later, on February 25, 2022, there was still fluid present—a little more on central subfield thickness—and the vision had gotten worse. This changed my mode of thinking from postoperative CME inflammation to wet age-related macular degeneration. I stopped the eye drops and proceeded with an aflibercept injection that day. The patient wanted to have a driver with him, so they came back about a week later, and we proceeded with their first shot. On April 5, 2022, when the patient came back, we saw an improvement of vision: 21/50 in the left eye with reduction of retinal thickness and edema. We proceeded with a second shot of aflibercept and saw them a month later.

Curiously, the vision improved a bit, but there appeared to be more fluid and an increased amount of intraretinal edema on the left eye, so we continued with the third aflibercept. I saw the patient a month later, and vision had then dropped a line, to 20/60. They had persistent edema, specifically intraretinal fluid on OCT. Nevertheless, we persisted with a fourth aflibercept in that eye. Five weeks later, their vision had dropped again to 20/70. The OCT looked worse, with more intraretinal macular edema.

At this point, the plan changed. I was concerned that they might be developing something like tachyphylaxis, or short-term tachyphylaxis. I wanted to prove to myself that the patient is having a biological response to aflibercept. I gave him another shot that day, the fifth 1 in the left eye, and planned to see him back in 1 week to judge if they did have a biological response. A week later, they definitely had a response with decreased edema and stability of vision, but it was still limited. I’d hoped that all the fluid would go away shortly after that shot, but there was still persistent fluid.

Nevertheless, we plan to follow up in 3 weeks. We decided to switch the product from aflibercept to the new faricimab to see if that might help dry up some of the fluid more effectively, as it had in the clinical trials. We saw them on August 17, 2022. Their vision was 20/60 in the left eye. Macular edema had gotten worse since the last exam, and we proceeded with the first faricimab in that eye. Unfortunately, a month later, the patient came back not particularly happy. I saw that their vision had dropped to 20/200 in that eye, and the fluid had dramatically increased since the last exam. Extensive examination should have no evidence of iritis or detritus in the left eye, or any evidence of any other ocular retinitis or vasculitis.

Because of my concern of this drop in vision, I went back to aflibercept. The patient had not had any idiosyncratic effects before with it. I saw them a month later, and they had improved in terms of their vision and fluid. There’s still edema present, and the vision had dropped back down to 20/60, which seemed to be the best vision possible with Eylea. Nevertheless, it was an improvement over the idiosyncratic reaction we saw with the faricimab. We were more happy with that, so we proceeded with an additional aflibercept. I last saw them on November 16, 2022, when their vision was stable at 20/60, and there was persistent but stable intraretinal macular edema seen on the OCT. Our plan was to continue monthly aflibercept in the left eye.

Daniel F Kiernan, MD, FACS, reviews the case of an 83-year-old male patient with neovascular AMD.

Patient Case #2: 83-Year-Old Male With Neovascular AMD

 In this case, the patient had classic symptoms for wet AMD [age-related macular degeneration] and choroidal neovascular membrane, and they were treated in a way many other patients are treated: by starting with preferred generic products, such as aflibercept. Their insurance allowed them to avoid the need for step therapy with a potentially less effective agent and go straight to aflibercept. They responded very well. Unfortunately, because of their health issues and the burden of care from their other health considerations—specifically chemotherapy for their cancer—they missed several appointments.

For patients who are treated, I usually follow an initial 3 loading doses. Then, following the label, maybe I go to every other month. If they have recurrent fluid, I switch back to every month for Eylea. In this case, the patient missed a few appointments and was stable after these tests of proof of stability. I felt comfortable going farther out sooner than I might have otherwise. I went 2 and then 3 months, even within a year of treatment. The on-label indication is to treat patients with 3 initial loading doses and then every month or every other month for the remainder of the first year. Usually, this can be safely extended. Greater than 50% of patients can often be extended to 12 weeks. This patient was extended to 12 weeks within the first year of treatment. This was extended to 6 months after that, not by design but because of other health issues. Six months is what we hear about when we talk about a fourth delivery system: Susvimo, not Eylea. That was definitely something that could have made a turn for the worse, so I don’t recommend that normally. That’s why I had the patient follow up with quarterly dosing every 3 or 4 months. That would be quite effective for this patient.

You don’t want to extend them too far. Something untoward could happen. They could definitely lose vision or have permanent vision loss if they were to have a subretinal hemorrhage, for example. In this case, by the way everything worked out, this patient stayed quite stable at 2, 3, 4, and even 6 months between shots. That’s not how we want to handle this patient, or any patient, because of the risk of something else happening.

As for the takeaways from this discussion: these injections work, and some patients respond better and last longer than others. When you go past a reasonable period of 2 or 3 months, you’re increasing the risk margin a little too much, and you should be cautious. With some of the newer agents that have clinical trial data showing 3- and 4-month time intervals, I feel more comfortable extending the patient. Even then, how long do these drugs last? A half-life is short, so erring on the side of caution is better. We see that in long-term studies, if patients receive more shots, they tend to have vision preserved for longer, and that erring on the side of more treatment is better than less treatment.

Daniel F Kiernan, MD, FACS, discusses impressions and key takeaways from a neovascular AMD patient case, focusing on treatment intervals.

Impressions and Takeaway Points From Case #1

Hello, I’m Dr Daniel Kiernan, a retina specialist at the Eye Associates in Sarasota and Venice, Florida. I’m excited to share 2 neovascular AMD [age-related macular degeneration] cases that we discussed at a recent 

This is a 79-year-old woman who was referred by an outside optometrist for a retina exam complaining of blurred vision in the left eye for the last several months. Her medical history was typical for an older individual, including hypertension, some heart disease, high cholesterol, and osteoporosis, which are all controlled with medication. She also has lung and breast cancer, and she’s undergoing active chemotherapy on a regular basis. Her ocular history is significant for status postcataract to track the lens in both eyes, and she has a prior history of dry AMD in both eyes. She has Medicare with a secondary plan for her insurance.

On the second slide, you can see that on May 12, 2021, her vision in the right eye is 20/30 and in the left eye is 20/50 with normal interocular pressure. She’s pseudophakic post-YAG [posterior capsulotomy] bilaterally. Her dilated fundus exam shows drusen RPE [retinal pigment epithelium] changes bilaterally, which can be seen on the black-and-white and color fundus [autofluorescence] photos. Below that, on the OCT [optical coherence tomography], we see the presence of intra and subretinal fluid as well as some exudates that are all characteristic and quite diagnostic for wet AMD, which she was diagnosed with that day. Further angiographic testing showed a clear, very classic CNV [choroidal neovascularization] leaking lesion just above the center of the fovea in the left eye, which is consistent with wet AMD. Therefore, she was treated with an aflibercept injection that day in the left eye.

On the next slide, on May 20, 2021, a 1-week safety check was performed. Visual acuity was seen to be 20/50 in the left eye with normal pressures, and you can see near resolution of the subretinal intraretinal fluid on the OCT. All was well, so the plan was to follow up in 3 weeks for the second aflibercept. On June 10, 2022, her vision had improved to 20/40 in the left eye, so a second shot of aflibercept was given in that eye. On the OCT below, you can see complete resolution of all edema originally seen on that central subfield thickness cut.

On July 8, 2022, her vision was 20/40 in the left eye, and the OCT was still quite stable. There’s some scattered appearance to the ellipsoid zone. There’s no clear edema presence, so a third aflibercept was preceded with that day in the left eye. Because the patient was stable after 3 injections, the plan was to follow up in 7 to 8 weeks with a fourth aflibercept, also in the left eye. The patient unfortunately had to reschedule the originally planned next injection. When they came back on September 23, 2021, it had been 10 weeks since their last injection. Fortunately, vision was stable 20/40, and you can see on the OCT that there’s still no new fluid or recurrent edema present. The fourth aflibercept was given with the plan to follow up in about 12 weeks for a fifth aflibercept.

Daniel F Kiernan, MD, FACS, provides an overview of a patient case of a 79-year-old female with neovascular AMD.

Patient Case #1: 79-Year-Old Female With Neovascular Age-Related Macular Degeneration (AMD)

 This transcript has been lightly edited for clarity.

Hi, my name is Scott Walter. I'm a retina specialist in Hartford, Connecticut. And I wanted to talk today a little bit about the year 2 data from the TENAYA and LUCERNE trials.

So TENAYA and LUCERNE were the phase 2 pivotal clinical trials leading to the FDA approval of faricimab for the treatment of patients with neovascular AMD. And in year 1 of the trial, we know that patients got 4 monthly loading doses of faricimab and then patients went into extended treatment arms of 8-, 12-, or 16-week fixed dosing intervals. And that was based on disease activity assessments that took place at week 20 and 24.

In year 2 things changed a little bit in terms of the protocol. So beginning at week 60, patients were eligible to extend or shorten their treatment intervals based on disease activity assessments occurring at each study visit. So this became more of a treat-and-extend type protocol, patients could go ahead by 4 weeks or back by 4 to 8 weeks depending on those disease activity assessments. So I think what happens in year 2 is very interesting to us as retina specialist because it kind of—it reflects maybe how we practice in the real world with a treat-and-extend practice pattern.

So in year 2, 60% of patients were able to extend their dosing interval by 4 more weeks, and the vast majority of patients maintain those dosing intervals through the end of year 2 at 112 weeks.

Ultimately, the number of patients who are maintained at Q-60 week dosing intervals increased from 45% at the end of year 1 to 63% at the end of year 2. So it's really impressive how, you know, the the numbers just keep going up in terms of the proportion of our patients who can be maintained at these extended dosing intervals, about 4 out of 5 patients can be treated in a Q-12 to 16 week dosing intervals, throughout 2 years of treatment with faricimab.

So I think this new therapy really has tremendous promise, the best corrected visual acuity gains and central subfield thickness reductions that were observed in year 1 were maintained in year 2, there were no significant safety signals, low rate of intraocular inflammation and really, absolutely no cases of inclusive or non-inclusive retinal vasculitis identified in the second year of the trial.

So I think this gives us a lot of confidence as retina specialists, as we begin transitioning some of our patients from other anti-VEGF therapies to this new molecule, which is both an anti-VEGF agent and a dual pathway inhibitor that also blocks Ang-2 that we can really achieve extended durability in the vast majority of our patients.

Scott Walter, MD, an investigator in the TENAYA and LUCERNE trials discusses the year 2 data for the treat-and-extend regimen of faricimab for the treatment of nAMD and DME.

Promising results for faricimab revealed in TENAYA, LUCERNE year 2 data

This transcript has been lightly edited for clarity.

 We're joined today with Dr. Justis Ehlers, who is presenting this year at the American Academy of Ophthalmology. Welcome. Dr. Ehlers, could you tell us a little bit more about your talk this year?

 Sure, Sheryl. Thank you so much for having me; it's a pleasure to be able to share a little bit about the data that we're presenting at the Academy meeting.

The focus of the talk, and as some of the research that we're presenting is really around the importance of understanding what's going on from a fluid dynamics standpoint in wet macular degeneration, and how that may impact visual outcomes. There's been a lot of research that suggests that the presence of different fluids may have different impacts on overall visual acuity. In particular, some of the early data has said that subretinal fluid may be associated with better visual acuity and intraretinal fluid may be associated with more significant visual acuity loss.

Interestingly, in some of these studies, they've actually demonstrated that the presence of subretinal fluid may actually be better than not having any fluid in terms of vision. And we wanted to dive into that a little bit more in terms of evaluating ways to look at the OCT, that may have a better understanding for us as clinicians.

And what we were able to do is, using some advanced image processing, is look at the overall intact aspect of the ellipsoid zone and the integrity that's there. And really judging whether or not there may be underlying atrophy.

And what we found was interesting, and that was was that if the outer retina was intact, the retina being dry was clearly the best visual acuity outcome, really suggesting that that really is what we should push for, as clinicians. Subretinal fluid being present was the second in terms of overall visual acuity outcomes, and then intraretinal fluid, and then actually underlying atrophy being the overall worst visual acuity outcomes.

And so you can see how understanding that key feature of the outer retina really drives the difference that may push outcomes towards more limited visual acuity when you sum the entire population together.

The last piece that we looked at was this concept around volatility. And that is, is that if the fluid is changing significantly, does that have an impact overall? And one of the things that we did find that I think was sort of unexpected, was that dynamic subretinal fluid, so that is that fluid that's changing from visit to visit, appears to have a more deleterious effect on visual acuity than fluid that's static.

And so again, really understanding and as we have more and more therapeutics available to us to understand what's happening on a really monthly, and really weekly basis, for these patients will be helpful to understand how we can optimize their outcomes overall.

 Excellent. And what would be the take-home message for the clinician in their daily practice?

 I think you'll one of the key take-home messages is just use caution in terms of how quickly you extend patients, and really understanding early on--is fluid resolving? And you're not just capturing that. And I think you know, striving for the best fluid outcome early on in treatment, in terms of resolution are really the things that I've taken away from this.

 Well, thank you so much for sharing that. We look forward to learning more about your presentation.

At the 2022 American Academy of Ophthalmology meeting, Justis Ehlers, MD, presented a talk titled, "Defining the Fluid Problem in Neovascular AMD: To Dry or Not to Dry?"

NOINDEX

NOFOLLOW

Discussing how fluid dynamic affect visual acuity in wet macular degeneration

At ARVO 2022, Carlos Quezada Ruiz, MD, senior medical director at Genentech, presented his talk entitled, “Predicting optimal treatment regimen for patients with neovascular age-related macular degeneration using machine learning.”

This year at ARVO, we are presenting our data on a pilot study looking at machine learning and its ability to predict treatment regimen for patients with neovascular AMD. We believe that personalized health care and personalized treatment for patients with neovascular MD is the way that we are going to be treating patients and the retina in the future.

And at Genentech Roche, we are committed to better understanding how machine learning fits into this picture and how it can help us evolve into getting to that personalized approach for patient treatment and patient counseling as well, which is so important.

In this work, we evaluated 324 patients who were enrolled in the AVENUE and the STAIRWAY trial, and who received ranibizumab or faricimab for the treatment of neovascular AMD. We evaluated the baseline characteristics of those 324 patients, which included age, sex baseline BCVA, CSD treatment regimen arm. We also included image-derived characteristics from the spectral domain OCTs of all of those patients. We then implemented different machine learning algorithms. In the results, we actually realize that one of them, XG boost, was the one who came with the with the highest R square. This is basically the highest prediction rate for treatment interval for these patients.

Now, what this means for patients is basically that if this algorithm is able to work, in the future we may be able to predict at baseline during that initial visit how a patient might respond over time with regards to BCVA response, but also what would be the most appropriate treatment regimen, meaning the least frequent regimen that would give the best BCVA outcomes for that individual patient.

And while we recognize this is a pilot study of only a small proportion of patients, we do think that we need bigger datasets and more diverse datasets as well to better replicate these results and be able to extrapolate it to a broader population as well.

Carlos Quezada Ruiz, MD, senior medical director at Genentech, discusses “Predicting optimal treatment regimen for patients with neovascular age-related macular degeneration using machine learning.”

Machine learning may predict optimal treatment regimen for patients with nAMD

Dr. Jeff Cleland, CEO of Ashvattha, duscusses safety data for an at-home subcutaneous injection option being developed for wet MD, and DME presented during the 2022 ARVO annual meeting, held in Denver, Colorado.

®. I'm joined today by Dr. Jeff Cleland, CEO of Ashvattha, who will discuss safety data for an at-home subcutaneous injection option being developed for wet AMD and DME. The anti-VEGF candidate will enter a Phase 2 study later this year. Thanks for joining us, tell us about this project.

Thank you, David, I really appreciate the opportunity to join you today. The thesis behind this project came about by the fact that right now everyone has to get an injection with a needle in the eye that gets treated for many of these retinal diseases. And often that occurs every 6 to 8 weeks. And so it's really a heavy treatment burden, not just on the patients, [but ] many of the physicians that we've talked to are really facing a challenge today, being able to actually treat enough patients because of the heavy treatment burden of having to do this administration. 

We’ve looked at it, even from the early days, and when I worked at Genentech, is there a way we can deliver the drug systemically, and really have the same effect as an injection in the eye without the safety side effects? And so that's been our goal and our challenge with our product.

What we are able to show at this year's ARVO is that we are able to dose very safely a very potent anti-angiogenic agent to patients using a subcutaneous administration. And this allows us then to have at-home use of the product by the patients so they can self-administer. Eventually, we will get to market with an auto injector similar to what they do already with an insulin device or something like that. 

And so it makes it much easier on the patient, also easier on the physician. They still have to routinely go back and obviously be checked by the retina ophthalmologist, but at the same time, they wouldn't have to come back in for regular injections into the eye. 

We think this is going to be a real alleviation of the treatment burden for patients and providers. Many patients over time do get burned out and stop coming back for treatment. So maybe we can save a few patients vision over the long term, as well.

Ultimately, what can this mean for patients?

I think the great advantage of this is that the patients that maybe don't even want to consider a needle in the eye will now have an option that's better, and provides them a chance to continue to maintain their vision and make it easy for them to self-administer at home. 

Eventually, and we're working on this now in the background, as well, a possible oral dosage form of the same product. We can offer patients a pill at some point in the future, instead of having an injection in the eye.

You alluded to it, but what's the next step for this study?

So the next step is that we're about to start enrolling patients and a Phase 2 program. These are wet age related macular degeneration patients and diabetic macular edema patients. They've already been treated with an anti-VEGF previously, and they've shown a response to that, but they have to keep coming back in for those intravitreal injections. And so instead of having their next intravitreal injection, they would come back in and get an injection of Eylea or aflibercept. We'd see how long they respond to that injection. So we have a control baseline. And once they have a return of subretinal fluid back to baseline, they'll get a subcutaneous dose of our drug, and we'll again follow them and see how long they respond and how well they respond to our drugs. 

Each patient becomes their own control in the first part of the study. We think this will be a very powerful study to show that the drug actually does have the potential for therapeutic benefit in these patients.

Thank you so much for taking a little time to catch up again with us and I appreciate it.

Jeff Cleland, PhD, CEO of Ashvattha, discusses safety data for an at-home subcutaneous injection option being developed for wet AMD and DME. The anti-VEGF candidate will enter a Phase 2 study later this year.

Therapeutics 

Safety data for at-home subcutaneous injection option for treatment of wet AMD, DME

"We're seeing promising signals that really need to be explored in a randomized fashion so that we can generate data with confidence and hopefully deliver this to patients in the future." Allen Ho, MD, FACS

I'm Allen Ho, and I am a retina surgeon at Wills Eye Hospital, Mid Atlantic Retina and the director of retina research.

So the OpRegen trial is a cell therapy trial, looking to explore potential safety and efficacy for patients with advanced dry age-related macular degeneration (AMD).

If you think about this group of patients — which are growing as baby boomers are enlarging — this is a study to attempt to address the dry form, we currently have treatments for the wet form, including injections, and we're developing treatments for the dry form. This is an attempt with cell therapy to see if we can slow down, stop, or even potentially reverse, vision loss in this group of patients.

There is a great unmet need for patients with advanced dry macular degeneration. In other words, there's no specific treatment for geographic atrophy. We have some programs now — and it's kind of exciting — that are thinking about slowing down the progression of aging, or atrophy, in patients with this condition.... [and] they involve injections.

This is a study looking at a different approach using cell therapy. And in this phase 1/2, non-randomized study, we're seeing a good safety profile with this stem cell line surgically placed under the retina. And most of the patients who had any issues that were reported on safety, were with respect to, for example, the surgical procedure itself with some redness of the eye.

We did see some epiretinal membrane formation, three of which was significant and required surgery in the study. And this is three out of 24 only.

To reiterate, the safety profile of the OpRegen program is very well-tolerated. I want to also add that when you put cells in an eye — [and] these are human allogeneic cells — you have to watch carefully for inflammation, either acute or delayed, or rejection of the cell line. We saw none of that, so the cells are very well-tolerated.

With respect to the different cohorts in observations there, it kind of makes sense that if you try and solve a problem... for example, when the house is not totally burned down, like the initial cohorts that were legally blind with larger areas of atrophy, we saw good safety there and some signals of activity of the cells. But when we looked at cohort four, which was 12 out of the 24 subjects, again, good safety, but also some very promising signs of activity that need to be explored in a larger randomized program.

Specifically, we saw about a seven letter improvement — 7.6 letter improvement — in cohort. Four of those patients with smaller areas of atrophy, and better vision ... about 21/25 starting vision. And we saw interesting structural changes on the OCT, overlying what we presume was the cell deposition in areas of atrophy and some improvement in the retinal architecture where we had transplanted the cell line.

So we're seeing some promising results that need to be explored more, both with respect to anatomy and activity, and even vision with the caveat that this is an open label study. We need to understand these results in the context of a randomized trial. I think we're beginning to understand and refine who the right patient group is. Again, if you think about the goal of trying to slow, or stop, or even reverse aging in any part of your body is a lofty goal but we're seeing promising signals that really need to be explored in a randomized fashion so that we can generate data with confidence and hopefully deliver this to patients in the future.

The OpRegen trial is a cell therapy trial, looking to explore potential safety and efficacy for patients with advanced dry age-related macular degeneration (AMD).

Cell therapy trial shows promising results for patients with advanced dry AMD

Mary Durbin, PhD, Chief Scientific Officer at Heru, discusses the benefits and capabilities of the various testing modalities available in 1 wearable platform with Sheryl Stevenson, 

Mary Durbin, PhD, Chief Scientific Officer at Heru, discusses the benefits and capabilities of the various testing modalities available in 1 wearable platform.

What the re:Vive 2.0 platform may mean for the future of vision diagnostics

What is the largest unmet need that you see on a day-to-day basis? I’ll make it a 2-pronged question. The biggest unmet need, and then how do you think that need is going to be filled over the years to come as our field continues to evolve? Mark, I’ll start with you.

: All these treatments are exciting on the horizon, I think we’re hitting that unmet need, which is trying to increase the efficiency of our treatment, to decrease the burden of the treatment but also increase the efficacy at the same time. COVID-19, looping back a little, has showed us that patients are scared to come in, but they’re also scared to lose their vision. It’s not only going to be a huge success for treating our patients during this pandemic, but even beyond that, and the future is bright for a lot of these new treatments that will transform the way we give them.

: I agree, treatment burden, obviously. In efficacy, we have reached very high efficacy, but then we have to think, what limits vision? It’s atrophy and fibrosis. And yes, those are other things that need to be worked on with regenerative therapies. There’s a lot of potential there as well.

: I’ll unpack that for a second. You bring up the gorilla in the room in many ways, which is this concept of atrophy. We have the final common pathway for many of these eyes, which is where they become atrophic, whether you call it GA [geographic atrophy] or MA [macular atrophy], now we’ve got cRORA [complete retinal pigment epithelium and outer retinal atrophy]. We’ve got all these terms for this issue where the retina basically becomes atrophic. There is a lot of activity there, too much research to unpack in this short period. But it is exciting. We’re going to have phase 3 data from an inhibitor of C3 cleavage coming out in the second half of this year. And let’s say theoretically, that does become approved, and we have a molecule now that’s on label to slow geographic atrophy progression. How do you see incorporating that into your practice? Diana, I’ll refer that to you.

: It would be great to actually preserve vision before it’s lost. Of course, a lot of these clinical trials involve patients who already have center-involved geographic atrophy, so there’s really no chance of improving their vision. We’re just trying to limit the growth of the atrophy. You almost want to try the agent in people who have geographic atrophy that has not moved to the center, that might be juxtafoveal or extrafoveal, to try to preserve their central vision. I would be inclined to perhaps try it in that subset of patients who can benefit from stopping atrophy.

: Very insightful. Mark, what’s your thought on how these inhibitors of GA progression will unfold clinically?

: Diana brings up a good point, the exact location of the atrophy. And as Sophie was saying, it’s trying to understand the atrophy process itself in terms of increasing our efficacy for treating these patients with wet AMD [age-related macular degeneration]. I do think there will have to be something in the pipeline later on that address’s other parts downstream or upstream that are leading to these unfavorable aspects of the disease in these patients. As soon as we can target those in addition to VEGF, we’ll be going in the right direction, and giving the most preservation of vision for these patients. If we continue to keep our eye on the prize in the research realm, we’ll be headed in the right direction.

: Super comments. Diana, I’ll bring it back to you then. The largest unmet need and how we’re going to fill that need over time.

: For me, the unmet need in most of my patients is durability of action. We’re seeing with a lot of these new agents in clinical trial development, that companies are trying to address that. When we look at real-world data, we see that a lot of patients in clinical practice receive on average 5 injections of VEGF inhibitors over a 1-year period. That’s why we’re not seeing the terrific visual acuity outcomes we would expect in patients who participate in clinical trials. If we can develop new agents that need to be injected 5 or fewer times a year in the office, that would be a game changer.

: Thanks again to all of you, and thanks to our viewing audience. We hope you found this 

 discussion to be useful and informative. Thank you.

Expert panelists provide an overview of current unmet needs in wet AMD care and discuss the potential for improving clinical outcomes and treatment burden.

Unmet Needs and the Future of Wet AMD Care

: Diana brought this up, but let’s come back and talk directly again about faricimab. I’m curious about everyone’s perspectives here. This is the latest and greatest phase 3 data we have to digest; it just came out publicly a couple weeks ago. It blocks angiopoietin-2 in addition to VEGF-A. We have the neovascular AMD [age-related macular degeneration] data as well as the DME [diabetic macular edema] data. It’s unusual to have 4 phase 3 trials to digest at once, 2 in wet AMD and 2 in DME. We heard Diana’s perspective. I completely agree with that. Sophie, what was your takeaway from the faricimab data that were presented?

: Certainly in AMD, faricimab [Genentech] was compared to Q8 [every 8 weeks] aflibercept. And yes, about half of the patients on faricimab could go out to Q16 [every 16] weeks. I just know that from our clinical practice, that does not occur. Even though in the trial, technically, they didn’t compare 16-week aflibercept to 16-week faricimab, most of us who have treated a lot of patients are very hopeful when we see those numbers and that extension. It holds great promise. I’m looking forward to its approval.

: Yes, exciting. Let’s talk about the other non–VEGF-A targets from the other molecules. You have OPT-302, briefly, which is targeting inhibition of VEGF-C, and D, in addition to VEGF-A, with concurrently administered either ranibizumab or aflibercept. There was a large phase 2 trial that suggested superior vision outcomes. That’s moving forward in a pair of phase 3 trials, a global phase 3 program is initiating enrollment supposedly soon. Any hope, Mark, that blocking additional VEGF family members is going to add value in this disease phase?

: We see it now with the agents that we have, the more different VEGF molecules we get, potentially the more robust the response. And as you pointed out with the trial data so far, it hasn’t been disappointing. It’s helpful. There have been some preclinical data with some other molecules as well, showing that ultimately VEGF is a beneficial target for us. But at the same time, we do have the capability of looking at other ways to target the neovascular disease. The more molecules we can target, certainly the better, and maybe even new pathways as well. For example, there’s the Runt-related transcription factor 1, it came out in 

, and it seemed like a robust target potentially for another agent down the line as well. It’s exciting to see everything that’s coming out.

: Charlie, it’s always interesting when you’re employing combination therapy because the OPT-302 requires a separate injection from the anti-VEGF agent. It’ll be interesting to see if it does show some added benefit such that patients would want 2 injections in 1 visit.

: Yes, great comment. Diana, take us even further downstream. Now we have all of these TKIs, these tyrosine kinase inhibitors, in the space. The theory here is to block intracellular signaling from all of the VEGF family members. You get the effect of OPT-302 plus Eylea or plus Lucentis, or whatever other medication blocking VEGF you’re going to use. Do you think these TKIs have a role in our space? We’ve talked about them for years.

: Yes, I know TKIs, tyrosine kinase inhibitors, are being evaluated by several companies. axitinib is being evaluated by Clearside [Biomedical] as a suprachoroidal injection that could have beneficial effects and long duration of action. In addition, Graybug [Vision, Inc] is evaluating sunitinib as a long duration, every 6 month-administered intravitreal injection. And of course, EyePoint [Pharmaceuticals, Inc] is evaluating their drug as well looking at a sustained delivery of a TKI inhibitor. All these in theory have the potential of working and will be put to the test when they go against our current anti-VEGF therapies.

: It’s exciting. There is a tremendous amount of activity in trying to achieve better and more sustainable outcomes for our patients.

Key opinion leaders in ophthalmology comment on the potential role of alternative targets beyond VEGF-A including VEGF-C/VEGF-D and tyrosine kinase inhibitors. 