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Ophthalmology Times Europe – Clinical Insights for Eye Specialists

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Heidelberg Engineering: Enhancing the Patient Journey

Clinical

1rem

An understanding of GA growth kinetics is key to addressing the pathophysiology of age-related macular degeneration

Progression rates vary in subtypes of geographic atrophy lesions

AMD treatment may become unrecognisable as gene therapies evolve

Starting from scratch on neovascular age-related macular degeneration

New financing will support the company's lead retinitis pigmentosa programme, among other projects

Australian biotech firm Mirugen secures major funding for cell reprogramming therapy

According to the company, the EMA’s opinion was based on the “totality of evidence comprising a comprehensive analytical, non-clinical and clinical data package”

Alteogen receives positive CHMP opinion for aflibercept biosimilar EYLUXVI

Health Canada approves Aflivu, a biosimilar for retinal diseases, enhancing treatment options and affordability for Canadian patients.

Health Canada approves aflibercept biosimilar Aflivu

Omer Trivizki, MD, MBA, a retina specialist from Tel Aviv Medical Center, speaks about VOY-101, a Novel, Complement-Modulating Gene Therapy for Geographic Atrophy

Clinicians and industry partners continue the race to find the most efficacious therapy for 

. A new gene therapy may solve the puzzle for patients with non-neovascular AMD, and more information is coming soon from a Phase 2 trial, according to one retina researcher. Omer Trivizki, MD, MBA, a retina specialist from Tel Aviv Medical Center in Israel, shared details about VOY-101, a novel, 

complement-modulating gene therapy for geographic atrophy (GA).

The Eye Care Network caught up with Dr Trivizki at the 

American Society of Retina Specialists (ASRS)

 Annual Meeting in Long Beach, California. He explained the mechanisms beyind VOY-101( Perceive Biotherapeutics, Inc.) and the Phase 1 Beyond study (NCT06087458). 

"In our talk, we showed that VOY-101 is safe and tolerable," Dr Trivizki recounted. A 12-month survey of 24 enrolled patients showed there was no dose limiting toxicity, no systemic adverse effects and no ocular adverse effects, he said. "There was a really mild, transient intraocular cell effect that we observed during the study, which passed with topical steroids only, and eventually all patients were off steroids with no recurrence," Dr Trivizki said. "That led us to the conclusion that we can move ahead to the Phase 2 [trial] which...[dosed the first patient in late June]."

Dr Trivizki went on to explain the mechanism of the treatment, which is designed to provide patients with Complement Factor H gene (CFH) protection. "CFH protection is a protein that was found to 

," Dr Trivizki said. "The idea here is to provide, with one intravitreal injection, the protection effect of CFH...[and] to be able to use the eye as a production for this specific protein, so with a single injection, you can treat the patient for the long term."

Dr Trivizki explained that the Phase 1 trial had six sites across three countries, with most of the patients in Tel Aviv. The follow-up, Phase 2 trial, Journey, has started enrollment and dosing, and will follow patients to a 12-month primary endpoint, he added.

Videos

A 12-month follow-up indicated no dose limiting toxicity and no ocular or systemic adverse effects

First clinical results demonstrate efficacy of VOY-101, a novel gene therapy for GA

SriniVas R. Sadda, MD, FARVO, shares key points from his retina presentation at the International SPECTRALIS Symposium

At the International SPECTRALIS Symposium – and Beyond (ISS) in Heidelberg, Germany, a lineup of imaging experts shared their thoughts on the ever-changing field. SriniVas R. Sadda, MD, FARVO, presented a lecture on high-resolution optical coherence tomography (OCT). At the ISS, he said high-resolution OCT shows diagnostic and prognostic promise for atrophic and precursor lesions in age-related macular degeneration (AMD).

Biomarker-based risk stratification is a strategy Dr Sadda already uses in his clinical practice, he said. “We’ve spent a lot of years trying to establish the pathway to the development of atrophy in AMD,” he said. "These biomarkers are very important to recognise."

High-resolution OCT has a stronger axial resolution than standard-resolution OCT, giving structural features of the eye a distinct appearance. This allows clinicians to distinguish true hyperreflective foci from retinal vasculature, for example. Additionally, clinicians can differentiate incomplete retinal pigment epithelial (RPE) and outer retinal atrophy (iRORA) from complete RPE and outer retinal atrophy (cRORA), a vital distinction to make in treating patients with AMD.

Watch the full video to hear how the nuanced monitoring made possible by high-resolution OCT can help diagnose and treat patients.

High-resolution optical coherence tomography illuminates crucial biomarkers in age-related macular degeneration, Dr Sadda said

Anat Loewenstein, MD, describes her presentation on remote imaging for age-related macular degeneration and geographic atrophy at the International SPECTRALIS Symposium, in conversation with Hattie Hayes of Ophthalmology Times Europe

Anat Loewenstein, MD, co-chaired the retina session and presented in the distributed care session at this year’s International SPECTRALIS Symposium (ISS). She is the director of the division of ophthalmology at Tel Aviv Medical Center in Israel.

Prof Loewenstein commented on trends in the contemporary imaging landscape, a key segment of her ISS presentation on home monitoring. “Something that comes up loud and clear is we need to find ways to correlate between function and morphology,” Prof Loewenstein said. “Everyone looks for imaging that will show biomarkers that are predictive of progression.”

Prof Loewenstein said that, along with optical coherence tomography (OCT), advanced technologies like OCT angiography (OCT-A) and fluorescence lifetime imaging ophthalmoscopy (FLIO) are quickly changing what is possible in diagnostics. That's good news for patients with age-related macular degeneration, geographic atrophy and other retinal pathologies. However, she warned that technology alone is not enough to improve and preserve patients’ health outcomes.

“You cannot use remote monitoring as a standalone [tool.] Everyone wants to use AI and remote monitoring, but you need to coordinate with your health system,” she advised. “[Remote monitoring] needs to be supported by the community of retina physicians and of ophthalmologists, so the healthcare system and the payers will be in agreement with the need to use it in our system.”

Watch the video to hear Prof Loewenstein’s full interview and learn about her presentation at the ISS in Heidelberg, Germany.

Anat Loewenstein, MD, presented real-world results of remote imaging at the International SPECTRALIS Symposium


Modern monitoring strategies remove major barriers to retina care

Impact of Durable Therapies on Patients and Clinics and Monitoring Strategies

Video content above is prompted by the following:

As treatments with greater durability emerge, how might they change your approach to treating neovascular age-related macular degeneration or diabetic macular edema? What impact will this have on treatment and monitoring schedules?

How will this impact workflows and clinic capacity?

Panelists discuss how longer-acting treatments will enable extended intervals between visits while requiring careful adjustment of monitoring protocols and clinic workflows to balance reduced treatment burden with maintaining adequate disease surveillance.

Video Series

Angiogenesis 2025: The global forecast for AI-driven home OCT, featuring Anat Loewenstein, MD

Angiogenesis 2025: The global forecast for AI-driven home OCT

Following the 22nd Annual Angiogenesis, Exudation, and Degeneration Meeting, held virtually on February 8, 2025, Anat Loewenstein, MD, shared key takeaways from her presentation. Prof Loewenstein is Professor and Head of Retina, Division of Ophthalmology at Tel Aviv Medical Center, Sydney Fox Chair of Ophthalmology at Tel Aviv University, and President of the Israeli Ophthalmological Society, all in Tel Aviv, Israel. She also serves as the President of the European Society of Retina Specialists (EURETINA).

Prof Loewenstein presenting findings from a cross-sectional pivotal home optical coherence tomography (OCT) trial that compared the performance of artificial intelligence (AI)-enabled algorithms with human expert graders in neovascular age-related macular degeneration (nAMD).Overall, the study demonstrated that combining home OCT with AI provides a high level of precision and repeatability, enhancing patient care and disease monitoring for AMD. Here, Prof Loewenstein shares her findings and discusses the broader implications for home OCT in the years to come.

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

: So we are joined today by Professor Anat Loewenstein. Welcome to you, always a pleasure to see you. We would just love to hear a little bit of a summary of your talk at this year's Angiogenesis meeting. You spoke about a home OCT trial.

: Thank you very much, Sheryl, it's always a pleasure to talk with you. The Angiogenesis Virtual Meeting was an amazing meeting. I think it practically discussed everything that is relevant in the field of retinal disease from well known experts and I learned a lot.

For my talk, the topic was the pivotal home OCT trial to compare the performance of AI-enabled algorithms with human graders in neovascular macular degeneration. And this is actually one of the two pivotal trials that led to FDA clearance of the [Notal Vision Home OCT device SCANLY]. The presentation described how to clear AI algorithms for OCT systems and discussed the implication of its performance on the clinical management.

We've already shown that home OCT and in-office OCT are comparable in identifying hyperreflective spaces. And also, we've already shown the patients are able to acquire the images on a regular basis. The challenge still is how to manage this large volume of data which is created by the home OCT. And the goal of this presentation was to study the performance of AI with the Home OCT and to understand its impact on the management of our patients.

So for the study, patients acquired four scans on two home OCT devices. All scans were processed with the AI-based algorithm for the hyperreflective areas, segmentation and also volume estimation. In the 10% of the B scans of home OCT were annotated by three expert graders. In addition, the patients acquired one scan on an in-office OCT, and that was again annotated by three expert graders. And all the patients had neovascular macular degeneration.

We looked at two outcomes: One, repeatability, which is a measure of precision, saying looking at the similarity of...estimate for the same eye with multiple scans and grading experts, and at agreement, which is the similarity in segmentation by AI and graders, which is measured by the Dice similarity score.

When we look at the results, when we look at the repeatability, the results are very good. The coefficient of variation was 11.1% on the home OCT and 16% for the in-office OCT. This is when you examine eyes that have a pretty large amount of fluid of at least 10 volume units. So the results show good precision for both device grader combinations on home OCT and AI. It's more repeatable than in-office OCT and the grader. We also looked at agreement. And here we showed excellent agreement in terms of volume estimation with an AI grader Dice score on par with those in between two human graders. So the comparison is very similar. So you know, we do think that combining the home OCT with AI gives physicians insights that have never been before into the disease dynamic, showing the estimation the AI estimation of the hyperreflective spaces, or projection map, and longitudinal, total retinal hyperreflective spaces, volume trajectory, and the ability to set the thresholds to get notification.

So for now, it's going to be commercialised only in the United States, because of the size. To operate the home OCT, you need a monitoring centre. It's not a device that you go and buy in the supermarket, that you can go and give everyone. You need, a monitoring centre that actually supplies the device and monitors the compliance, and the fact that there is an alert, and the fact that patient is, attentive to the alert. And for now, itwill be applicable in the United States, after establishing the reimbursement levels, and then other big countries.

Everyone is looking at biomarkers. Home OCT is very good at detecting fluid, very small levels of fluid. But there are many other things that it's not it's not proficient at detecting. So I think it's mainly [used for detecting fluids]. And of course, it's also important in diabetes and other diseases, but not as [much as] it is important in macular degeneration, where time is of the essence.

Professor Anat Loewenstein, MD, speaks about her presentation from the 22nd Annual Angiogenesis, Exudation, and Degeneration Meeting

Strategies for Loading Dose Sse for Treatment-Naive and Switch Patients

How strictly do you adhere to the loading dose recommendations for new therapies in treatment-naive patients with neovascular age-related macular degeneration and diabetic macular edema?

How about for patients who are switching therapies?

Panelists discuss how loading doses remain crucial for treatment-naive patients to achieve rapid disease control, while patients switching therapies may require modified approaches based on their prior treatment response and disease activity.

Perspectives on the Usefulness of Real-world Data

How do real-world data contribute to understanding the effectiveness of a therapy? What challenges arise when translating clinical trial results into real-world practice?

Panelists discuss how real-world evidence provides crucial insights into treatment effectiveness across diverse patient populations and clinical settings while highlighting challenges in maintaining clinical trial protocols’ stringent adherence and monitoring in everyday practice.

Safety Profile of New Therapies

Based on the clinical trial data, how do you view the safety profiles of faricimab and aflibercept 8 mg?

Does the long-term safety profile of aflibercept 2 mg increase your confidence in the safety of aflibercept 8 mg?

Does the increased volume of aflibercept 8 mg raise concerns about the potential for elevated intraocular pressure? How do you evaluate and address this in clinical practice?

Panelists discuss how both medications demonstrate favorable safety profiles in clinical trials, with aflibercept 8 mg benefiting from extensive 2-mg safety data, while acknowledging the need to monitor intraocular pressure due to increased injection volume, particularly in at-risk patients.

Outcomes with Raricimab and Choosing Between the New Therapies

In clinical trials, faricimab showed noninferior vision outcomes compared to aflibercept 2 mg. What added benefit do you see by targeting Ang-2?

Panelists discuss how faricimab’s dual inhibition of Ang-2 provides additional benefits in vascular stability and inflammation reduction beyond VEGF-A suppression alone, potentially leading to improved durability and treatment outcomes in selected patients.

Faricimab Molecular Design and Role of Ang-2

What is the unique nature of the faricimab molecule, and what is the clinical rationale for targeting Ang-2 in treating retinal diseases?

Panelists discuss how faricimab’s bispecific antibody design uniquely targets both VEGF-A and Ang-2 pathways, addressing the complementary role of Ang-2 in vascular destabilization and inflammation in retinal diseases.

Dr. Marion Munk examines the Phase 2/3 clinical trial of high-dose aflibercept (8 mg) in diabetic macular oedema.

Efficacy and Safety of Aflibercept  8 mg in PHOTON Trial in DMO

Dr. Marion Munk examines the Phase 2/3 clinical trial of high-dose aflibercept (8 mg) in diabetic macular oedema, presenting key outcomes and clinical implications of the data.

Efficacy and Safety of Aflibercept 8 mg in PHOTON Trial in DMO

Dr. Marion Munk reviews the Phase 3 clinical trial of high-dose aflibercept (8 mg) in neovascular AMD.

Efficacy and Safety of Aflibercept 8 mg in PULSAR Trial in Neovascular AMD

Dr. Marion Munk reviews the Phase 3 clinical trial of high-dose aflibercept (8 mg) in neovascular AMD, emphasizing how this new therapy could alleviate the treatment burden for patients while providing superior outcomes.

: Before we conclude, I would like to get some final thoughts from all of you. Let’s start with Dr Korobelnik. Can you say a few words on the future of dry AMD [age-related macular degeneration]?

 We have seen a lot of research activities for new long-duration treatments in wet AMD and in diabetic retinopathy. There is also a lot of research and developments for advanced dry AMD, for geographic atrophy, and there are currently 2 ongoing phase 3 trials from 2 companies that are looking at inhibition of the complement cascade. We should know later in 2021, or in 2022, [whether] those drugs are beneficial to slow down the progression of the disease. If it works, this will be interesting because it’s a completely unmet need [right now]. We’ll see.

 Thank you. So it’s all about inflammation at this time?

 Dr Moosajee, do you have some concluding remarks?

Mariya Moosajee, MBBS, BSc, PhD, FRCOphth:

 I am truly excited by my field. For the first time in our careers, we can now say that there is an approved gene therapy available for patients with inherited retinal disorders, with a wealth of trials to follow up. I would like to see more genes being covered, and that, at the moment, is still a very costly process, so maybe it’s targeting more common pathways. There are gene therapies that are being developed towards a factor called rod-derived cone viability factor, which essentially helps cones to uptake glucose and to convert that into energy and work better. Hopefully that kind of universal treatment will be able to be accessed by more patients with inherited retinal disorders rather than on a gene-based system. It is a promising field and we will learn a lot from the work that is being done in AMD and diabetic retinopathy, in terms of the devices that you’re using and trialing now, and how we can apply that to our field.

 Thank you. Dr Peto, some words from your side?

 I completely agree that we live in an exciting era of diagnostics and treatment. Something we’ve learned from the pandemic is that patients adapt very well to the new environment. We are now seeing patients over the age of 90 who will happily have a virtual consultation with us. We are seeing people who are using home monitoring devices, and we’re also seeing patients who happily come to virtual clinics where they spend very little time, get images quickly, and then only come back to a busy clinic if they need injections or treatment. We need to learn from these developments, we need to cherish them and go on with providing the best service because this helps us to strategize and restratify our clinics and get everyone to the right clinical pathway.

 Do you think this digital world will reduce the quality? Five years ago we all spoke about multimodal imaging, high-quality images, and combining images from different modalities, just to be more secure and do more sophisticated diagnostics. Now everything is digital. We do images with devices at home, which don’t have the quality as compared with devices in a big hospital, and you can’t combine different images. Do you think the quality will go down a little bit?

 What we need to do is to make sure that the quality of those images that we get supplied with go up. When they started the anti-VEGF [vascular endothelial growth factor] injections, we didn’t have SD OCTs [spectral domain optical coherence tomography], we had time domain OCTs. As soon as more people used them, more people needed to have an OCT, and more people needed more details—suddenly the price dropped, and a lot of new functions appeared. I’m hoping that the home monitoring devices will undergo the same type of development. We must remember that, in a lot of patients, we only need to decide if they need to come in or not, and if they need an injection or not. So we might not need every single time and every bit of imaging that we usually do at diagnosis. If we’re clever about it and we get good images, then we might be able to change the dynamic of a clinic to those who are higher risk.

 We must differentiate between initial visit baseline to make the diagnosis, then we need multimodality and follow-up. For follow-up, OCT probably does it all. So home monitoring with OCT can be promising. We don’t need multimodality on each visit.

 I think that’s why we call it monitoring, because, for diagnostics, you need to get the diagnosis right. They can have all sorts of other diseases that mimic AMD, and old patients with diabetes can have a lot of other diseases as well. We need to establish a secure diagnosis, especially if we don’t see them regularly in the clinic.

 Thanks to all of you and to our viewing audience. We hope you found this 

 discussion to be rich and informative. Thank you very much.

Key takeaways from a discussion on the management of age-related macular degeneration, diabetic macular edema, and inherited retinal disease and insight regarding what to look forward to as the field advances.

Optimizing Care For Patients With Retinal Disorders

 As a concluding remark: We have all been affected by the COVID-19 pandemic, and our retinal practices have changed dramatically. What will last from this experience and from the changes in our practices?

 My cohort of patients were deemed nonurgent in the pandemic. So a lot of the practitioners were told to cancel appointments to allow for capacity for AMD [age-related macular degeneration] and the serious diabetic patients. However, I quickly converted to virtual consultations. Especially in genetics, what we call teleogenetics, is extremely accessible through virtual platforms. Virtual consultations are something that we will continue to do going forward. From an inherited eye disease point of view, we can limit the amount of follow-ups that we give patients and maybe try to reduce that referral to a specialist center, but have joint care with local district general hospitals so patients aren’t traveling so much. Maybe we can introduce home monitoring and use digital technologies moving forward. We can also instigate more diagnostic hubs in local areas, where patients can get their autofluorescence and OCT [optical coherence tomography], then we, as clinicians, can remotely monitor those patients following up with more virtual consultations.

The impact of the COVID-19 pandemic on the management of patients with retinal disorders and considerations for how new practices may be adopted into future practice.

Managing Retinal Disorders: Lessons Learned From COVID-19

Dr Moosajee, can you talk more in depth about gene therapy in retinal disease? I would also like you to address virus and nonvirus approaches; vectors and nonvectors.

 Absolutely. The gene therapy field for hereditary retinal disorders is vast. There are hundreds of trials underway for this, and now the most common vector system that we use is the adeno-associated virus [AAV]. There are gene therapy trials for achromatopsia: 

 is the main genetic cause there. Choroideremia has reached phase 3 and we’re waiting to hear the results of that. These adeno-associated viral vectors have a size limit of the gene that it can accommodate. It can accommodate genes that are essentially less than 4000 bases in size. The smaller genes are fine, but you start to get in trouble with genes that are bigger than that, that are also common causes of these retinal degenerations. For example, 

, which is the most common cause for Usher syndrome type 2, but also one of the most common causes of nonsyndromic retinitis pigmentosa, and that gene is something in the region of 18,000 bases in size. How do we then package these genes to deliver it back into the retina so that we can potentially apply this to more people? There are now a lot of studies going into developing dual AAV vectors whereby we split the gene into components and put them into individual AAV vectors with a linker so that, when it’s translated, you end up forming the complete cDNA [complementary DNA] that can be translated into a protein.

They are now in the development of these nonviral gene therapy vectors. One is a DNA plasmid that has a component called a scaffold matrix attachment region; it essentially will allow any sized gene to be carried, even portions of chromosomes, but this can easily accommodate the 

 gene. These viral vectors are still in preclinical development and have gotten into nonhuman primates as well. However, they are showing relatively long expression—up to a year in mouse studies—and good expression of the protein in the retinas following subretinal injection. There are pros and cons to these new types of vectors. The con is that it doesn’t have the infective capability of a virus. We may need to start to use some of the devices that you talked about, like the microneedles or micro-electroporation systems that you’re developing for AMD [age-related macular degeneration], etc, to help these vectors enter into photoreceptors. The pros are that it can carry a gene of any size. They don’t have any viral components, so you’re going to reduce your chance of an immune response. They don’t integrate into the genome, so you reduce your chances of incisional mutagenesis. These specific components, like these S/MARs [scaffold/matrix attachment regions], which are naturally found within our own chromatin that help it to bind, prevent these vectors from being silenced and allow them to replicate extra chromosomally. These are coming into the future that may be the next generation of gene delivery vehicles as we go forward.

Thank you. This was very interesting. The nonviral vectors have a better safety profile and larger cargo capacity, and they have the potential for repeated administration. Sooner or later, if we can overcome the major drawbacks, maybe nonviral vectors will be available, at least for retinal diseases. Do you have experience with the first retinal gene therapy, the Luxturna from Spark Therapeutics? 

 Yes. This is the adeno-associated viral vector that has now been approved by the FDA and the European Medicines Agency. It is approved by our NHS [National Health Service] and is available to patients, and there are sites all over the world offering this. So far, we have seen positive results. This viral vector was approved on the multi-luminance mobility maze test, where we classically see the patient at baseline. Then a year after treatment, where they’re able to navigate through the maze at 1 lux level successfully in a short period of time. In the UK [United Kingdom], my experience with pediatric patients and adults who have now had this, we are seeing a stability, if not improvement, in the children with their visual acuity and their vision in dim light, and also in improving navigational vision for older patients. The hope is that if we can also potentially deliver these genes through intravitreal, we might reach more parts of the retina because, at the moment, we’re just going for the area where we apply the bleb, and there are still islands of retina in the periphery that would be beneficial if we could treat these with the gene therapy. There is still a lot of work to do and a lot of progress to be made in general in trying to optimize the results of these gene therapies.

Dr Mariya Moosajee comments on the next generation of gene therapy for inherited retinal disease and highlights various systems under investigation.

Future Gene Therapy for Inherited Retinal Disease

The dexamethasone implant was the first approved drug therapy for retinal vein occlusion. At this time, we had no anti-VEGF [vascular endothelial growth factor] drugs approved, and dexamethasone was the first medical treatment. Before dexamethasone, we only had laser treatment. I would also like to mention the AR-13503 [SR implant], which is an inhibitor of Rho kinase and protein kinase. It is also a sustained-release implant, which is currently being investigated for the treatment of wet AMD [age-related macular degeneration] and DME [diabetic macular edema]. It is the first in ongoing human study of the safety of this implant. We cannot add more information at this time on this drug clinically because it’s still in phase 1. That’s why I would like Dr Korobelnik to say a few words on axitinib intravitreal implant, which is a sustained-release tyrosine kinase inhibitor. We don’t know much about this pathway so far. If we can at least antagonize it sufficiently to reduce the VEGF expression—maybe you can say a few words on this, Dr Korobelnik.

 I think you have said everything, Albert.

It is an anti-VEGF biopolymer conjugate, and an ongoing phase 1 trial, so we only have interim…

 It’s more advanced. Phase 2 for KSI-301 is positive, so they are now recruiting for phase 3. It’s interesting because we know VEGF inhibitor very well. This is a combination of a VEGF inhibitor plus a biopolymer, allowing a slow release of the inhibitor. It is promising. In the trials, they are exploring 1 injection every 24 weeks, so 1 every 6 months. If it works and is safe, that would be interesting, because it is a gel injection, so it should be safe. KSI-301 is a promising long-lasting VEGF inhibitor. I look forward to the phase 3 results.

Then you have to say a few words about inflammation and KSI.

 Of course, it’s the same for all the devices. They may induce intraocular inflammation. Some may be related to debris, to the polymer, or to something that is going to last longer and induce immunogenicity, as we’ve said before. For safety regarding the drug, intraocular safety is something that we have not been using with the 3 old VEGF inhibitors that we have at the moment, so it’s something new. It’s not only intravitreal inflammation, but it’s also retinal inflammation and vasculitis that we have seen with brolucizumab. Now everybody is aware of that risk and is looking carefully at the safety of the retinal surface and in the retina for any new compound.

That is why I am not so euphoric, and a little skeptical, especially when we inject the gel into the eyes. Let’s wait and see for phase 3. This is always the conclusion, if we speak about drugs and drug development.

Considerations for treating retinal disorders with sustained-release drug delivery implants in an effort to address current treatment challenges in the field.

Sustained-Release Drug Delivery for Retinal Disorders

 We will move forward and speak a bit about some investigational delivery systems. Let’s start with the…system, which is a suprachoroidal administration device being investigated for triamcinolone acetonide. Dr Korobelnik, can you say a little bit about the results from phase 3 and the treatment strategy in general?

 Yes, there are 2 good points about this option. No. 1, it is a steroid; we are very familiar with steroids. No. 2, it is not in the vitreous cavity, it is suprachoroidal. We probably do not expose the patients to the risk of intraocular infection; these are very positive. It seems that the drug can still go through the retina and be very effective. Of course, we are concerned about the fact that the drug may go through the anterior segment and induce elevated intraocular pressure. Phase 3 trials are, as far as I know, ongoing, and we will look at those results very carefully, both on efficacy and safety. I think it’s interesting; it is something really new that may be an option and a true competitor compared to intraocular steroids.

 Yes, thank you. At least the way of administration is much easier than in former times where we had to use a catheter. It is quite easy in terms of the surgical approach, so let’s wait and see. Again, the portal delivery system [PDS], just a few more words on this. The FDA application can be expected soon and further countries in the next year or so. Dr Peto, can you speak a little about the ranibizumab port delivery system? We expect that it will deliver the drug for about 6 months; it should be at least equal to injections. Maybe a few words on the ongoing studies?

 The results are very promising, and that is why we’re expecting reasonably soon that it might be available. It is a refillable system; we will be able to use the same port to give the patient the next dose of the drug, instead of an injection. And every 6 months we would potentially have to see the patients. If we do use this in diabetes, we must think about what happens to the retina and potentially the anterior segment for neovascularization in between. We’ve got to make sure we have relatively good protocols for not [seeing] any patients in between. Because those patients who have had a lot of injections are very used to coming regularly. They might struggle with not being seen as much even if they will enjoy the freedom from the eye clinics. We are looking forward to this delivery system, and we’re looking forward to injecting must less than we do now.

 If I may make a short comment on the PDS; it is very promising. I agree Tunde, however, there is a problem as you said earlier, that it is a surgical procedure to put the reservoir in. You need a vitreoretinal [VR] surgeon, and you need an operating room. VR surgeons are very busy, and operating rooms are very busy; it is going to be a challenge. I cannot imagine implanting reservoirs in many patients. This very practical first step to put the reservoir in the eye is going to be problematic in many places.

 I completely agree; that is why I said that we got partly what we wished for, and then we have new challenges we need to overcome. It will be suitable for a subset of patients who cannot get there regularly, and who are struggling with the injections. But I agree, we do not have enough vitreoretinal surgeons to do the operations.

 That is due to them all being busy with injections, and so on. In [previous] times it was much easier. In the interest of time, we will move forward. I would like to have a few words on sunitinib. This is a vascular endothelial growth factor inhibitor applied by means of a microparticle depot. Phase 2A is already completed, macular edema secondary to RVO [retinal vein occlusion]. For phase 2B, we have interim results available, which are also at least a little promising. Dr Korobelnik, can you say a few words on this?

 I do not have personal experience with this new way to deliver drugs. I think that a lot of companies are exploring a way to answer our problem, which is increasing durability of both steroids and VEGF inhibitors. We are looking for long duration, so anything that can help provide a longer duration is fine. I am very careful with phase 1, phase 2A and 2B results. We need to look really in detail at the protocols in the results to be sure that it is promising. Also, investors will have to look at the results before going to phase 3. However, I do not have personal experience with that.

 Dr Peto, do you know a little more about the competitor for Ozurdex, [intravitreal dexamethasone], which is also biodegradable, for patients with macular edema due to vein occlusion or diabetes? The safety and proof of concept study is completed. Do you know a little more that you would like to share with us?

 This is the first time that retinal vein occlusion has come up today, and this is a very common problem for the elderly population. However, we also see it in younger people as well. In the UK, we can only give a lot of the steroid products to patients who are pseudophakic. It will be interesting to see if some of these new biodegradable and erodible products might be useful for those who are slightly younger and who might be phakic as well. This would be a new way of looking at it, because you do not have the vessel that takes the drug there, and it would completely erode away. Repeated injections might be less of an issue, and you might have less of a problem as to what to do after 2, 3, or 4 injections if it is an ongoing problem.

An overview of delivery systems under investigation for retinal disorders and implications for future use.

Delivery Systems in the Pipeline for Retinal Disorders

 I would like to briefly review some of the promising new agents. Let’s start with faricimab. I believe this drug is about to be approved in the near future. Dr Peto, would you like to say a little bit about this drug?

 Yes. Faricimab is a drug that has been trialed in both DME [diabetic macular edema] and neovascular AMD [age-related macular degeneration]. The results were reported earlier this year [2021] in February at the Angiogenesis, Exudation and Degeneration symposium, and then at ARVO [the Association for Research in Vision and Ophthalmology annual meeting] as well. The different studies covered both diabetic macular edema and neovascular AMD; about half of the people who received faricimab could be treated every 4 months in the first year. We see that based on the dosing regime, it seems that you can give potentially fewer injections than you would have done otherwise. Of course, real-world data will be required to see if the drug trial regimen will hold up just as well in real-world evidence. The patients who were treated with the drug faricimab showed rapid and consistent improvement in anatomical outcomes, including that the central subfield thickness was much lower than in the comparator, and the retina did dry out relatively quickly and then remain dry. We are going to have to see if and when they would be able to use it, if it can mimic the clinical trial findings. If the patients could go out to 4 months, even in the first year, that would make a huge difference to our clinical burden, the burden on the patients, and the burden on their caregivers and society as well.

 Thank you very much. I think it’s a very promising and interesting approach at least. Dr Korobelink, conbercept was approved in China in December 2013. Now since December last year, it is in Phase 3 trials for FDA approval, and I believe it will come to the European community sooner or later as well. Can you give some brief words on conbercept?

 In fact, it is not as good as you said, Albert. I agree that it has been approved in China for almost 10 years. The company decided to do phase 3 trials for AMD, and they just failed to reach noninferiority. They decided to interrupt the trials a couple of months ago because the patients exposed to conbercept were not doing as well as those exposed to the comparator. At the moment, all of the trials are stopped. The company thought that they would not get the drug approved based on those results. I think conbercept is going to stay in China, but I’m not sure that it will come to the rest of the world, unless there is an understanding of the failure of these phase 3 trials. This is a big disappointment, by the way.

 That’s what I wanted to hear, thank you very much. Can we continue and give a few words on DARPins [designed ankyrin repeat proteins]?

 For DARPins, it’s a bit the same; many people were very enthusiastic about the capacity of those compounds to be very effective. Unfortunately, there were both efficacy and safety issues; to my knowledge, so far the DARPins are not being developed for use in intraocular injections. It’s the same for abicipar, which was a very promising agent that unfortunately did not reach the safety bar. The efficacy was OK, but the safety was not. There was a lot of intraocular inflammation, around 10% to 15%, which is simply not acceptable compared to what we have available to inhibit VEGF at the moment.

 Ripasudil is a completely different approach. Can you briefly speak about this?

 I think the protein kinase inhibitors are a new pathway that may be interesting in treating patients with DME and wet AMD. However, an interesting pathway does not mean it will be feasible. We need to have strong results from clinical trials; I know they are ongoing, but there are not yet very convincing results. We must wait a little.

 There is nothing out there that is convincing.

 This pathway was addressed nearly 20 years ago. The oral drug was not successful, so we have to wait. I am not convinced, but at least I wanted to mention it. Let us move a bit forward and briefly say a few words on axitinib. Dr Korobelnik?

 As Tunde said, I do not have that much experience on that pathway and drug. I know it is an oral treatment. Oral is very interesting for patients with diabetes who have a lot of visits; it is challenging for them to attend the visits and injections in an ophthalmology clinic. Getting an oral drug that would reduce DME would be fantastic. But once again, I follow the companies that are developing those drugs based on interesting pathways, and what I need to see are strong clinical data, which I am missing currently.

 Tyrosine kinase inhibition was also investigated many years ago, and so far it has not been successful.

 Yes, the pathway is interesting, but maybe there was an issue with the dose or with the…of the drug?

 Dr Moosajee, could you say a few words on antisense oligonucleotides for LCA [Leber congenital amaurosis] and Usher [syndrome]?

 Absolutely. There are trials underway where we are employing these antisense oligonucleotides. These are essentially a string of nucleotides that bind to the corresponding RNA and then block the translation of a particular exon or a cryptic splice site. For example, for 

, these oligonucleotides will prevent exon 13 from being translated, so you get the full usherin protein but lacking exon 13. So far, there have been phase 1/2 clinical trials, and it’s showing that there may be a positive effect in stabilizing the patient’s vision. This is given through an intravitreal injection. It should be moving on to phase 3 clinical trials and maybe thinking about more regular dosing, with 1 injection every 6 months. There has also been the clinical trial for LCA targeted toward 

, which has also shown favorable results and is moving to phase 3 as well.

A discussion highlighting new agents under investigation for retinal disorders and implications for future use based on data revealed in more recent clinical trials.

AMD

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