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Videos

Angiogenesis, Exudation, and Degeneration 2021 Virtual Symposium highlights and thoughts on current treatments options for DME and exudative AMD are discussed. 

Angiogenesis 2021 Virtual Symposium Takeaways & Final Thoughts 

Aleksandra Rachitskaya, MD, speaks on the current gaps in AMD treatment as well as ongoing retinal advancements to help address unmeet needs of patients.

Addressing gaps in treatment of AMD

Anat Loewenstein, MD, provides an update on the latest developments in emerging therapies for the management of age-related macular degeneration (AMD) and wet AMD. 

Emerging therapies for AMD management

Joshua Mali, MD, discusses the three major risk factors for developing age-related macular degeneration (AMD). 

Examining 3 major risk factors of AMD

Ian C. Han, MD, assistant professor in the Department of Ophthalmology and Visual Sciences, Institute for Vision Research, University of Iowa Hospital and Clinics, dives into the basics of age-related macular degeneration (AMD) and what patients need to know.

Learning the basics of age-related macular degeneration 

The investigators noted that this report is the first about subretinal drusenoid deposits in Black and Hispanic patients with age-related macular degeneration

AAO 2025: Subretinal drusenoid deposits in Black and Hispanic patients with AMD

Patient response focused on perceived vision-related quality of life outcomes, investigators said

Intravitreal complement inhibitor treatment for GA viewed favorably by patients 

The newly-approved technology delivers low-dose microcurrents through closed eyelids to stimulate retinal cells

MacuMira launches first Health Canada-approved device for AMD treatment

Alteogen received a positive CHMP opinion for EYLUXVI in July 2025

European Commission grants marketing authorisation to aflibercept biosimilar EYLUXVI (ALT-L9)

Presentation topics will include therapies for age-related macular degeneration, X-linked retinitis pigmentosa and other retinal pathologies

EURETINA industry previews: Beacon Therapeutics, Nanoscope Therapeutics and Valitor

Arshad M. Khanani, MD, MA, FASRS, shares GA results from the GATHER2 extension trial during the 2025 American Academy of Ophthalmology meeting

This year's American Academy of Ophthalmology (AAO) meeting is being held in Orlando, Florida. Ahead of the meeting, Arshad M. Khanani, MD, MA, FASRS, spoke with Sheryl Stevenson, Executive Editor of the Eye Care Network, about results from the GATHER2 extension trial. The extension trial, like the Phase 3 GATHER2 trial, evaluated avacincaptad pegol (ACP) in the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

GATHER2 met its primary endpoint at 1 year. In the open-label extension, patients were given ACP monthly for 18 months, whether they previously received ACP or sham. All patients had an opportunity to enroll in the extension, Dr Khanani said.

"The key results are the efficacy and the safety data," he said. "There's no sham control, so we compared it to a projected sham. When you look at patients who were on ACP before the open-label extension...that resulted in 40.5% reduction of GA lesion growth [in that group], compared to projected sham." Patients who had previously been in the sham arm for 2 years, after being enrolled in the extension and receiving ACP, experienced a 37.1% reduction in lesion growth. Dr Khanani noted that the benefits of ACP and impact on lesion growth reduction seemed to start early. The findings, he said, indicate that earlier treatment with ACP will lead to improved performance over time.

Watch the full video to learn more about the clinical implications of this research.

Dr Khanani shared his first-time results talk during an AAO specialty day

AAO 2025: Arshad M. Khanani, MD, MA, FASRS, shares GA results from the GATHER2 extension trial

Dr Borkar, a vitreoretinal surgeon at Duke University, spoke to the Eye Care Network about her American Academy of Ophthalmology (AAO) presentation

Durga Borkar, MD, on avacincaptad pegol as routine care for geographic atrophy

Ahead of AAO 2025, Jean-Francois Korobelnik, MD, shared highlights from the PULSAR extension study on aflibercept 8 mg and fluid resolution in age-related macular degeneration

 Ahead of the 2025 American Academy of Ophthalmology (AAO) meeting in Orlando, Florida, the Eye Care Network spoke with Jean-Francois Korobelnik, MD. Prof Korobelnik, of Hôpital Pellegrin and CHU de Bordeaux, Bordeaux, France, is an editorial advisor for 

This year, he is a co-author of a poster on the PULSAR extension study, assessing aflibercept as a therapy for neovascular, or wet, age-related macular degeneration (AMD). The research examined fluid resolution in treatment-naive patients with nAMD receiving aflibercept 8 mg, or those patients who were making a switch from 2 mg to 8 mg aflibercept. The full poster was presented by Marion Ronit Munk, MD, PhD, during the congress.

In this video, Prof Korobelnik discusses the fluid resolution outcomes observed in the study, describes the accompanying functional outcomes and patient response, addresses possible areas of future study and shares his perspective on the changing landscape of retinal therapies.

Jean-Francois Korobelnik, MD, shares highlights from the PULSAR extension study showcasing aflibercept 8 mg and its ability to promote fluid resolution

AAO 2025: Jean-Francois Korobelnik, MD, shares highlights from the PULSAR extension study

Jay Chhablani, MD, shares late-breaking data from the ArMaDa trial, investigating gene therapy for Geographic Atrophy and dry age-related macular degeneration, at EURETINA

At the 2025 European Society of Retina Specialists (EURETINA) congress, Jay Chhablani, MD, shared new gene therapy findings in a symposium focused on late-breaking data. Dr Chhablani is vice chair of clinical trials at the University of Pittsburgh Medical Center Vision Institute in Pittsburgh, PA.

Following the EURETINA meeting, Dr Chhablani sat down with Hattie Hayes, editor of 

, to discuss those results, which stemmed from the Phase1/2 ArMaDa trial. The ongoing ArMaDa trial is investigating OCU410 (Ocugen), a novel modifier gene therapy for geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). The late-breaking results pertained to safety and efficacy findings, and Dr Chhablani indicated that plans for a Phase 3 study are underway. More information on ArMaDa Phase 3 is expected in 2026.

In this conversation, Dr Chhablani discussed the study design. Phase 1, a dose escalation study, enrolled patients in low-, medium- and high-dose groups. Meanwhile, Phase 2 was a dose expansion study. He reviewed inclusion critera, including GA lesion size, and primary safety outcomes. Watch the full video to learn about the reported results, which include slower GA lesion growth and early indications of functional improvement.

Dr Chhablani said "having multiple approaches to the same problem" is key for reaching the maximum number of patients with age-related macular degeneration

EURETINA 2025: Jay Chhablani, MD, provides an update on gene therapy for AMD and GA

Editorial advisory board member Alexandra Miere, MD, PhD, speaks about the ACTOR and HERMES studies at the 2025 European Society of Retina Specialists (EURETINA) Congress

During the 2025 European Society of Retina Specialists (EURETINA) congress, 

 spoke with editorial advisory board member Alexandra Miere, MD, PHD. Dr Miere is an associate professor of ophthalmology, Université Paris-Est Créteil, France, and she is also an honorary research fellow in medical retina at Moorfields Eye Hospital, London.

Dr Miere presented findings from the ACTOR and HERMES studies, both published in the EURETINA journal. The ACTOR study investigates vascular remodeling in patients with neovascular age-related macular degeneration (AMD) who have been treated with ranibizumab. The HERMES study focuses on perfusion changes over 24 months in patients with central retinal vein occlusion (RVO). 

Speaking about the prospective ACTOR study, Dr Miere said, "We tried to capture if the vascular remodeling could be predicted for exudative recurrence on [spectral domain optical coherence tomography] SD OCT in the month following the OCT angiography."

"This is a question that has puzzled retina specialists since OCT angiography [OCT-A] has been has been introduced," she explained. "The short answer is no...However, OCT angiography brings other types of information. The two imaging modalities [structural OCT and OCT-A] are complementary and should be used together in our nAMD patients." Neovascularisation remodeling and exudation may not have a causal relationship in cases of nAMD, Dr Miere said, but both provide vital information about the disease and its impact on the retina.

The HERMES study examined perfusion in patients with central RVO. Patients were treated with aflibercept and monitored for 24 months. "In these patients, what we noted by doing ultra-widefield fluorescence angiography and OCT angiography was that, on ultra-widefield fluorescence angiography, the peripheral non-perfusion worsened during time, and we had a very important increase in the ischemic index in these patients with RVO," Dr Miere said. However, despite these findings in the peripheral retina, in the central area, the vascular density on OCT angiography remained stable, she said. "So even though we have a stable visual acuity, and the stable vascular density in the macula area in patients with RVO, we should also always, always, always check the periphery," she emphasised. A worsening in non-perfusion in the periphery can result in potential complications, she warned.

To learn more about the potential risks of peripheral non-perfusion, and hear Dr Miere share her predictions for the future of machine learning in ocular care, watch the full video above.

Dr Miere presented the ACTOR study, illuminating vascular remodeling in patients with neovascular AMD, and the HERMES study, investigating perfusion changes in central retinal vein occlusion

Editorial advisory board member Alexandra Miere, MD, PhD, presents two studies at EURETINA

During the 2025 EURETINA congress, the Eye Care Network spoke with Mark Gillies, MD, PhD, director of research at the Save Sight Institute, about anti-VEGF agents.

During the 2025 congress of the European Society of Retina Specialists (EURETINA), the Eye Care Network spoke with Mark Gillies, MD, PhD. Prof Gillies is affiliated with the University of Sydney, where he is the director of research at the Save Sight Institute. He also leads the Fight Retinal Blindness! Registry, a global database of clinician-reported patient data.

Established in 2007, the registry tracks outcomes of anti-VEGF injections. Today, over 150 practitioners from 20 countries in Australia, Asia and Europe enter their patient data into the registry.

"The unique thing about our registries is we identified a minimum prospectively-identified outcome set that has to be tracked at every visit. If you try to finalise the data without entering all the in-range fields, then it won't accept it, and it tells you what you have to fill out. So, you get 100% quality data from every visit, for every patient, for the last 20 years. With this, we've been able to do many analyses," Prof Gillies said. "We've published about 100 publications over the last 15 years, and we distinguish ourselves from the other registries because they tend to scrape data. So the IRIS registry, for example, will just scrape electronic medical records, but they don't get complete data from every visit."

At the 2025 EURETINA meeting, Prof Gillies presented research findings on next-generation VEGF inhibitors, including Eylea HD and Vabysmo. "These things become stronger as you go," he noted. "So at the moment for Vabysmo, we have 2 years [of data], and for high dose Eylea it's just 1 year. But in 3 or 4 years, it will have really good amounts of data so that we can tell which drug is going to be best for which patient. We will also track the biosimilars as they come out. They haven't really been through such a thorough evaluation process, but we'll be tracking them just like the other drugs, and we'll see whether they really are as efficacious as they claim to be and as safe as they claim to be."

To learn about the research findings Prof Giliies presented at this year's EURETINA meeting, watch the full video.

Today, over 150 practitioners from 20 countries in Australia, Asia and Europe enter their patient data into the Fight Retinal Blindness! Registry

Mark Gillies, MD, PhD, introduces the next generation of anti-VEGF agents

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.

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

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.

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