June 4th Virtual Meeting Recap

INNOVATE RETINA virtual meeting took place on June 4, 2022, and focused exclusively on game-changing innovations in medical and surgical retina care.



David Brown, MD opened the session on Delivery Challenges for Retinal Therapeutics with a discussion around viscosity and intraocular drug injections, raising the question of whether increased viscosity of retinal therapeutics could present challenges for delivery. A number of therapies recently approved (e.g. faricimab) or under investigation (e.g. pegcetacoplan) have a relatively high viscosity and understanding implications of these differences is important. Some of the key factors discussed include the length as well as the diameter of the needle used, with larger diameters allowing easier delivery of more viscous fluids, and the temperature of the liquid, with warmer liquids having decreased viscosity.

Lejla Vajzovic, MD discussed surgical approaches to viral vector-based anti-VEGF therapies, noting that the eye is a particularly suitable target for gene therapy agents, with a large number of clinical trials currently investigating therapies for inherited retinal diseases as well as other more common retinal conditions. Viral vectors are the most commonly used tools used for gene therapy delivery, and a number of methods and targets for delivery were discussed, including the suprachoroidal space, the vitreous chamber, and the current gold standard method of delivery which is the subretinal space. Additionally, current ongoing trials were discussed, including ongoing trials investigating subretinal and suprachoroidal delivery of novel viral vectors for delivery of an anti-VEGF Fab protein. The details for preparation and administration of subretinal delivery were emphasized, including the injection set up details, and crucial steps for both the vitrectomy portion and the subretinal injection, highlighting that preparation is the key to the success of surgical gene-therapy delivery.

John A. Wells, III, MD discussed differences in currently available anti-VEGF therapies, and in particular, whether the recently approved therapy faricimab is more durable than aflibercept for the treatament of nAMD and DME. He noted that more durable treatment options are needed given the burden of monthly injections that are needed for effective results, and a number of strategies are being investigated to address this unmet need. The trial design and results for comparison studies between faricimab and aflibercept were reviewed, with a focus on some of the differences between treatment regimens, including the number of loading doses and treatment frequency. Although results showed comparable visual acuity and anatomic outcomes between groups with less frequent dosing with faricimab, it was noted that treatment for the aflibercept group was per label and did not allow for less frequent dosing, emphasizing that real world data will be needed to confirm the results observed in clinical trials.


Nancy Holekamp, MD, opened the second section presenting preliminary results from a first-in-human phase I/II gene therapy trial investigating subretinal delivery of GT005, an AAV-2 based gene therapy designed to induce expression of complement Factor I (FI) in patients with geographic atrophy (GA) secondary to AMD. Dr. Holekamp noted that complement inhibition is a validated approach for the treatment of GA given recent clinical trial results with intravitreal injection treatments that inhibit complement activation, adding that complement Factor I has been shown to be strongly associated with the development of AMD, with FI supplementation potentially being able to reduce complement activation regardless of underlying genetic risk. Preliminary results showed that GT005 dose levels have been well tolerated with increased FI levels in vitreous and downstream modulation of complement biomarkers.

Rahul Khurana, MD, presented an interim update on the suprachoroidal RGX-314 program, noting that the suprachoroidal approach may allow more targeted gene therapy delivery and potentially provide a safer approach compared to intravitreal and subretinal delivery methods. Results from the Phase II AAviate study in patients with nAMD showed that RGX-314 was well tolerated, with a similar incidence of intraocular inflammation among cohorts with dose escalation, and that RGX-314 treated patients had stable vision and retinal thickness with a meaningful reduction in treatment burden. Interim results for a small group of patients from the ALTITUDE study were also presented, showing that RGX-314 was well-tolerated in patients with DME, and that 47% of patients treated with RGX-314 showed a greater than or equal to 2 step improvement in disease severity. These results highlight the exciting potential of having a one time, in-office injection of gene therapy that could potentially provide long-lasting improvement in diabetic retinopathy severity.

Rachel Huckfeldt, MD, PhD provided an update on one of the gene therapy programs for the treatment of retinitis pigmentosa, reviewing results from a phase I/II trial of AAV5-RPGR gene therapy. Safety results showed that the majority of adverse events were ocular, related to the surgical procedure and transient. Retinal sensitivity was evaluated by static perimetry and improvements were observed when comparing treated vs untreated eyes 1 year post-treatment. Additional data collection is ongoing with data from a dose-expansion cohort expected to provide further insight into the effectiveness and safety of AAV5-RPGR.

Dante Pieramici, MD provided an update on a novel gene therapy product that is being investigated for the treatment of neovascular AMD. The candidate product, called 4D-150 was identified using a platform for vector evolution that identified vectors with improved expression in retina cells, and includes a dual transgene that inhibits four distinct VEGF family members. In in vitro and nonhuman primate models, 4D-150 resulted in expression of high levels of anti-VEGF product, with no evidence of uveitis or retinal abnormalities. A first-in-human clinical trial has been initiated in patients with wet AMD receiving anti-VEGF treatment.


Yannek I. Leiderman, MD, PhD, opened the third section with a review of artificial intelligence-guided ophthalmic microsurgery, discussing whether it is a disruptive new technology or an extinction event. The presentation included a definition of surgical guidance, as well as an overview of the milestones for AI clinical applications in retina, including a groundbreaking study that reported prediction of risk factors by deep learning analysis of fundus images. Four categories of tools were discussed: enhanced image visualization, surgical templates, tissue- and tool-tracking, and laser delivery. AI based collision avoidance was noted as having potential utility for the fluidics engine, allowing improved performance and reducing the risk of iatrogenic breaks. In summary, it was noted that AI is much better than humans at some image-based tasks, but not all tasks and especially in the medical field where the stakes are very high.

Caroline Baumal, MD, reviewed the future of enhanced surgical visualization, noting that visualization is one of the most critical components of vitreoretinal surgery, with recent advances allowing 3D visualization as well augmented reality displays. The key drivers of these advancements include the need for increased magnification, need for a guide for complex procedures, immersive teaching, and improved ergonomics for surgeons. Systems with 3D heads up display technology reviewed included the NGENUITY and the ARTEVO 800 systems. The Beyeonics One system was also discussed, which includes a headset for augmented reality visualization and allows for surgeon head gesture and foot pedal control for focusing or zooming.


Diana Do, MD, discussed clinical trials and how clinicians can shape clinical programs, highlighting that several clinical trials have had negative readouts but those should not be seen as failures. The most common reasons for negative results discussed included inability to demonstrate efficacy due to a flawed study design or an inappropriate statistical endpoint, and/or the inability to demonstrate safety. Importantly, however, it was noted that a negative readout is not always a bad outcome, as it can lead to greater success in the future and important lessons that can be applied to future trials.

Thomas Ciulla, MD, MBA highlighted and discussed suprachoroidal delivery methods for clinicians, including multimodal imaging, and potential drivers of durability and bioavailability. It was noted that suprachoroidally injected drug levels are similar peripherally and centrally both at the level of the retina and at the level of the RPE-choroid-sclera, highlighting the potential to address macular disorders with the delivery of an in office suprachoroidal system.

Stephen Smith, MD, closed the program by briefly reviewing the upcoming event planned to take place in person at AAO 2022, which will focus on panel discussions with audience involvement. The upcoming event will aim to fill the unmet need of achieving more clinician involvement in industry research and innovation, providing small group sessions that focus on innovation and entrepreneurship for the retina community.


Video sessions from the virtual meeting are available
to view on-demand now via the link below!

Taking place live in-person in Chicago prior to AAO on
Thursday, September 29, 2022