2022 RETINA SUMMIT CONFERENCE RECAP
The Cole Eye Institute Retina Summit, held on April 30, 2022, included didactic presentations and discussions from renowned retina specialists, focused on recent clinical study results and their application to clinical practice.
NEW FRONTIERS IN AMD AND DME – SESSION HIGHLIGHTS
Katherine Talcott, MD opened the session on AMD and DME with a comprehensive review of recent advancements in dry AMD treatments, focusing on the exciting pipeline in this area of great unmet need. Dr. Talcott noted that despite significant advances in the treatment of neovascular AMD, treatments for geographic atrophy (GA), an advanced form of dry AMD characterized by the loss of photoreceptors and retinal pigment epithelium (RPE), remain elusive.
The good news is several potential treatments are currently under investigation, targeting different pathways including complement inhibition, antioxidative stress, anti-inflammatory agents, visual cycle modulators, and gene therapy.
Some of the treatments in later stages of development include two agents that block the complement system, which when activated can lead to inflammation and cell death, and has been implicated in GA by human genetics studies.
Pegcetacoplan is a pegylated cyclic peptide inhibitor of complement C3 which has shown in recently completed studies the potential to become the first approved treatment for GA. Another pegylated complement inhibitor, avacincaptad pegol, inhibits complement C5 and has also shown in a recently completed phase 3 study to reduce lesion growth in patients with GA. A second phase 3 study is underway. Other therapies in earlier stages of development with phase 2 studies underway were discussed, including ANX007, which inhibits C1q early in the classical pathway, and IONIS-FB-LRx which is a novel specific antisense oligonucleotide that targets the complement factor B gene.
Anti-inflammatory agents and visual cycle modulators under investigation include FHTR2163 (Genentech/Roche) is a novel antibody directed against high-temperature requirement protein A1 (HtrA1), and LK-001, a chemically modified vitamin A to slow the formation of toxic vitamin A dimers. And in gene therapy, a one-time AAV-based gene therapy designed to rebalance an overactive complement system by expressing the complement factor I (CFI), was discussed and is currently being evaluated in two Phase 2 trials.
Peter K. Kaiser, MD presented latest developments on the area of biosimilars, reviewing some of the key aspects related to pathways for drug approval and how they differ for biosimilar products. He noted that although potentially shorter than the development process for reference biologics, the development of biosimilars is rigorous and involves a time investment of 5 to 9 years or more and development costs of greater than $100 million. The extrapolation of indications, that is, the use of biosimilar to treat conditions for which the biosimilar was not necessarily studied but the reference biologic is approved, was discussed. For instance, a ranibizumab biosimilar could only be studied in neovascular AMD, but approved for all ranibizumab indications. The nomenclature of biosimilars was also addressed as it varies based on different guidelines (e.g. WHO gives unique “Biologic Qualifier” while the FDA gives random four-letter “devoid of meaning” suffix and the EMA requires no name change). Importantly, the safety of biosimilars is an important consideration, and will be important to consider as a number of anti-VEGF biosimilars are being evaluated.
Daniel F. Martin, MD provided an in-depth discussion of the DRCR studies, emphasizing the key unanswered questions in AMD and providing the rationale for why some trials of interest have not been done by the DRCR Retina Network. The presentation provided an overview of the evolution of the DRCR network, which now includes approximately 1800 members and has completed more than 36 multicenter studies, noting that very few ideas for trials ever make it to a full study (only 1 in 20). Some of the trial ideas that did not become full trials included:
• Should anti-VEGF injections be given to prevent exudative MNV in eyes with high risk non-exudative AMD?
• Should AREDS supplements be continued when the second eye develops nAMD?
• What is the optimal management of large subretinal hemorrhage in eyes with nAMD?
• Could statins be effective for drusen regression and prevention of advanced AMD?
• Should I use Treat and Extend or PRN as my anti-VEGF treatment algorithm?
Dr. Martin noted that some of the reasons for not conducting some of the proposed trials include the fact that, in some cases, the estimates of clinical efficacy are low. Additionally there are challenges in defining the primary outcome, the disease prevalence might be low with variable presentation, or the current standard of care makes enrolling a representative population impossible.
IMAGING AND SURGERY – SESSION HIGHLIGHTS
The imaging and surgery session was focused on the cutting edge developments in the field, including home AMD monitoring, deep learning and artificial intelligence applications, and learnings from the COVID-19 pandemic.
Andrew W. Browne, MD, PhD, discussed the impact artificial intelligence has had in the field of ophthalmology, focusing on deep learning as a tool for vitreoretinal surgery. Dr. Browne noted the powerful application of artificial intelligence in the classification and localization of lesions. Tools for labeled data collection and assessment during surgery are in development, and have the potential to revolutionize the field by providing accurate methods for identifying and tracking surgical instruments in the 3D vitreous space.
Yasha Modi, MD, presented practical applications of OCTA in clinical practice, emphasizing some of the good applications of this important technology as well as some challenges faced by retina specialists. Some of the potential issues to watch out for included motion and projection artifacts, which may be interpreted as CNV and may impact the accurate visualization of the vessels. Dr. Modi presented his framework for considering OCTA, which included the following:
• Reject or repeat image acquisition with high projection or motion artifact
• Use cross-sectional flow overlay and compare to en face imaging.
• Run through the cube if you are lost.
Adding that for retina specialists still in training, “a test shouldn’t be ordered if you don’t know what to do with the answer.”
Some of the important features that can be captured and identified using OCTA include nonperfusion, neovascularization, and vessel remodeling. Importantly, OCTA can also be crucial in differentiating neovascular nonexudative AMD, non-neovascular AMD with fluid, and neovascular AMD with exudation, allowing precision when diagnosing these patients and determining when to treat.
Sunir J. Garg, MD, FACS, highlighted some of the changes in retina practice brought on by the COVID-19 pandemic, discussing which of those changes are likely to stay. Of interest, the use of povidone iodide as an important preventive measure for infections was highlighted, with the use of aqueous chlorhexidine described as a possible alternative antimicrobial for ophthalmic procedures like intravitreal injections. Some of the studies investigating the impact of the use of masks and the correlation with the development of infections after intravitreal injections were also discussed. The results suggest that mask use does not seem to impact the overall rate of endophthalmitis, although they do seem to prevent culture positive endophthalmitis.
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