In this episode of the BroadEye Podcast, hosts Shawn Maloney and Dr. Bruno Fernandes welcome Prof. Michel Michaelides, one of the most active clinical researchers in ophthalmology today. Prof. Michaelides leads a large inherited retinal disease clinic—seeing 30–40 children and adults each week—and splits her time between patient care, advanced imaging research, and steering more than ten ongoing clinical trials.

Why This Matters Inherited retinal diseases affect hundreds of thousands worldwide, and for most there is still no approved treatment. Over the past two years, we’ve seen multiple Phase 1/2 gene-therapy trials move into registrational studies, alongside novel antioxidant approaches and AI-driven biomarkers. Today’s conversation cuts through the jargon to give you a clear picture of where the field stands—and where it’s headed.

Key Takeaways

• Beyond RPE65: While Luxturna paved the way, newer AAV-based therapies for X-linked RP (RPGR) and other targets are now in Phase 2 and Phase 3 trials, with early data showing promising safety and efficacy.

• Imaging & Function: Prof. Michaelides is pioneering next-generation retinal imaging devices and novel functional assays to capture meaningful changes in vision—critical for shortening trial timelines.

• Antioxidant Strategies: High-dose N-acetylcysteine trials are under way, offering a non-viral approach to slow photoreceptor degeneration across multiple genetic subtypes.

• AI in Stratification: Machine-learning algorithms on retinal scans can help predict progression rate and identify the best candidates for specific therapies, improving both trial design and patient outcomes.

• Balancing Dose & Safety: Finding the sweet spot between transgene expression and immune activation remains a core challenge—Prof. Michaelides shares lessons learned from dose-escalation cohorts.

• Phase 3 & Beyond: With over a hundred patients enrolled in pivotal studies, we’re closing in on potential approvals—but long-term follow-up and real-world evidence will determine ultimate impact.

About the Guest Prof. Michelle Michaelides is a clinician-scientist specializing in inherited retinal diseases. She leads dedicated adult and pediatric IRD clinics, oversees the development of advanced imaging and functional biomarkers, and serves as principal investigator on over ten clinical trials spanning gene therapies, antioxidant agents, and AI-guided stratification tools. Prof. Michaelides regularly lectures at international conferences and collaborates with industry and academic partners to accelerate the translation of research into real-world treatments.

In this latest episode of the BroadEye podcast, hosts Shawn Maloney and Dr. Bruno Fernandes sit down with Dr. Arshad M. Khanani, MD, MA, FASRS, a pioneer in vitreoretinal gene-therapy trials and Managing Partner at Sierra Eye Associates. Dr. Khanani shares front-line insights into how genetic medicines are reshaping treatment for inherited and degenerative retinal diseases, highlighting both the promise and the practical challenges of bringing one-time therapies to patients.

Why Gene Therapy Matters Today Recent years have seen the first US approvals of in-vivo retinal gene therapies, beginning with voretigene neparvovec (Luxturna) for RPE65-mediated inherited retinal dystrophy in December 2017. These one-off treatments offer durable vision improvements where none existed before, but they also raise questions of long-term safety, vector delivery, and equitable access.

Dr. Khanani’s Journey With over a decade leading surgical trials in sustained-delivery and viral-vector therapies, Dr. Khanani has overseen early human work on next-generation agents—including subretinal injections of AAV vectors and novel capsid designs. He describes lessons learned from Phase 1 safety studies through global registrational trials, emphasizing iterative “vector evolution” to boost efficacy and minimize inflammation.

Key Takeaways

• Vector Optimization: Directed-evolution platforms are accelerating discovery of capsids that target photoreceptors more precisely, reducing off-target toxicity.

• Durability vs. Dose: Striking the right balance between transgene expression and immune activation remains central—higher doses don’t always equal better outcomes.

• Regulatory Pathways: While Luxturna set a precedent, streamlined FDA and EMA guidance on trial endpoints and real-world evidence will shape the next wave of approvals.

• Cost & Access: Innovative payment models (e.g., outcomes-based installment plans) are emerging to address the multi-hundred-thousand-dollar price tags of these therapies.

About the Guest Dr. Arshad M. Khanani, MD, MA, FASRS, is a vitreoretinal surgeon, researcher, and Managing Partner at Sierra Eye Associates in Reno, Nevada. He holds dual degrees in medicine and medical humanities from the University of Nevada, Reno, and is a fellow of the American Society of Retina Specialists. Dr. Khanani has authored over 100 peer-reviewed articles on retinal disease and served as principal investigator on more than 30 clinical trials of gene and cell therapies for inherited and age-related retinal disorders. He also lectures internationally on surgical innovation, vector design, and the economics of advanced ocular treatments.