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.
