AAO 2023: Retina Subspecialty Day – “What’s New in Wet AMD”

Prashant Tailor, MD
Mayo Clinic, Rochester, MN

In his talk titled “What’s Next in Wet AMD,” Dr. Peter Kaiser delved into the latest advancements and future directions in the treatment of wet Age-related Macular Degeneration (AMD). Dr. Kaiser began by acknowledging the current landscape of wet AMD treatments, which includes agents targeting VEGF-A and placental growth factors. He highlighted that we’re entering an era dominated by biosimilars, with bevacizumab being specifically tailored for ophthalmological use.

A critical challenge in AMD treatment is decreasing the treatment burden on patients. Dr. Kaiser discussed strategies such as increasing medication doses to extend their half-life. He provided the example of high-dose aflibercept, which can be administered at six-month intervals, thereby reducing the frequency of treatments.

Dr. Kaiser touched upon a crucial point about the body’s response to treatments that block VEGF-A—it compensates by upregulating VEGF-C. He suggested that a pan-VEGF blockade, which would include VEGF-C, could potentially yield better outcomes. In this context, he mentioned some new therapies as being superior (OPT-302), likely due to its broader mechanism of action with VEGF-C and D blockage.

Gene therapy is also on the frontier of wet AMD treatment. Dr. Kaiser referred to RGX-314, which is currently in phase 3 trials involving subretinal delivery. This therapy aims to introduce genetic material to help the body produce its own AMD medication.

New pathways are being explored, such as tyrosine kinase inhibitors (TKIs), which have shown promise in treating wet AMD. Although TKIs have been utilized in oncology, their advent into ophthalmology is relatively new. Dr. Kaiser was optimistic about polymers of TKIs used in treatment-naive patients. He noted several studies detailing improvements in visual acuity and optical coherence tomography findings. When compared to Eylea, a TKI showed similar efficacy, with another TKI demonstrating similar results with 53% of patients being treatment-free.

Lastly, Dr. Kaiser discussed senescent cells, which contribute to the production of growth factors involved in AMD. By targeting these cells, there is potential to not only halt disease progression but also to regenerate function. He touched on UBX1325 which works as a potent Bcl-xl inhibitor as a drug that is currently undergoing clinical trials with some promise.

In summary, Dr. Kaiser’s talk presented an optimistic view of the future of wet AMD treatment, with a focus on extending treatment intervals, exploring new therapeutic targets like pan-VEGF blockers and TKIs, and innovative approaches such as gene therapy and senescent cell targeting. This approach aims to decrease patient burden while maintaining, if not improving, the efficacy of treatments.