Q&A: Stephen Tsang discusses outcomes in retinitis pigmentosa and Stargardt trials

Stephen Tsang, MD, PhD, professor at Columbia University and attending physician at NewYork-Presbyterian Hospital, shared encouraging early findings on the use of optogenetic therapy for patients with retinitis pigmentosa and Stargardt disease at the 2025 annual meeting of the American Academy of Ophthalmology (AAO). This meeting was held from October 18-20, 2025 in Orlando, Florida, United States.

According to Tsang, a single optogenetic treatment has led to measurable improvements in vision for patients affected by these inherited retinal diseases. In patients with retinitis pigmentosa, vision gains averaged about 15 letters on an eye chart. For those with Stargardt disease, improvements reached nine letters without an amplifier and up to 13 letters when used in combination with amplification glasses. Tsang emphasized the broad potential of optogenetics, noting that the approach could benefit patients regardless of their specific genetic mutation.

Note: The following conversation has been lightly edited for clarity.

Ophthalmology Times Europe: What efficacy outcomes have been observed with optogenetic therapy in adults with retinitis pigmentosa and Stargardt disease, and how do these compare to baseline visual function?

Stephen Tsang, MD, PhD: So [patients with] Stargardt, and also for retinitis pigmentosa, many of them eventually need a cane or a dog for mobility. With optogenetic therapy, [after] a single treatment, patients with retinitis pigmentosa can increase by almost about five letters on the chart. And then for Stargardt patients without an amplifier, glasses, patients can get about nine letters' improvement. With an amplifier, patient are able to get about 13 letters of improvement. In both cases, patients improve both mobility and object recognition.

OTE: What safety considerations and adverse events have been reported, and how might these influence patient selection and clinical implementation?

Tsang: Most of the time for optogenetics, Phase 1/2 trial is mostly looking for safety, and there's no really serious adverse event that's not controllable by steroids, and very typical for any kind of intravitreal gene therapy.

OTE: How do the results of these trials inform future directions for optogenetic therapies in inherited retinal diseases, including potential combination or adjunctive treatments?

Tsang: These early results are encouraging to go forward to a Phase 3 trial, to a larger number of patients, because optogenetics can also cover independent of what the patient's mutations [are]. There are more than 80 different genes that can cause retinitis pigmentosa, and in principle, they can be all covered by the optogenetics approach. In Stargardt, also, there's more than 500 different mutations in the gene encoding Stargardt, so the precision base-pair treatment, or CRISPR therapeutics, may be not so practical for Stargardt patients. These are the early stage of optogenetics treatment and some of the newer generation in the pipeline would even achieve much higher resolution.