ASRS 2025: 24-Month results of the phase 2 SKYLINE trial

Robert A. Sisk, MD, FACS, FASRS, from Cincinnati Eye Institute spoke with Opthalmology Times at the 2025 ASRS annual meeting, held in Long Beach California. He discussed the SKYLINE phase 2 trial investigating laruzova, a full-length RPGR gene therapy for X-linked retinitis pigmentosa.

The study aimed to evaluate the dose-dependent response and potential visual improvements in patients with this genetic condition. The trial focused on males aged 8 to 50 with a pathogenic RPGR gene variant. Participant selection criteria included measurable microperimetry sensitivity and an intact foveal ellipsoid band, which indicates the health of photoreceptor cells in the central retina.

Key findings revealed a significant improvement in microperimetry response in the high-dose group compared to the low-dose group. The research highlighted the importance of the ellipsoid zone in gene therapy, with patients having near-normal retinal anatomy more likely to benefit from the treatment.

The phase 3 trial (VISTA) is already fully recruited, with two primary endpoints: microperimetry and low luminance visual acuity. Dr. Sisk emphasized the challenges of identifying the optimal treatment window. Patients must have some vision decline (between 20/32 and 20/200) to show potential improvement, but not so much that the ellipsoid band is completely lost.

Looking forward, Sisk expressed optimism about expanding treatment options. He hopes that if the phase 3 study is approved, patients could be treated at earlier stages of the disease. Moreover, he anticipates a future with diverse therapeutic approaches, including:

1. Gene augmentation therapy
2. Gene-agnostic approaches
3. Stem cell studies
4. Optogenetic gene therapy for late-stage disease

The ultimate goal is to develop comprehensive treatment strategies that can provide more complete outcomes for patients with X-linked retinitis pigmentosa. Sisk believes that combining various therapeutic methods will offer the most promising approach to managing this genetic condition.