Ora visual navigation course™ mobility test results in two individuals with CEP290 LCA after intravitreal injection of antisense oligonucleotide

PURPOSE: This study aimed to report the longitudinal Ora Visual Navigation Course (Ora VNC™) mobility test results in two individuals, with CEP290 LCA following intravitreal injections of an antisense oligonucleotide, sepofarsen. METHODS: Two individuals were enrolled in the Illuminate Phase 3 trial and subsequently in the Post-Trial Access (PTA) program, undergoing Ora VNC™ across 12 visits. RESULTS: Subject 1 was initially randomized to the control (sham) group and switched to treatment from control group from the month 12 visit onwards. This individual passed only a few courses but demonstrated signs of enhanced spatial perception (defined by, among others, the ability to perceive objects' shapes and sizes). FST (full-field stimulus threshold) supported the light sensitivity gain in this subject. In contrast, subject 2, who received treatment since baseline visit, successfully completed mobility tests in all visits with progressive improvement, reaching lower luminance and more challenging contrast settings over time. According to the technicians' report, both subjects demonstrated an increase in perceived obstacle recognition during iterations, which may reflect improvement of mobility-based visual function outcomes. CONCLUSION: The Ora VNC™ mobility test captured mobility-based visual function gains, including subtle spatial improvements, but may lack sensitivity in individuals with extremely low vision, potentially overlooking small but patient-relevant changes.