Multi-luminance mobility testing after gene therapy in the context of retinal functional diagnostics

Area of Science:

• Ophthalmology
• Gene Therapy
• Retinal Degeneration

Background:

• Voretigene neparvovec (Luxturna®) is the first gene therapy approved for RPE65-linked Leber congenital amaurosis (LCA).
• While Luxturna shows variable individual effects, most patients report improved daily vision.
• Visual navigation tests are used in clinical trials, but their interpretation relative to conventional visual function parameters is unclear.

Purpose of the Study:

• To evaluate the utility of a multi-luminance visual navigation test (Ora-VNCTM) in assessing outcomes after Luxturna gene therapy for LCA.
• To correlate visual navigation test performance with changes in conventional visual function measures.

Main Methods:

• Seven LCA patients received Luxturna gene therapy.
• A multi-luminance visual navigation test (Ora-VNCTM) was administered before and 3 months post-therapy.
• Performance was assessed by the luminance level at which the course was passed and correlated with changes in visual acuity, full-field stimulus thresholds, chromatic pupil campimetry, and dark-adapted perimetry.

Main Results:

• Most participants showed improvement in the visual navigation task, regardless of changes in conventional visual function measures.
• Patients with advanced retinal degeneration showed no significant changes in conventional measures.
• Improvement in visual navigation correlated best with changes in full-field stimulus thresholds.

Conclusions:

• Improved visual navigation in some patients may be linked to rod reactivation.
• Performance in easier levels of the navigation test may be influenced by confounding factors in patients with low vision.
• Visual navigation tests may be most meaningful for patients with better-preserved visual functions.