Abstract
Purpose :
ADOA is the most common inherited optic nerve disorder. It is a rare disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Roughly half of people with ADOA fail driving standards and up to 46% are registered as legally blind. An estimated 65% to 90% of cases are caused by mutations in the OPA1 gene, most of which lead to haploinsufficiency resulting in 50% OPA1 protein expression and disease manifestation. OPA1 is a dynamin-related GTPase that localizes to the mitochondrial inner membrane and reduced levels precipitate the loss of retinal ganglion cells secondary to mitochondrial dysfunction. Currently, there is no approved treatment for people living with ADOA. There are limited prospective data on the natural history of ADOA and mitochondrial dysfunction has not been studied in vivo. In the presence of retinal oxidative stress mitochondrial flavoproteins, when stimulated by blue light, display increased fluorescence measured as green light. Ocumet Beacon leverages this by quantitating this light emission, generating a retinal flavoprotein fluorescence (FPF) score. FPF functions as a biomarker of mitochondrial dysfunction in vivo. Here we present initial baseline data from FALCON from a patient subset who completed the Beacon assessment.
Methods :
FALCON is a multicenter, prospective natural history study of people ages 8 to 60 who have an established clinical diagnosis of ADOA that is caused by a heterozygous OPA1 gene variant. No investigational medications or other treatments will be provided. The study enrolled 48 patients across 10 sites in the U.S., U.K., Italy, and Denmark. Patients undergo assessments at baseline, 6 months, 12 months, 18 months, and 24 months. There will be no additional follow-up period.
Results :
Nineteen patients (8 (8-17 years), 6 (18-40 years), and 5 (41-60 years)) completed baseline Beacon evaluation. For the subset of 19 patients, the mean duration since ADOA onset was 16.0 years (SD 13.71) with the mean (SD) LogMAR (25%) of 0.7 (0.37); and average reading speed of 96.4 (38.39) words per minute. FPF is being analyzed and will be reported at presentation time.
Conclusions :
FPF may add to current diagnostic tools for earlier detection of ADOA mitochondrial dysfunction and may help to inform future studies as a measure of treatment response.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.