A Longitudinal Natural History Study of OPA1-Associated Autosomal-Dominant Optic Atrophy

NCT07729982 | Recruiting

• 1 other identifier: 25-0268
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, monocenter, non-interventional observational study investigates the natural history as well as the clinical and genetic spectrum of OPA1-associated autosomal dominant optic atrophy. Participants will undergo standardized ophthalmic and functional assessments, including visual acuity testing, visual field testing, color vision and contrast sensitivity testing, optical coherence tomography, retinal flavoprotein fluorescence imaging, and video-oculography-based ocular motor and pupillary measurements. The study aims to characterize disease severity and progression over time and to identify structural, metabolic, and functional biomarkers that may serve as clinical endpoints for future therapeutic studies.

Conditions

OPA1 Gene Mutation; Optic Atrophy, Autosomal Dominant

Outcome Measures

Primary Outcomes (4)

• Change in 2.5% low-contrast visual acuity measured with Sloan letter charts

  Change from baseline in low-contrast visual acuity measured using 2.5% low-contrast Sloan letter charts. Low-contrast visual acuity will be recorded as the number of Sloan letters correctly read and may be converted to logMAR for analysis. The unit of measure is number of Sloan letters correctly read.

  Baseline and follow-up visits up to 3 years

• Change in contrast sensitivity

  Change from baseline in contrast sensitivity measured using the Manifold® Platform from Adaptive Sensory Technology. The unit of measure is log contrast sensitivity.

  Baseline and follow-up visits up to 3 years

• Change in macular ganglion cell layer thickness measured by optical coherence tomography

  Change from baseline in macular ganglion cell layer thickness, or ganglion cell-inner plexiform layer thickness where applicable, measured by optical coherence tomography. The unit of measure is micrometers.

  Baseline and follow-up visits up to 3 years

• Change in peripapillary retinal nerve fiber layer thickness measured by optical coherence tomography

  Change from baseline in peripapillary retinal nerve fiber layer thickness measured by optical coherence tomography. The unit of measure is micrometers.

  Baseline and follow-up visits up to 3 years

Secondary Outcomes (4)

• Change in retinal flavoprotein fluorescence intensity measured by flavoprotein fluorescence imaging

  Baseline and follow-up visits up to 3 years

• Change in central visual field sensitivity measured by Humphrey 10-2 automated perimetry

  Baseline and follow-up visits up to 3 years

• Change in protan and tritan colour contrast thresholds measured by the Arden Colour Contrast Test

  Baseline and follow-up visits up to 3 years

• Change in best-corrected visual acuity (BCVA) measured with high-contrast visual acuity testing

  Baseline and follow-up visits up to 3 years

Other Outcomes (5)

• Change in pupil diameter measured by video-oculography using BulbiCAM

  Baseline and follow-up visits up to 3 years

• Change in pupillary peak velocity measured by video-oculography using BulbiCAM

  Baseline and follow-up visits up to 3 years

• Change in cumulative fixation time measured by BulbiCAM Fixation test

  Baseline and follow-up visits up to 3 years

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the inherited retinal disease and ophthalmogenetics clinic of the Department of Ophthalmology, University Hospital, Ludwig-Maximilians-Universität München, Germany. The study population consists of patients followed at this tertiary referral center. Additional participants may be referred by genetic diagnostic centers or other physicians in Germany or abroad after molecular genetic testing and clinical suspicion of OPA1-related disease. Self-referral by patients with a previous diagnosis of OPA1-associated autosomal dominant optic atrophy is also accepted.

You may qualify if:

• Age 6 years or older
• Clinical diagnosis or clinical features consistent with optic atrophy
• Molecular genetic confirmation of a pathogenic or likely pathogenic variant in the OPA1 gene
• Ability of the participant, or the participant's parent or legal guardian, to understand the nature of the study and provide written informed consent

You may not qualify if:

• \- Severe systemic disease or medical condition that, in the opinion of the investigator, would preclude participation in the study-related examinations

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (1)

Department of Ophthalmology, LMU University Hospital, LMU Medizin, Ludwig-Maximilians-Universität München

Munich, Bavaria, 80336, Germany

RECRUITING

MeSH Terms

Conditions

Optic Atrophy, Autosomal Dominant

Condition Hierarchy (Ancestors)

Optic Atrophies, Hereditary; Optic Atrophy; Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Eye Diseases, Hereditary; Eye Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Maximilian-Joachim Gerhardt, Dr. med.

  Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians-Universität München

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Marxsen

CONTACT

+49 89 4400 53770; sarah.marxsen@med.uni-muenchen.de

Ursula Reinstein, Dr. med. vet.

CONTACT

ursula.reinstein@med.uni-muenchen.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. med.

Study Record Dates

• First Submitted: June 21, 2026
• First Posted: July 28, 2026
• Study Start: July 16, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): November 1, 2030
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)