A Longitudinal Natural History Study of OPA1-Associated Autosomal-Dominant Optic Atrophy (OPA-LONG)

Clinical Characterisation of OPA1-Associated Autosomal-Dominant Optic Atrophy

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.

Study Overview

• Status: Recruiting
• Conditions: Optic Atrophy, Autosomal Dominant; OPA1 Gene Mutation

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Sarah Marxsen; Phone Number: +49 89 4400 53770; Email: sarah.marxsen@med.uni-muenchen.de
• Study Contact Backup: Name: Ursula Reinstein, Dr. med. vet.; Email: ursula.reinstein@med.uni-muenchen.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80336
      • Recruiting
      • Department of Ophthalmology, LMU University Hospital, LMU Medizin, Ludwig-Maximilians-Universität München
      • Contact: Sarah Marxsen; Phone Number: +49-89-4400-53770; Email: sarah.marxsen@med.uni-muenchen.de
      • Sub-Investigator: Claudia Priglinger, Prof. Dr. med.
      • Sub-Investigator: Günther Rudolph, Prof. Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria:

• 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

(Participants are eligible for inclusion if all of the criteria mentioned above are met)

Exclusion Criteria:

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in retinal flavoprotein fluorescence intensity measured by flavoprotein fluorescence imaging	Change from baseline in retinal autofluorescence intensity measured using the OcuMet Beacon confocal scanning ophthalmoscope. The unit of measure is a device-specific autofluorescence intensity score.	Baseline and follow-up visits up to 3 years
Change in central visual field sensitivity measured by Humphrey 10-2 automated perimetry	Change from baseline in central visual field sensitivity measured using Humphrey 10-2 automated perimetry. The unit of measure is decibels.	Baseline and follow-up visits up to 3 years
Change in protan and tritan colour contrast thresholds measured by the Arden Colour Contrast Test	Change from baseline in protan and tritan colour contrast thresholds measured using the Arden Colour Contrast Test. Protan and tritan thresholds will be reported separately. The unit of measure is percent contrast.	Baseline and follow-up visits up to 3 years
Change in best-corrected visual acuity (BCVA) measured with high-contrast visual acuity testing	Change from baseline in best-corrected visual acuity (BCVA) measured using standardized high-contrast visual acuity testing. BCVA will be recorded as the number of letters correctly read or converted to logMAR for analysis. The unit of measure is logMAR or number of letters correctly read.	Baseline and follow-up visits up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pupil diameter measured by video-oculography using BulbiCAM	Change from baseline in pupil diameter measured by video-oculography using the BulbiCAM Pupil Dynamics test. The unit of measure is millimeters.	Baseline and follow-up visits up to 3 years
Change in pupillary peak velocity measured by video-oculography using BulbiCAM	Change from baseline in pupillary peak constriction and dilation velocity measured by video-oculography using the BulbiCAM Pupil Dynamics test. Constriction and dilation velocity will be reported separately. The unit of measure is millimeters per second.	Baseline and follow-up visits up to 3 years
Change in cumulative fixation time measured by BulbiCAM Fixation test	Change from baseline in the cumulative fixation time measured using the BulbiCAM. The unit of measure is seconds.	Baseline and follow-up visits up to 3 years
Change in smooth pursuit gain measured by video-oculography using BulbiCAM	Change from baseline in device-derived smooth pursuit gain measured during the BulbiCAM Smooth Pursuit test. The unit of measure is percent.	Baseline and follow-up visits up to 3 years
Change in objective central visual field sensitivity measured by KONAN ObjectiveFIELD Analyzer	Change from baseline in objective central visual field sensitivity measured using the KONAN ObjectiveFIELD Analyzer with multifocal pupillographic objective perimetry. The unit of measure is decibels.	Baseline and follow-up visits up to 3 years

Collaborators and Investigators

• Sponsor: Ludwig-Maximilians - University of Munich
• Investigators: Principal Investigator: Maximilian-Joachim Gerhardt, Dr. med., Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians-Universität München

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): November 1, 2030

Study Registration Dates

• First Submitted: June 21, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 28, 2026

Study Record Updates

• Last Update Posted (Actual): July 28, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Eye Diseases; Neurodegenerative Diseases; Eye Diseases, Hereditary; Heredodegenerative Disorders, Nervous System; Optic Nerve Diseases; Cranial Nerve Diseases; Mitochondrial Diseases; Optic Atrophies, Hereditary; Optic Atrophy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Optic Atrophy, Autosomal Dominant
• Other Study ID Numbers: 25-0268

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No