Study of BEST1 Vitelliform Macular Dystrophy

Natural History Study in Retinitis Pigmentosa Caused by Mutations in the BEST1 Gene

The purpose of this study is to establish the natural history of of participants with BESTROPHIN 1 Vitelliform Macular Dystrophy.

The blinding disorder Best Vitelliform Macular Dystrophy (VMD) is caused by any one of more than 250 different mutations in the BEST1 gene.

As new treatments are developed, a clear understanding of the natural history of disease progression of BEST1 VMD is necessary. The goals of this natural history study are to:

1. Report the natural history of retinal degeneration in participants with a clinical diagnosis of VMD with molecular confirmation of a pathogenic BEST1 mutation(s).
2. Identify sensitive structural and functional outcome measures to use for future multicenter clinical trials for the treatment of BESTROPHIN 1 VMD.
3. Compare progression of the identified structural and functional measures between the two eyes to judge the suitability of the second untreated eye as a control for a future clinical trial involving unilateral treatment
4. Identify well-defined patient populations for future clinical trials of investigative treatments for BEST1 VMD.

Study Overview

• Status: Recruiting
• Conditions: Retinitis Pigmentosa; Best Vitelliform Macular Dystrophy
• Intervention / Treatment: Other: Natural History Study

• Study Type: Observational
• Enrollment (Estimated): 52

Contacts and Locations

• Study Contact: Name: Stephen H Tsang, MD, PhD; Phone Number: 212-342-1186; Email: sht2@cumc.columbia.edu

Study Locations

• France
  • Paris, France
    • Not yet recruiting
    • Institut de la Vision/Centre de maladies rares du Centre Hospitalier National Ophtalmologique des Quinze-Vingts
    • Contact: Isabelle Audo, MD, PhD; Phone Number: +33 1 40 02 14 30; Email: isabelle.audo@inserm.fr
    • Contact: Camille Andrieu, MD; Phone Number: +33 1 40 02 14 51; Email: candrieu@15-20.fr
    • Principal Investigator: Isabelle Audo, MD, PhD
• Germany
  • Tuebingen, Germany
    • Recruiting
    • Eberhard Karls University Tubingen
    • Contact: Laura Kuehlewein, MD; Phone Number: +49 07071 29-88088; Email: laura.kuehlewein@med.uni-tuebingen.de
    • Contact: Katarina Stingl, MD; Phone Number: +49 7071 29 87421; Email: katarina.stingl@med.uni-tuebingen.de
    • Principal Investigator: Eberhart Zrenner, MD
• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Stephen H Tsang, MD, PhD; Phone Number: 212-342-1186; Email: sht2@columbia.edu

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients are expected to present to the clinic at all age groups; enrollment of subjects <18 years of age will be obtained by informed consent in the company of a parent or legal guardian. There will also be no gender-or ethnic/racial specific inclusion criteria. The enrollment of non-English speaking subjects is not expected.

Description

Inclusion Criteria:

• Ability to provide informed consent
• Diagnosis of BEST1-associated VMD by study physician, who are trained retinal specialists in the university clinic Must be able to commit to 4 follow-up study visits (3 years)

Exclusion Criteria:

• Systemic condition that prevents the participant from undergoing the exams

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Best Vitelliform Macular Dystrophy (VMD) Participants; Participants with a clinical picture of Retinitis pigmentosa with dominant and recessive variants in the BEST1 gene	Other: Natural History Study; Longitudinal assessment of participants with BEST1 Vitelliform Macular Dystrophy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medmont Dark Adapted Chromatic (DAC) Automated Perimeter		Up to 3 years
Full-field electroretinogram (ERG)	ERG conducted under International Society for Clinical Electrophysiology of Vision (ISCEV) Protocol.	Up to 3 years
Electroocoulogram (EOG)	EOG conducted under International Society for Clinical Electrophysiology of Vision (ISCEV) Protocol	Up to 3 years
Optical Coherence Tomography (OCT)		Up to 3 years
Fundus Autofluorescence (FAF)		Up to 3 years
Near-infrared fundus autofluorescence (NIR-AF)		Up to 3 years
Quantitative Fundus Autofluorescence (qAF)		Up to 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Best-corrected Visual Acuity (BCVA)	Up to 3 years
Color Fundus Photos	Up to 3 years
Macular Integrity Assessment (MAIA) Microperimetry	Up to 3 years
Goldman Kinetic Visual Field	Up to 3 years
Light-adapted Static Perimetry	Up to 3 years
Dark-adapted Chromatic Perimetry	Up to 3 years
Full-field Stimulus Testing	Up to 3 years

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Eye Institute (NEI); Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts; Universität Tübingen
• Investigators: Principal Investigator: Stephen H Tsang, MD, PhD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): April 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Retinal Degeneration; Retinitis; Retinitis Pigmentosa; Macular Degeneration; Vitelliform Macular Dystrophy
• Other Study ID Numbers: AAAT5994; R24EY028758 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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