FECD-TRACE: Fuchs' Endothelial Corneal Dystrophy TRAjectory and Correlation With Genotype in the United Kingdom

NCT ID: NCT06881771

Last Updated: 2025-03-18

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-02-01
• Study Completion Date: 2027-02-01

Brief Summary

FECD-TRACE is an integral component of a large research program dedicated to Fuchs Endothelial Corneal Dystrophy (FECD) in the United Kingdom. This longitudinal, observational study aims to comprehensively characterize a cohort of younger research participants who have a genetic predisposition to developing FECD. By utilizing advanced anterior segment imaging techniques, the study will monitor these individuals over a span of several years, capturing phenotypic changes that reflect the progression of the disease. Concurrently, genetic biomarkers will be examined to establish correlations with the observed phenotypic changes. The primary objective of FECD-TRACE is to enhance our understanding of the intricate genetic mechanisms underlying FECD and establish connections between these genetic findings and clinical outcomes. Ultimately, this research strives to facilitate the development of personalized care approaches for individuals affected by FECD.

Detailed Description

FECD is the most prevalent repeat expansion disease in humans. Clinical anticipation and intergenerational expansion of disease-associated repeats are features of other repeat expansion diseases, but this area has not been comprehensively addressed in FECD. Due to its insidious onset and slow disease progression, early diagnosis of FECD in pre-symptomatic patients is challenging.

To gain insights into the variable penetrance of FECD and to identify early signs of the disease in genetically predisposed but asymptomatic individuals (i.e., a pre-symptomatic cohort), we aim to recruit biological relatives of FECD patients receiving care at study sites, as well as individuals with early-stage disease. By combining genotyping and clinical phenotyping, we seek to elucidate the underlying factors influencing disease manifestation.

Our deep phenotyping approach encompasses an array of advanced imaging techniques such as visual acuity assessment, contrast sensitivity evaluation, slit-lamp photography, specular microscopy, Scheimpflug tomography, and anterior segment optical coherence tomography. These cutting-edge modalities enable the detection of subclinical corneal edema by revealing subtle changes in corneal shape, volume, and reflectivity at a high resolution.

The imaging data obtained from participants will undergo meticulous quantitative analysis, allowing for the classification of anterior segment features and extraction of image-derived phenotypes. To capture the dynamic nature of FECD, eligible participants will be invited for follow-up examinations, facilitating a longitudinal assessment of disease progression.

Conditions

Fuchs Dystrophy; Fuchs' Endothelial Dystrophy; Fuchs' Endothelial Corneal Dystrophy of Bilateral Eyes; Corneal Dystrophy Fuchs; Corneal Dystrophy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Pre-symptomatic FECD cohort

1. Have at least one biological first-degree relative with a confirmed diagnosis of FECD AND have TCF4 gene CTG18.1 expansion ≥ 50 repeats OR

2. Confirmed diagnosis of FECD by a qualified ophthalmologist but does not have clinically evident corneal oedema

Clinical phenotyping

Intervention Type: DIAGNOSTIC_TEST

• Visual acuity assessment
• Contrast sensitivity evaluation
• Slit-lamp photography
• Specular microscopy
• Scheimpflug tomography
• Anterior segment optical coherence tomography
• In vivo confocal microscopy
• Spatio-temporal optical coherence tomography

CTG18.1 Expansion Status Genotyping

Intervention Type: GENETIC

Genotyping for trinucleotide repeat in the TCF4 gene (CTG18.1) and other genetic biomarkers using blood or saliva derived genomic DNA. This includes:

• Short tandem repeat - PCR
• Triplet-repeat primed - PCR
• Genome-wide single nucleotide polymorphism genotyping
• Ultra-deep locus-specific next-generation sequencing

Control cohort

1. Have no known family history nor clinical features of FECD OR

2. Have known family history of FECD but have been tested for the TCF4 gene CTG18.1 expansion and are not at genetic risk for FECD (CTG < 50 repeats).

Clinical phenotyping

Intervention Type: DIAGNOSTIC_TEST

• Visual acuity assessment
• Contrast sensitivity evaluation
• Slit-lamp photography
• Specular microscopy
• Scheimpflug tomography
• Anterior segment optical coherence tomography
• In vivo confocal microscopy
• Spatio-temporal optical coherence tomography

CTG18.1 Expansion Status Genotyping

Intervention Type: GENETIC

Genotyping for trinucleotide repeat in the TCF4 gene (CTG18.1) and other genetic biomarkers using blood or saliva derived genomic DNA. This includes:

• Short tandem repeat - PCR
• Triplet-repeat primed - PCR
• Genome-wide single nucleotide polymorphism genotyping
• Ultra-deep locus-specific next-generation sequencing

Interventions

Clinical phenotyping

• Visual acuity assessment
• Contrast sensitivity evaluation
• Slit-lamp photography
• Specular microscopy
• Scheimpflug tomography
• Anterior segment optical coherence tomography
• In vivo confocal microscopy
• Spatio-temporal optical coherence tomography

Intervention Type: DIAGNOSTIC_TEST

CTG18.1 Expansion Status Genotyping

Genotyping for trinucleotide repeat in the TCF4 gene (CTG18.1) and other genetic biomarkers using blood or saliva derived genomic DNA. This includes:

• Short tandem repeat - PCR
• Triplet-repeat primed - PCR
• Genome-wide single nucleotide polymorphism genotyping
• Ultra-deep locus-specific next-generation sequencing

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Willing and able to provide informed consent for participation in the study
• Willing to attend scheduled study visits and undergo a clinical examination
• Willing to donate blood/saliva samples
• Fulfil the abovementioned cohort criteria

Exclusion Criteria

• Presence of a secondary cause for corneal endothelial dysfunction or oedema
• Presence of clinically evident corneal oedema
• History of concurrent corneal diseases
• History of corneal surgeries, including corneal transplantation
• Cognitive impairment or inability to provide informed consent for participation in the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alice Davidson, PhD

Role: PRINCIPAL_INVESTIGATOR

University College, London

Locations

University College London

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Siyin Liu, MBChB

Role: CONTACT

siyin.liu@ucl.ac.uk

+44207 253 3411 ext. 4454

Facility Contacts

Siyin Liu

Role: primary

+4420 7608 6800

Other Identifiers

145682

Identifier Type: -

Identifier Source: org_study_id