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

University College London (UCL)

Status: Enrolling

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

Treatments: Genetic: CTG18.1 Expansion Status Genotyping; Diagnostic Test: Clinical phenotyping

Study type: Observational

Funder types: Other

Identifiers

NCT06881771

145682

Details and patient eligibility

About

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.

Full 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.

Enrollment: 500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

500 participants in 2 patient groups

Pre-symptomatic FECD cohort

Description:

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

Treatment:

Diagnostic Test: Clinical phenotyping

Genetic: CTG18.1 Expansion Status Genotyping

Control cohort

Description:

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).

Treatment:

Diagnostic Test: Clinical phenotyping

Genetic: CTG18.1 Expansion Status Genotyping