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

Recruiting

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

• Registration Number: NCT06881771
• Lead Sponsor: University College, London

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.

Study Timeline

• Study Start: 2024-02-01
• Study First Submitted: 2025-02-28
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-11
• Last Update Submitted: 2025-03-11
• Study First Posted: 2025-03-18
• Last Update Posted: 2025-03-18
• Primary Completion: 2026-02-01
• Study Completion: 2027-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Endothelial cell density measurement (cells/mm2)	Baseline	Specular Microscopy - Endothelial cell density.
Detection of guttata (cells/mm2)	Baseline	In Vivo Confocal Microscopy (IVCM) - Detection of guttata
Corneal thickness (in micrometers)	Baseline	Anterior Segment Optical Coherence Tomography (AS-OCT) - Corneal thickness
CTG18.1 allele length (in number)	Baseline	Polymerase Chain Reaction (PCR) will be performed from DNA (blood sample)
Documentation of early corneal guttata development (Binary)	Baseline	Slit-Lamp Photography - Documentation of early corneal guttata development.
Best-corrected visual acuity in LogMAR scale	Baseline	Visual acuity measured by LogMAR chart
Corneal nerve density (nerves/mm2)	Baseline	In Vivo Confocal Microscopy (IVCM) - Detection of nerves

Trial Locations

Locations (1)

University College London; 🇬🇧 London, United Kingdom