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

Официальное название

Investigating Genetic Causes and Molecular Mechanisms Responsible for Inherited Corneal Disease

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест 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
• Генная терапия 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

Первичные конечные точки

• Endothelial cell density measurement (cells/mm2) [Срок оценки: Baseline]
• CTG18.1 allele length (in number) [Срок оценки: Baseline]
• Detection of guttata (cells/mm2) [Срок оценки: Baseline]
• Corneal thickness (in micrometers) [Срок оценки: Baseline]
• Documentation of early corneal guttata development (Binary) [Срок оценки: Baseline]
• Best-corrected visual acuity in LogMAR scale [Срок оценки: Baseline]
• Corneal nerve density (nerves/mm2) [Срок оценки: Baseline]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Великобритания · 1 центр

• University College London — London

Идентификаторы

NCT: NCT06881771 · 145682

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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