Impact of TCF4 Repeat Number on Resolution of Corneal Edema after Descemet's Stripping Only in Fuchs Dystrophy: A Pilot Study.

Natasha Spiteri,Katherine Van Bysterveldt,Nino Hirnschall,Alec Lin Hou,Matthew Ball,Andrea L Vincent,Gregory Moloney

doi:10.3390/vision5040047

Abstract

Purpose: To investigate whether Fuchs endothelial corneal dystrophy (FECD) genotype, specifically transcription factor 4 (TCF4) CTG triplet repeat “load” predicts time to clearance following Descemet’s Stripping Only (DSO). Methods: This prospective, interventional trial was conducted on consecutive FECD patients undergoing DSO. Genetic analysis using patients’ saliva was performed to assess the extent of CTG expansion using short tandem repeat analysis, corroborated gel electrophoresis and Sanger sequencing. Polymerase chain reaction and bidirectional Sanger sequencing was undertaken. Partial least square regression and logistic regression modelling was used to evaluate the predictive power of TCF4 repeats on corneal clearance. Results: Of 11 eyes of 11 patients, 8 showed complete corneal clearance. For these 8 patients, mean TCF4 allele repeat was 24.8 (SD: 23.7, range: 11–63) and 63.4 (SD: 30.3; range: 11–97), respectively. In total, 9/11 (81.8%) had expanded CTG repeats (>40) in one allele. In cases with an allele repeat ≥80, there was a significantly increased risk of corneal non-clearance (odds ratio 18.2, p = 0.009). Conclusion: Whilst it was not possible to predict time to corneal clearance based on CTG repeats, there is a significant correlation between allele repeats and achievement of corneal clearance.

Highlights

Fuchs endothelial corneal dystrophy (FECD) with corneal decompensation is one of the commonest indications for corneal transplant surgery, but alternative surgical techniques are currently being explored, such as planned descemetorhexis without endothelial keratoplasty [1,2,3,4,5,6]
This study shows that a high repeat in transcription factor 4 (TCF4) is a significant risk factor for incomplete clearance after Descemet’s Stripping Only (DSO)
It was not possible to predict time to clearance in successful cases based on CTG triplet repeat load in the TCF4 gene

Summary

Introduction

Fuchs endothelial corneal dystrophy (FECD) with corneal decompensation is one of the commonest indications for corneal transplant surgery, but alternative surgical techniques are currently being explored, such as planned descemetorhexis (peeling the Descemet membrane) without endothelial keratoplasty [1,2,3,4,5,6]. This technique obviates the need for donor corneal tissue. Whether the transcription factor 4 (TCF4) CTG triplet repeat “load” would predict time to healing following Descemet’s Stripping Only (DSO)

Methods

Results

Conclusion