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Sanjay V Patel, Katrin Wacker, Ross Aleff, Eric Wieben, Keith Baratz; Trinucleotide repeat expansion in the TCF4 gene and corneal ultrastructural changes in Fuchs endothelial corneal dystrophy.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5665.
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© ARVO (1962-2015); The Authors (2016-present)
Fuchs endothelial corneal dystrophy (FECD) is associated with an intronic CTG trinucleotide repeat (TNR) expansion in the transcription factor 4 (TCF4) gene. In this study, we examined the relationship between TNR expansion and ultrastructural changes that result in increased backscattered light from corneas with FECD.
Anterior corneal backscatter was measured from Scheimpflug images using a standardized method that accounted for any variations in incident light intensity and sensitivity of the detecting camera. Central corneal thickness was measured by ultrasonic pachymetry. Mean TNR length of the longer allele was determined via short-tandem repeat assay, and extreme repeat lengths were verified by genomic Southern blots from leukocyte-derived DNA. Age at endothelial keratoplasty was recorded if patients underwent surgical treatment. An age standardization technique was applied to assess the associations between TNR length and corneal backscatter and thickness at the same age. Linear regression models were used to assess the association between TNR length and age at keratoplasty. Data from subjects without TNR expansion (<40 TNRs) were not included for analysis.
Forty-six female and 23 male participants were included of which 72 eyes of 41 participants underwent endothelial keratoplasty. Median TNR length was 79 (interquartile range, 23); 84% of subjects had allele expansion (>40 TNRs) with one subject having >2000 repeats. Among those with 40-200 TNRs, and with age standardization, increased TNR length was associated with increased anterior corneal backscatter (142 scatter units per 10 TNRs; 95%CI, 74–201; p<0.001) and thicker corneas (24 µm per 10 TNRs; 95%CI, 6–43; p=0.012). Increased TNR length was associated with younger age at endothelial keratoplasty (–1.9 years per 10 TNRs; 95% CI, –3.0 to –0.6 years; p=0.003; n=66).
The length of the TCF4 TNR in FECD is associated with more severe corneal ultrastructural changes, and with endothelial keratoplasty at a younger age. TNR length might aid clinicians with long-term prognostication of FECD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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