Association between clinical phenotypes and TCF4 repeat expansion in Fuchs endothelial corneal dystrophy

Abstract

Purpose : CTG trinucleotide repeat expansion in the third intron of TCF4 gene has been reported in patients with Fuchs endothelial corneal dystrophy (FECD). Here, we report a multimodal investigation on clinical phenotypes associated with the repeat expansion in TCF4.

Methods : One-hundred fifty eyes of 75 consecutive FECD patients (20 males, 55 females; average age 66.8±13.0 years) in Osaka University hospital were enrolled. Modified Krachmer grading scale was grade 1 in 7 eyes, 2 in 32 eyes, 3 in 28 eyes, 4 in 51 eyes, 5 in 6 eyes, 6 in 18 eyes. Eight eyes had a history of keratoplasty. CTG repeat expansion of leukocyte-derived genomic DNA was analyzed using fragment analysis by PCR and triplet repeat primed PCR. Ophthalmic examinations by Scheimpflug tomography (Pentacam HR, Oculus) and anterior segment coherence tomography (AS-OCT) (CASIA2, TOMEY) were applied. Corneal densitometry and anterior segment morphology indices were compared between FECD patients with CTG trinucleotide repeat expansion (expansion group) and those without expansion (non-expansion group).

Results : Sixteen of 75 FECD patients (21%) had repeat expansion of 50 or more. There were no differences between expansion and non-expansion group in demographic features including age, female ratio, modified Krachmer severity, and a history of keratoplasty (P>0.05 for all). Posterior and total corneal densitometry values of the central 0-2mm were significantly higher in expansion group than non-expansion group (13.36±3.79vs11.73±4.02, P=0.03)(21.73±5.85vs19.83±7.37, P=0.03). However, there was no difference in these values between the two groups with multivariate mixed model (P=0.56, 0.87, respectively). There were no significant differences in corneal densitometry values of other corneal segments between the two groups. Repeat expansion did not also affect anterior segment morphology detected by AS-OCT in FECD patients (p>0.05 for all), except for corneal thickness (P=0.02).

Conclusions : There was no difference in corneal back scattering between FECD patients with repeat expansion in TCF4 gene and those without repeat expansion. Corneal thickness was significantly higher in patients with repeat expansion.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.