Relationship of severity of Fuchs endothelial corneal dystrophy with triplet repeat expansion in TCF4 and The Potential Implications to Surgical Intervention

Abstract

Purpose : To determine whether the TCF4 CTG18.1 expansion influences the severity of Fuchs endothelial corneal dystrophy (FECD) and to correlate the presence of CTG18.1 triplet repeat expansions (≥50 repeats) with risk of keratoplasty and risk of corneal oedema following cataract surgery.

Methods : 286 patients were enrolled in a longitudinal study of FECD, defined as central guttae, seen on slit-lamp biomicroscopy, corneal oedema and/or keratoplasty for FECD in both eyes. CTG18.1 was genotyped using a short tandem repeat assay. Genotype status was correlated with previous keratoplasty and previous cataract surgery history. A positive expansion was defined as eaqual to or greater than 50 CTG repeats.

Results : 219 (76.6%) of 286 FECD patients investigated had at least one expanded copy (≥ 50 repeats) of the CTG18.1 allele. A higher proportion of individuals with an allele expansion had undergone keratoplasty (87.2%) compared with those without the expanded allele (79.1%). However, this finding was not statistically significant (p=0.39). We also observed that in 125 phakic FECD patients with no antecedent risk of cataract surgery, the relationship between repeat length and requirement of keratoplasty was not significant (p=0.89).

Conclusions : We present a genotype – phenotype correlation of expanded CTG 18.1 genotype status and surgical intervention in a UK FECD population. Results suggest that an expanded CTG18.1 repeat is not a major risk for severity of disease when defined as prevalence of keratoplasty. The study will guide our longitudinal study of a larger cohort.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.