Trinucleotide Repeat Expansion Length as a Predictor of the Clinical Progression of Fuchs Endothelial Corneal Dystrophy

Abstract

Purpose : To determine if CTG18.1 TNR expansion length prognosticates the clinical progression of Fuchs Endothelial Corneal Dystrophy (FECD).

Methods : This was a prospective cohort study. A total of 51 patients with newly diagnosed FECD were recruited and followed-up over a period of 12 years, from November 2004 to April 2016. Baseline clinical measurements included central corneal thickness (CCT), endothelial cell density (ECD) and CTG18.1 TNR expansion length from peripheral leukocytes, with yearly repeat measurements of CCT and ECD. A patient was defined to have experienced significant clinical progression and to have developed Threshold Disease if any of these criteria were fulfilled in either eye: a) CCT increased to >700mm, b) ECD decreased to <700 cells/mm², or c) underwent keratoplasty for treatment of FECD.

Results : Patients were categorized as having at least one allele whose maximum allele length was equal to or greater than 40 repeats (L≥40, n = 22, 43.1%), or having both alleles shorter than 40 repeats (L<40). Threshold Disease rates at the 5-year time point were 87.5% for the L≥40 group and 47.8% for the L<40 group (p = 0.012). This difference narrowed and was no longer statistically significant at the 8-years (92.9% vs 78.9%, p = 0.278) and 10-years (92.9% vs 84.2%, p = 0.426) time points.

Conclusions : L≥40 patients are at greater risk of FECD progression and development of Threshold Disease within the first 5 years following diagnosis. In this study, we found CTG repeat length to be a useful adjunct indicator which may be used to counsel an FECD patient regarding his or her risk of significant clinical progression and keratoplasty over the next 10 years.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.