Open AccessTrinucleotide repeat expansion length as a predictor of the clinical progression of Fuchs’ Endothelial Corneal Dystrophy
Author(s) -
Yu Qiang Soh,
Gary Peh Swee Lim,
Hla Myint Htoon,
Xin Gong,
Venkateswara Mootha,
Eranga N. Vithana,
Viridiana Kocaba,
Jodhbir S. Mehta
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0210996
Subject(s) - trinucleotide repeat expansion , medicine , prospective cohort study , ophthalmology , allele , corneal endothelium , cohort , gastroenterology , cornea , biology , genetics , gene
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 >700μm, b) ECD decreased to <700 cells/mm 2 , 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.