Nanopore sequencing method for CTG18.1 expansion in TCF4 in late-onset Fuchs endothelial corneal dystrophy and a comparison of the structural features of cornea with first-degree relatives

Background To evaluate the relationship between the number of trinucleotide repeats (TNR) in late-onset Fuchs corneal endothelial dystrophy (FCED) and to compare the endothelial properties of FCED, first-degree relatives, and controls. Methods Blood samples were collected from FCEDs to determine TNR number. The FCED patients, first-degree relatives, and controls were examined with specular microscopy for central corneal thickness (CCT), endothelial cell density (ECD), pleomorphism and polymegatism, and with corneal topography for specific indicators such as (i) displacement of thinnest point of cornea, (ii) loss of isopachs, (iii) focal posterior surface depression towards anterior chamber. Results This study included 92 patients with FCED, 92 first-degree relatives, and 96 controls. CCT was thickest in FCEDs (558.0 μm) ( p < 0.05) while there was no difference between relatives (533.0 μm) and controls (530.4 μm) ( p = 0.845). ECD was decreased in both FCED (2069.2 mm 2 ) and relatives (2171.4 mm 2 ) than controls (2822.9 mm 2 ) ( p < 0.05 in both). The presence of pleomorphism and polymegatism was significant in patients with FCED (93.4% and 93.4%, respectively), relatives (86.9% and 86.04%, respectively), and controls (8.33% and 1.04%, respectively) ( p < 0.05). Specific topographic indicators differed among the groups ( p < 0.05). The mean repeat number of the FCED patients was 17.48 ± 4.54 (12–25) times. The TNR number of FCED cases correlated with the relative CCT ( p < 0.05, R = 0.615) and cell density ( p = 0.009, R = -0.499). Conclusions A strong association between the corneal endothelium in relatives and TNR number of FCEDs was defined. Relatives tended to have fewer corneal endothelial cells, even though they did not have clinical findings.