OBJECTIVE: To evaluate corneal sensitivity and corneal nerve morphology among patients with Wolfram syndrome (WFS).
METHODS: An observational clinical case series with confirmatory experiments.
METHODS: A group of 12 patients with biallelic mutations in the WFS1 gene and a control group composed of 30 individuals with type 1 diabetes (T1D).
METHODS: All subjects (n=42) underwent a complete ophthalmic examination, esthesiometry and retinal nerve fiber layer assessment using optical coherence tomography. Morphological assessment of corneal neuropathy by in vivo corneal confocal microscopy (IVCCM) was conducted in 11 patients with WFS (both eyes) and 1 WFS patient (one eye) as well as in 24 T1D patients (both eyes in 6 patients and one eye in 18 patients). Additionally, corneas from Wfs1KO mice and their wild-type (Wfs1WT) littermates were subjected to laser scanning confocal microscopy (LSCM).
RESULTS: Corneal sensitivity was significantly reduced in WFS patients compared to T1D patients (4.50 (3.50-5.50) cm vs. 6.00 (6.00-6.00) cm; p<10-5). Additionally, corneal nerve fiber and branch density as well as nerve fiber length were low among patients with WFS. Corneal sensitivity correlated with macular average thickness (R=0.6928, p=0.039) and BCVA (R=-0.61, p=0.002) in the WFS group. Similarly, Wfs1KO mice also presented corneal neurodegeneration changes when corneal nerve fiber density and length were measured using LSCM.
CONCLUSIONS: Reduced corneal sensitivity and corneal nerve degeneration are observed in WFS. Corneal sensitivity is linked with the degree of disease progression as measured by visual acuity and retinal thinning.