Inter-zonal epithelial thickness differences for early keratoconus detection using optical coherence tomography

Purpose: To develop and test a parameter for early keratoconus screening by quantifying the localized epithelial thickness differences in keratoconic eyes. Methods: The cross-sectional study included 189 eyes of 116 subjects in total: 86 eyes of 54 keratoconus patients with bilateral ectasia and 40 eyes of 20 healthy subjects in the parameter-development dataset and 42 eyes of 21 keratoconus patients with asymmetric ectasia and 21 eyes of 21 healthy subjects in the parameter-validation dataset. Epithelial thickness maps were obtained using anterior segment optical coherence tomography and the inter-zonal epithelial thickness differences were calculated. The developed parameter was tested in keratoconus patients with asymmetric ectasia. Results: Compared to healthy controls, the inferior-temporal and global inter-zonal epithelial thickness differences were higher not only in eyes with tomographically significant keratoconus (median [interquartile range] of 4.42 [3.13] mu m vs. 0.78 [0.42] mu m, p < 0.001, and 3.05 [1.51] <mu>m vs. 1.07 [0.26] mu m, p < 0.001, respectively), but also in tomographically normal keratoconus fellow eyes (1.36 [0.85] <mu>m vs. 0.78 [0.42] mu m, p = 0.005, and 1.31 [0.32] mu m vs. 1.07 [0.26] mu m, p = 0.01, respectively). The inferior-temporal inter-zonal epithelial thickness differences had an area under the receiver operating characteristic curve (95% confidence interval) of 0.991 (0.972-1) for detecting tomographically significant keratoconus and 0.749 (0.598-0.901) for differentiating between tomographically normal keratoconus fellow eyes and healthy controls. Conclusions: The inter-zonal epithelial thickness differences are increased in keratoconus fellow eyes which still have a normal Scheimpflug corneal tomography, and therefore may serve as a useful parameter to detect early ectatic changes.