PURPOSE: To formulate an Epithelial Modulation index to differentiate between eyes with contact lens warpage and keratoconus. METHODS: Normal eyes and eyes with either contact lens warpage or keratoconus were scanned by a Fourier-domain optical coherence tomography (OCT) system. Maps of epithelial thickness and anterior surface mean curvature were generated and converted to deviation maps by subtracting the average maps from a healthy population. The Epithelial Modulation index was defined as the covariance between the two types of deviation maps. A logistic regression model was used to classify eyes as non-keratoconus (normal or warp-age) or keratoconus (manifest, subclinical, or forme fruste). RESULTS: The average Epithelial Modulation index value for normal eyes was -0.6 ± 1.0 µm/m. Eyes with keratoconus were characterized by coincident high anterior surface mean curvature and low epithelial thickness, resulting in a high Epithelial Modulation index (manifest: 103.0 ± 82.9 µm/m, subclinical: 37.0 ± 23.0 µm/m, forme fruste: 7.3 ± 13.2 µm/m). The Epithelial Modulation index was closer to normal for eyes with warpage (-1.9 ± 4.0 µm/m). The classification accuracy of the Epithelial Modulation index during five-fold cross-validation of the logistic regression model was 100 ± 0% for normal eyes and 99.0 ± 2.0% for eyes with warpage. The accuracy was 100 ± 0%, 100 ± 0%, and 53.1 ± 1.5% for the manifest, subclinical, and forme fruste keratoconus groups, respectively. CONCLUSIONS: The Epithelial Modulation index is useful in distinguishing eyes with secondary epithelial modulation (keratoconus) from those with primary epithelial deformation (contact lens-related warpage). [J Refract Surg. 2022;38(2):112-119.].
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