The aim of this study was to determine the detection of keratoconus using corneal biomechanical parameters only, a corneal tomographic parameter only, and a parameter that combines corneal biomechanical and tomographic indices. The discriminatory power of the Pentacam Random Forest Index (PRFI), Belin/Ambrósio Enhanced Ectasia Display (BAD-D) index, Corvis Biomechanical Index (CBI), and Tomographic and Biomechanical Index (TBI) to differentiate between normal eyes (n = 84), eyes with very asymmetric corneal ectasia (VAE-E, n = 21), and the fellow eyes without apparent ectasia based on normal tomography (VAE-NT, n = 21) was assessed. Statistical analyses were completed with R software using t-tests, Wilcoxon rank sum tests, and receiver operating characteristic (ROC) curves. The DeLong test was used to compare the area under the ROC curve (AUROC). The TBI and PRFI had the highest AUROC when distinguishing between normal and VAE-E corneas (AUROC = 1.00, 95% CI = 1.00-1.00); however, they were not statistically superior to the CBI (AUROC = 0.97, P = 0.27) or BAD-D (AUROC = 1.00, P = 0.34). The TBI (AUROC = 0.92, 95% CI = 0.86-0.98) was superior to CBI (AUROC = 0.78, P = 0.02) and BAD-D (AUROC = 0.81, P = 0.02) when distinguishing between healthy and VAE-NT corneas. At a threshold of 0.72, the TBI had 99% sensitivity, 67% specificity, and 92% accuracy in distinguishing normal and VAE-NT corneas. The TBI is a useful parameter for the screening of subclinical and frank keratoconus in tomographically normal eyes.