Discriminant Value of Custom Ocular Response Analyzer Waveform Derivatives in Keratoconus

Purpose: To evaluate the performance of corneal hysteresis (CH), corneal resistance factor, and 16 investigator-derived Ocular Response Analyzer (ORA) variables in distinguishing keratoconus (KC) from the nondiseased state. Design: Retrospective case series. Participants: Fifty-four eyes of 27 unaffected patients and 49 eyes of 25 KC patients from the Instituto de Olhos, Rio de Janeiro, Brazil. Methods: Sixteen candidate variables were derived from exported ORA signals to characterize putative indicators of biomechanical behavior. Area under the receiver operating characteristic curve (AUC) and the Z statistic were used to compare diagnostic performance. Main Outcome Measures: Discriminant value of standard and derived ORA variables as measured by AUC. Results: Fifteen of 16 candidate variables performed significantly better than chance (AUC, > 0.5) at discriminating KC. Diagnostic performance was greatest for a custom variable related to the depth of deformation as defined by the minimum applanation signal intensity during corneal deformation (concavity(min); mean AUC +/- standard error, 0.985 +/- 0.002) and a new measure incorporating the pressure-deformation relationship of the entire response cycle (hysteresis loop area, 0.967 +/- 0.002). Z statistics assessing the discriminative value of each of the top 5 variables demonstrated superiority to CH (AUC, 0.862 +/- 0.002). Concavity(min) had the best overall predictive accuracy (cutoff value, 50.37; 94.9% sensitivity, 91.7% specificity, and 93.2% test accuracy), and the top 4 variables demonstrated the most consistent relationships to KC severity. Conclusions: Investigator-derived ORA variables related to the depth of deformation and the pressuredeformation relationship demonstrated very high test accuracy for detecting the presence of KC. Beyond their diagnostic value, the candidate variables described in this report provide mechanistic insight into the nature of the ORA signal and the characteristic changes in corneal dynamics associated with KC. (C) 2014 by the American Academy of Ophthalmology.