Discriminant value of custom ocular response analyzer waveform derivatives in keratoconus

Abstract

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 pressure-deformation 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.

Figure 1. Representation of Selected Variables

(a) Ocular Response Analyzer Signal Output with selected variables. A1 = first applanation state; A2 = second applanation state; Pmax = maximum achieved pressure; CH = corneal hysteresis. (b) Calculation of Hysteresis Loop Area (HLA). From a single measurement of the Ocular Response Analyzer, Pressure values of the signal output were plotted against Applanation values at each time point. HLA was calculated as the sum of Area 1 and Area 2 within the closed loop. (c) Construction of Hysteresis Loop Area complete (HLAc). To calculate HLAc, Area 1 of the HLA plot in Figure 1b is inverted and yields Area 3. HLAc is the summation of Area 1, Area 2, and Area 3.

Figure 1. Representation of Selected Variables

(a) Ocular Response Analyzer Signal Output with selected variables. A1 = first applanation state; A2 = second applanation state; Pmax = maximum achieved pressure; CH = corneal hysteresis. (b) Calculation of Hysteresis Loop Area (HLA). From a single measurement of the Ocular Response Analyzer, Pressure values of the signal output were plotted against Applanation values at each time point. HLA was calculated as the sum of Area 1 and Area 2 within the closed loop. (c) Construction of Hysteresis Loop Area complete (HLAc). To calculate HLAc, Area 1 of the HLA plot in Figure 1b is inverted and yields Area 3. HLAc is the summation of Area 1, Area 2, and Area 3.

Figure 2. Selected Parameter Trends with Keratoconus (KC) Severity. KC patients were grouped by severity using the Amsler-Krumeich scoring system. All showed a general inverse relationship with disease severity. Sample sizes for each group, however, were not large enough to statistically analyze these trends. n(KC severity 1) = 26 eyes; n(KC severity 2) = 14 eyes; n(KC severity 3) = 5 eyes; n(KC severity 4) = 5 eyes

(a) MinATrough and MeanTrough versus KC Severity score. (b) HLA and HLAc versus KC Severity score. HLA = Hysteresis Loop Area; HLAc = Hysteresis Loop Area complete; (c) CH and CRF versus KC Severity score. CH = Corneal Hysteresis (mmHg); CRF = Corneal Resistance Factor (mmHg).

Figure 2. Selected Parameter Trends with Keratoconus (KC) Severity. KC patients were grouped by severity using the Amsler-Krumeich scoring system. All showed a general inverse relationship with disease severity. Sample sizes for each group, however, were not large enough to statistically analyze these trends. n(KC severity 1) = 26 eyes; n(KC severity 2) = 14 eyes; n(KC severity 3) = 5 eyes; n(KC severity 4) = 5 eyes

(a) MinATrough and MeanTrough versus KC Severity score. (b) HLA and HLAc versus KC Severity score. HLA = Hysteresis Loop Area; HLAc = Hysteresis Loop Area complete; (c) CH and CRF versus KC Severity score. CH = Corneal Hysteresis (mmHg); CRF = Corneal Resistance Factor (mmHg).

Figure 2. Selected Parameter Trends with Keratoconus (KC) Severity. KC patients were grouped by severity using the Amsler-Krumeich scoring system. All showed a general inverse relationship with disease severity. Sample sizes for each group, however, were not large enough to statistically analyze these trends. n(KC severity 1) = 26 eyes; n(KC severity 2) = 14 eyes; n(KC severity 3) = 5 eyes; n(KC severity 4) = 5 eyes

(a) MinATrough and MeanTrough versus KC Severity score. (b) HLA and HLAc versus KC Severity score. HLA = Hysteresis Loop Area; HLAc = Hysteresis Loop Area complete; (c) CH and CRF versus KC Severity score. CH = Corneal Hysteresis (mmHg); CRF = Corneal Resistance Factor (mmHg).