A Statistical Approach to the Evaluation of Covariate Effects on the Receiver Operating Characteristic Curves of Diagnostic Tests in Glaucoma

Abstract

To describe an approach for the evaluation of covariate effects on receiver operating characteristic (ROC) curves and to apply this methodology to the investigation of the effects of disease severity and age on the diagnostic performance of frequency doubling technology (FDT) and standard automated perimetry (SAP) visual function tests for glaucoma detection. The study included 370 eyes of 211 participants, with 174 eyes of 110 patients having glaucomatous optic neuropathy and 196 eyes of 101 subjects being normal. All patients underwent visual function testing with FDT 24-2 Humphrey Matrix and SAP SITA (Carl Zeiss Meditec, Inc., Dublin, CA). Disease severity was evaluated by the amount of neuroretinal rim loss assessed by confocal scanning laser ophthalmoscopy. An ROC regression model was fitted to evaluate the influence of disease severity and age on the diagnostic performance of the pattern SD (PSD) index from FDT 24-2 and SAP SITA. After adjustment for age, the areas under the ROC curves (AUCs) for SAP SITA PSD for 10%, 30%, 50%, and 70% loss of neuroretinal rim area were 0.638, 0.756, 0.852, and 0.920, respectively. Corresponding values for FDT 24-2 PSD were 0.766, 0.857, 0.922, and 0.962. For 10% and 30% rim loss, FDT 24-2 PSD had a significantly larger AUC than did SAP SITA PSD. A regression methodology to evaluate covariate effects on ROC curves can be useful for assessment of diagnostic tests in glaucoma. Using the proposed methodology, a significantly better performance of FDT 24-2 compared to SAP SITA for diagnosis of early glaucoma was demonstrated.