Localized glaucomatous change detection within the proper orthogonal decomposition framework

Abstract

PURPOSE. To detect localized glaucomatous structural changes using proper orthogonal decomposition (POD) framework with false-positive control that minimizes confirmatory followups, and to compare the results to topographic change analysis (TCA). METHODS. We included 167 participants (246 eyes) with >4 Heidelberg Retina Tomograph (HRT)-II exams from the Diagnostic Innovations in Glaucoma Study; 36 eyes progressed by stereo-photographs or visual fields. All other patient eyes (n = 210) were non-progressing. Specificities were evaluated using 21 normal eyes. Significance of change at each HRT superpixel between each follow-up and its nearest baseline (obtained using POD) was estimated using mixed-effects ANOVA. Locations with significant reduction in retinal height (red pixels) were determined using Bonferroni, Lehmann- Romano Κ-family-wise error rate (Κ-FWER), and Benjamini- Hochberg false discovery rate (FDR) type I error control procedures. Observed positive rate (OPR) in each follow-up was calculated as a ratio of number of red pixels within disk to disk size. Progression by POD was defined as one or more follow-ups with OPR greater than the anticipated false-positive rate. TCA was evaluated using the recently proposed liberal, moderate, and conservative progression criteria. RESULTS. Sensitivity in progressors, specificity in normals, and specificity in non-progressors, respectively, were POD-Bonferroni = 100%, 0%, and 0%; POD Κ-FWER 1/4 78%, 86%, and 43%; POD-FDR = 78%, 86%, and 43%; POD Κ-FWER with retinal height change ≥50 lm 1/4 61%, 95%, and 60%; TCA-liberal = 86%, 62%, and 21%; TCA-moderate1/453%, 100%, and 70%; and TCA-conservative = 17%, 100%, and 84%. CONCLUSIONS. With a stronger control of type I errors, Κ-FWER in POD framework minimized confirmatory follow-ups while providing diagnostic accuracy comparable to TCA. Thus, POD with Κ-FWER shows promise to reduce the number of confirmatory follow-ups required for clinical care and studies evaluating new glaucoma treatments. © 2012 The Association for Research in Vision and Ophthalmology, Inc.