Global optical coherence tomography measures for detecting the progression of glaucoma have fundamental flaws

OBJECTIVE: To understand the problems involved in using global OCT measures for detecting progression in early glaucoma. SUBJECTS/METHODS: Eyes from 76 patients and 28 healthy controls (HC) had a least two OCT scans at least 1 year apart. To determine the 95% confidence intervals (CI), 151 eyes (49 HC and 102 patients) had at least two scans within 6 months. All eyes had 24-2 mean deviation ≥-6dB. The average (global) thicknesses of the circumpapillary retinal nerve fibre layer (cRNFL), G(ONH), and of the retinal ganglion cell layer plus inner plexiform layer (RGCLP), G(mac), were calculated. Using quantile regression, the 95% CI intervals were determined. Eyes outside the CIs were classified as “progressors.” For a reference standard (RS), four experts evaluated OCT and VF information. RESULTS: Compared to the RS, 31 of the 76 (40.8%) patient eyes were identified as progressors (RS-P), and 45 patient, and all 28 HC, eyes as nonprogressors (RS-NP). The metrics missed (false negative, FN) 15 (48%) (G(ONH)) and 9 (29%) (G(mac)) of the 31 RS-P. Further, G(ONH) and/or G(mac) falsely identified (false positive, FP) 10 (22.2%) of 45 patient RS-NP eyes and 7 (25%) of the 28 HC eyes as progressing. Post-hoc analysis identified three reasons (segmentation, centring, and local damage) for these errors. CONCLUSIONS: Global metrics lead to FPs and FNs because of problems inherent in OCT scanning (segmentation and centring), and to FNs because they can miss local damage. These problems are difficult, if not impossible, to correct, and raise concerns about the advisability of using G(ONH) and G(mac) for detecting progression.