PURPOSE: To compare detection of retinal nerve fibre layer changes using GDx guided progression analysis (GPA) fast mode (which assumes fixed variability of a reference population) and extended mode (which measures individual variability), and to determine how they compare with photography and conventional visual field-based methods for identifying glaucoma progression. METHODS: 172 eyes from 117 participants in the Diagnostic Innovations in Glaucoma Study (12 healthy, 108 glaucoma suspects and 52 glaucoma eyes) with ≥ 4 GDx VCC visits and ≥ 3 good quality GDx VCC scans at each visit were included. RESULTS: Agreement between the GDx GPA fast mode and GDx GPA extended mode was limited. The GDx fast mode and extended mode detected 15 and 18 eyes, respectively, as 'likely progression', but only seven of them agreed. The conventional reference standard (stereophotograph-based optic disc and/or visual field progression) identified nine eyes as progressing, of which two eyes were also identified by the GDx fast mode and three eyes by the extended mode. In the GDx fast mode, we found that the progression detection varied depending on which two scans were included in the baseline and follow-up images. CONCLUSION: There was limited agreement between the GDx fast mode and the GDx extended mode for progression detection, and between different scans included in the GDx fast mode progression analysis. Longer follow-up is needed to determine the proportion of eyes classified as 'likely progression' by the GDx analysis that are early change and the proportion that are false positive results.