Analysis of sequential scanning laser tomography of the optic nerve head must be able to tell disease-induced change from measurement variability if it is to be useful for identifying glaucoma progression. Variability in neuroretinal rim area measurement was found to differ between optic nerves and between regions within each nerve, and was influenced by glaucomatous morphology, varying test conditions and different reference planes. Up to 95% of this variability could be explained by fluctuation in the height between the nerve surface and reference plane, and of the nerve head's centre of gravity along the z-axis. Such fluctuation, whether due to image variability or progressive disease, affects the position of conventional reference planes and limits their usefulness as absolute measures of change. A novel reference plane was designed that is customised to each optic nerve head, lies at a depth compatible with least variability, and stays in position despite glaucomatous damage. Its position in any nerve is calculated from surface height at the nerve margin in multiple topography images, and kept constant throughout each image series. It was found that the reference plane's description of neuroretinal rim was more reproducible and corresponded more closely with actual rim appearance compared with conventional reference planes. An analytical approach was devised to identify change based on this new reference plane. Variability in each 30degree sector of rim area in each nerve was estimated by modelling variability within images from all time-points of any nerve's image series. Confidence limits of variability represented variability in each sector, and only change repeatedly exceeding these limits in two of three tests was attributed to disease. Assessed by 90% and 95% limits of variability, progression was identified with a sensitivity and false positive rate of 90% and 6%, and 83% and 3% respectively in ocular hypertension converter eyes with unambiguous glaucomatous visual field change and unchanging eyes of normal controls. When tested in various presentations of suspected and manifest normal-pressure and high-pressure glaucoma, progression was detected in glaucoma suspect eyes without visual field defects, eyes that progressed to develop field defects, and eyes with established and more severe glaucoma.