The effect of test variability on the structure-function relationship in early glaucoma

To determine whether the weakness of the structure-function relationship could be produced by test variability alone, without implying underlying dissociation between the true rates of structural and functional change. Perimetric mean deviation (MD), and rim area (RA) and cup volume (CV) from confocal scanning laser ophthalmoscopy, over six visits, were taken from 166 eyes of 92 participants with high-risk ocular hypertension or suspected/early glaucoma in the Portland Progression Project. Models were created of each measure's variability. A further model predicted the rate of functional change from the rate of structural change. These were used to generate realistic simulated sequences of both functional and structural data with different standard deviations sigma between the underlying rates of change. 'Observed' structure-function relationships were calculated. An empirical p-value was derived, equaling the proportion of simulated series for which the 'observed' structure-function dissociation was greater than that seen in patient data. The correlation between the rates of structural (RA) and functional (MD) change was 0.171, consistent with sigma < 0.02 dB/yr. Using CV, the correlation was -0.091, consistent with sigma < 0.01 dB/yr. By comparison, the models predicted that the standard deviation of the rate of functional change for a healthy eye due to test variability would be 0.18 dB/yr. Test variability is sufficiently large that realistic patient data can be simulated without requiring a large variability between the underlying rates of structural and functional change. This absence of implied dissociation is a necessary condition for it to be valid to combine structural and functional measures to improve estimates of functional change and/or to reduce perimetric variability.