Time Lag Between Functional Change and Loss of Retinal Nerve Fiber Layer in Glaucoma.

It is often suggested that structural change is detectable before functional change in glaucoma. However, this may be related to the lower variability and hence narrower normative limits of structural tests. In this study, we ask whether a time lag exists between the true rates of change in structure and function, regardless of clinical detectability of those changes. Structural equation models were used to determine whether the rate of change in function (mean linearized total deviation, AveTDLin) or structure (retinal nerve fiber layer thickness [RNFLT]) was predicted by the concurrent or previous rate for the other modality, after adjusting for its own rate in the previous time interval. Rates were calculated over 1135 pairs of consecutive visits from 318 eyes of 164 participants in the Portland Progression Project, with mean 207 days between visits. The rate of change of AveTDLin was predicted by its own rate in the previous time interval, but not by rates of RNFLT change in either the concurrent or previous time interval (both P > 0.05). Similarly, the rate of RNFLT change was not predicted by concurrent AveTDLin change after adjusting for its own previous rate. However, the rate of AveTDLin change in the previous time interval did significantly improve prediction of the current rate for RNFLT, with P = 0.005, suggesting a time lag of around six months between changes in AveTDLin and RNFLT. Although RNFL thinning may be detectable sooner, true functional change appears to predict and precede thinning of the RNFL in glaucoma.