Does Glaucomatous Structural Damage Indeed Precede Functional Deficit? An Extended Long-Term Cohort Perspective

Abstract

Purpose: Prior studies showing poor correspondence between glaucomatous structural and functional deficits have typically been limited by short duration of follow-up in a slowly progressing disease. The purpose of this study is to evaluate the sequence of progression onsets detectable by optical coherence tomography (OCT) mean retinal nerve fiber layer (RNFL) thickness and by standard automated perimetry (SAP) visual field index in a long-term cohort.

Methods: 211 eyes from 120 healthy, glaucoma suspect, and glaucoma subjects with at least 5 reliable tests for each OCT and SAP. Measurements from four generations of OCT were standardized for comparison by applying calibration equations. OCT and SAP progression was defined as significant negative slope on two consecutive visits. Mean RNFL thickness at time of initial progression was compared between initial OCT progressors and initial SAP progressors.

Results: Median length of follow-up for the cohort was 9.4 years (range 3.9-18.2). No eyes showed coinciding onset of OCT and SAP progression. 40 eyes showed initial progression by OCT with median length of time from baseline to initial progression of 5.9 years (range 2.0-14.8). 18 eyes showed initial progression by SAP with median time to progression of 5.9 years (range 0.9-11.5). Initial SAP progressors had thinner RNFL compared to initial OCT progressors at time of progression (66.9, 79.7µm; p=0.024). Of eyes with initial OCT progression, 5 had subsequent SAP progression. These eyes had thinner RNFL at time of progression compared to eyes with no subsequent SAP progression (62.8, 82.1µm; p=0.045). Of eyes with initial SAP progression, 5 had subsequent OCT progression, with no difference in RNFL thickness between subsequent OCT progressors and non-progressors (66.0, 67.3µm; p>0.05).

Conclusions: An equal number of eyes had OCT progression preceding SAP progression and vice versa. Despite extended follow-up, there was no evidence of a consistent sequence of structural and functional progression. Thinner RNFL in eyes with initial progression by SAP rather than by OCT indicates that OCT progression likely already occurred before our baseline. When initial OCT progression was followed by SAP progression, these eyes probably passed the threshold of structural loss necessary for functional loss to be detectable, as indicated by the thinner RNFL.

Keywords: 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • 758 visual fields • 610 nerve fiber layer