'Structure-function relationship' in glaucoma: past thinking and current concepts

Abstract

An understanding of the relationship between functional and structural measures in primary open-angle glaucoma is necessary for both grading the severity of disease and for understanding the natural history of the condition. This article outlines the current evidence for the nature of this relationship and highlights the current mathematical models linking structure and function. Large clinical trials demonstrate that both structural and functional change are apparent in advanced stages of disease, and at an individual level, detectable structural abnormality may precede functional abnormality in some patients, whereas the converse is true in other patients. Although the exact nature of the 'structure-function' relationship in primary open-angle glaucoma is still the topic of scientific debate and the subject of continuing research, this article aims to provide the clinician with an understanding of the past concepts and contemporary thinking in relation to the structure-function relationship in primary open-angle glaucoma.

Figure 1. The non-linear relationship between dB units and linear (L⁻¹) metrics of differential light sensitivity for standard automated perimetry

A decline of 2 dB from a sensitivity of 32 dB is ten-fold greater, on a linear scale, than a decline of 2 dB from 22 dB.

Figure 2. The ‘Hockey-Stick’ model relating sensitivity and ganglion cell (GC) receptive field number (both in log units)

The datapoints from Garway-Heath et al. (2000) 12 and empirical plot of Swanson et al. (2004) is indicated by the black symbols and solid black line respectively. Anderson & Knighton’s (1988) function , with RGC receptive field number derived from acuity perimetry, is approximated by the grey solid line. The size of the stimulus in relation to the critical area may explain the change in slope at 15 degrees eccentricity. The spatial summation curve predicted by a model of cortical pooling is shown for comparison . See text for details.

Figure 3. Adapted from Kerrigan-Baumrind et al. (2000)

A percentage retinal ganglion cell (RGC) count of 100% (i.e. mean normal) corresponds to a Mean Deviation, MD, value of nearly −6 dB (solid grey lines). The grey shaded box shows points which correspond to a percentage RGC of 100% or greater (Three of these eyes have a MD of less than −5 dB). The lighter grey shaded box shows additional points which lie have a RGC count of greater than 67% and correspond to points which are statistically within confidence limits for normality (at p=5%, one tailed). The black dotted line corresponds to the MD value corresponding to a (one-tailed) p=5% for their data.

Figure 4. Percentage of patients who had the first detectable glaucomatous change on structural or functional testing or both tests in 3 major Clinical Trials;

OHTS = Ocular Hypertension Treatment Study; EMGT = Early Manifest Glaucoma Trial; EGPS = European Glaucoma Prevention Study