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patient or photographs of the ONH or RNFL. However, there is little support for this view in the literature, with studies showing that only the most expert clinicians (or a consensus of experts) perform better than quantitative imaging devices (Wollstein et al., 2000; Deleon-Ortega et al., 2006; Reus et al., 2007).

Selective tests of visual function

An early histological study of glaucoma suggested that there may be preferential loss of larger retinal ganglion cells (Quigley et al., 1987) and this finding spawned the development of ‘‘selective’’ psychophysical tests that stimulate subsets of ganglion cells with larger axons — those subserving the blue/yellow (koniocellular) and the motion and flicker (magnocellular) pathways. However, more recent work suggests that there is no preferential loss of larger fibers, but shrinkage of all fibers as part of the glaucomatous process (Morgan, 2002; Yucel et al., 2003).

Psychophysical tests have been used to probe the parvocellular (acuity), koniocellular, and magnocellular pathways in glaucoma, in an attempt to identify preferential damage in one or other pathway. The results of these studies provide conflicting evidence (Anderson and O’Brien, 1997; Harwerth et al., 1999; Ansari et al., 2002). The literature concerning the sensitivity of selective vision function tests to identify early glaucoma is extensive, yet appropriately designed studies are rare. Most studies suffer from design bias similar to that outlined above for studies assessing the value of structural measurements in early glaucoma — subjects are selected for having normal SAP and then are tested with ‘‘selective’’ visual function tests, such as FDT perimetry and SWAP. Unsurprisingly, glaucoma suspect patients with normal SAP are found with abnormal FDT and SWAP and the erroneous conclusion is drawn that FDT and SWAP are more sensitive than SAP. However, by definition (as a result of the study design), these patients have to have normal SAP, and there is no opportunity to find patients that have abnormal SAP and normal SWAP or FDT. The appropriate study design to compare SAP, SWAP, and FDT, or any

other test of visual function, is to use a reference standard for glaucoma that is independent of the tests being evaluated, such as a structural measurement of the ONH or RNFL (Stroux et al., 2003; Sample et al., 2006). Similarly, when quantitative imaging devices are being evaluated, the appropriate reference is the visual field (and not the appearance of the ONH and RNFL) (GarwayHeath and Hitchings, 1998b; Medeiros, 2007).

Early glaucoma diagnosis from quantitative test results

The sensitivity of various imaging devices, available as clinical tools, to identify early glaucoma has been compared against the appropriate reference standard of early SAP loss (Medeiros et al., 2004). The study by Medeiros and colleagues did not use a clinical evaluation of the ONH or RNFL as a selection criterion for glaucomatous subjects in the study, although they did require normal subjects to have a healthy appearance of the ONH and RNFL. This may result in an over-estimation of the diagnostic performance of the devices. The sensitivity of the devices (GDxVCC Nerve Fiber Analyzer, Heidelberg retina tomograph II, and Stratus Optical Coherence Tomograph), at a fixed specificity of 95%, for early glaucoma (average mean deviation 4.9 dB) is given in Table 1.

In a study with a similar design, Sample and colleagues evaluated the sensitivity of various vision function tests (SAP, SWAP, FDT, and high-pass resolution perimetry) to identify early glaucoma with the appropriate reference standard of ONH structure (Sample et al., 2006). Normal eyes had a normal-appearing ONH and glaucoma eyes had either a glaucomatous-appearing ONH or progressive changes in ONH appearance. There was little difference in the performance of the various vision function diagnostic tests in the subjects with a glaucomatous-appearing ONH. In the eyes with progressive changes in ONH appearance, FDT performed better than the other tests. Table 2 gives the sensitivity of the tests in all glaucoma subjects.

Taking the results of these two studies together, it can be seen that neither structure nor function is consistently abnormal before the other in early