Use of alternative stimuli
The histological observation that retinal ganglion cells served by larger diameter fibres may be selectively damaged in glaucoma (Quigley, Dunkelberger et al. 1989; Kerrigan-Baumrind, Quigley et al. 2000) has prompted the development of perimetry to target specific ganglion cell classes. However, subsequent analyses have suggested this could be an artefact of shrinkage in the histological sections (Morgan 2002). The mean dendritic field and cell body of parasol ganglion cells is
Rizwan Malik PhD Thesis: Psychophysical & electrophysiological changes in glaucoma
greater than for other retinal ganglion cells (Dacey and Petersen 1992). It has been argued that isolating responses from single ganglion cell classes may aid in earlier identification of abnormality in glaucoma. The parasol ganglion cells and midget ganglion cells form part of the magnocellular and parvocellular pathways respectively. The Koniocellular pathway contains diverse ganglion cell types. Table 1.4 shows the types of stimuli designed to selectively ‘tap’ a subset of ganglion cells.
Table 1.4: Types of perimetry and associated perimetric selective sensitivity
Although some studies have found that FDT may aid in identification of glaucomatous loss before SAP (Sample, Bosworth et al. 2000; Medeiros, Sample et al. 2004), 20% of patients with OHT only have FDT defects (Sample, Bosworth et al. 2000). Sample, Medeiros et al. (2006) found that global indices from FDT were abnormal in about 20% of OHT eyes, questioning its suitability for screening. FDT and SWAP may perform no better than SAP for a population of eyes based on ONH appearance (Tafreshi, Sample et al. 2009).
The Gabor patch stimulus is a sinusoidal patch surrounded by a Gaussian envelope (Gabor 1946). Gabor stimuli resemble the spatial response profile of cortical cells and may provoke a response from a smaller subgroup of ‘spatially-tuned’
Pathway Ganglion cell type Type of perimetry
Magnocellular Parasol FDT, motion detection
Parvocellular Midget HRP
Rizwan Malik PhD Thesis: Psychophysical & electrophysiological changes in glaucoma
mechanisms than a white circular stimulus. Harwerth, Carter-Dawson et al. (1999) used a 1 cycle per degree (cpd) Gabor patch stimulus in sine phase and found the sensitivity for this stimulus to be reduced compared to the Goldmann size III stimulus, with a tendency of Gabor patches to show more generalised perimetric loss. Hot, Dul et al. (2008) used a 0.4 degree cpd Gabor patch to test 20 glaucoma patients and 20 age-similar controls and found that contrast sensitivity measurements were more equivalent to rim area than SAP when measures were converted into percentage of mean normal. Contrast sensitivity has noted to improve following brimonidine therapy (Evans, Hosking et al. 2003), suggesting that this may be a sensitive measure of reversible glaucomatous optic nerve dysfunction.
Use of smaller ‘white’ stimuli than the Goldmann size III
It would seem logical that testing smaller retinal areas would improve the sensitivity to detect damage. Larger stimuli may fall on both normal and damaged retinal ganglion cell receptive fields resulting in near-normal sensitivity. Zalta and Burchfield (1990) tested patients with early glaucoma with both the Goldmann size I and Goldmann size III stimuli. The number of locations with defects of 6 dB or more was greater for the Goldmann size I stimulus, suggesting that this stimulus may be better suited to early detection of functional loss. Similarly, Gramer, Kontic et al. (1981) found that sensitivities were 6-10 dB lower with the Goldmann size I than the Goldmann size III in damaged locations. The main disadvantage of using a small stimulus is that DLS is often not recordable at very damaged locations and high test- retest variability (discussed below) and smaller stimuli are more affected by blur than larger ones (Anderson, McDowell et al. 2001).
Rizwan Malik PhD Thesis: Psychophysical & electrophysiological changes in glaucoma
1.13.2 Reduce variability
Use of larger stimuli than the Goldmann III
The Goldmann size V stimulus, which is 4 times the diameter or 16 times the area of the Goldmann size III, is associated with more uniform variability characteristics than the Goldmann size III (Wall, Woodward et al. 2009). Gilpin, Stewart et al. (1990) found a similar overall variability for the Goldmann size III compared to the Goldmann size V. The ‘total fluctuation’ (calculated from between-test and within- test) was similar for the Goldmann size III compared to the Goldmann sizes IV and V stimulus but lower for the Goldmann I and Goldmann II. Larger stimuli are less affected by optical blur than smaller stimulus sizes (Anderson, McDowell et al. 2001). Anderson, McDowell et al. (2001) found that an optical defocus of +1D affected contrast sensitivity for the Goldmann size III stimulus by approximately twice the amount compared to the same defocus for a size V stimulus in the fovea. The effect of blur on thresholds is eccentricity dependent (Weinreb and Perlman 1986).
Alternative stimuli: sinusoidal stimuli
The variability of the Frequency doubling technology stimulus is less dependent on sensitivity than the Goldmann size III stimulus (Chauhan and Johnson 1994; Spry, Johnson et al. 2001; Wall, Woodward et al. 2009). This effect, at least in part, may be a consequence of a larger stimulus. The peripheral stimuli of the FDTII stimulus subtend 10 by 10 degrees (Alward 2000). It has been argued that the improved sensitivity of the FDT may be a result of selectively tapping the magnocellular
Rizwan Malik PhD Thesis: Psychophysical & electrophysiological changes in glaucoma
pathway, although this hypothesis has been disputed (Swanson, Lee et al. 2010). Similar to the FDT stimulus, Gabor patch variability may exhibit less dependency on depth of perimetric defect than SAP (Pan and Swanson 2006; Hot, Dul et al. 2008).