Absolute Threshold

5.8.1 Introduction

Absolute threshold is a measure of the smallest amount of radiation, which can be perceived by the visual system. In order to measure the absolute visual threshold it is necessary that the eye undergo a sufficient period of dark adaptation i.e. approximately 45 minutes for rods (although many studies will abbreviate this as the bulk of adaptation occurs in the first 15-20 minutes).

The significance o f age in the measurement of absolute threshold o f normals is debatable. Domey et al (1960) studied 241 observers aged between 16 and 89 years and found the absolute thresholds of the elderly to be almost 250 times higher than those of the young observers. When results are corrected for lenticular changes and re-evaluated, it can be seen that rod threshold, measured after 40 minutes dark adaptation, remains almost constant through the first 6 decades o f life, and then begins to rise. The cone threshold does not show the same age-related decline. The age-matching of subjects in comparisons between thresholds o f AMD and normal groups is, therefore, of importance in the consideration of rod sensitivity.

5.8.2 Absolute Threshold and AMD

Brown & Lovie-Kitchin (1983) measured rod sensitivity at an eccentricity o f 10°, following 20 minutes dark adaptation. The average threshold of the 8 AMD subjects tested was found to be significantly elevated compared to age-matched controls, by an average of 0.33 log units. However, the subjects with AMD used in this study were very wide-ranging in the extent of their visual deficit, with visual acuity ranging from 6/9 to 6/120. The group-averaged results do not indicate to what extent absolute threshold is affected in the early stages of AMD. Recent work by Jackson et al (1998) suggested that, whilst there is an age-related loss in absolute sensitivity o f older individuals, rod sensitivity is not significantly different in subjects of a similar age with and without early ARM.

There are more studies o f the loss of absolute sensitivity in the cone pathway in AMD. Steinmetz et al (1993) investigated the dark-adapted foveal sensitivity of 12 individuals with ARM. Foveal thresholds were found to be more variable in the ARM group compared to age-

Chapter 5 Visual Psychophysics

matched controls, and were depressed by at least 10 dB in 6 of the 12 subjects. However, there was no relationship between the number of drusen and the magnitude of scotopic sensitivity loss. Similar losses in cone sensitivity in individuals with AMD have been reported in other studies (Brown & Lovie-Kitchin, 1983; Brown et al, 1986). The parafovea appears to be particularly vulnerable to functional deficit (Brown et al, 1986)

Eisner et al (1987; 1991; 1992) evaluated the prognostic value o f cone thresholds. An initial cross-sectional study (Eisner et al, 1987) investigated cone sensitivity in 21 individuals with unilateral neovascular AMD in the non-test eye, and compared this with results taken from 130 subjects with bilateral drusen. Eisner found absolute cone thresholds to be lower for the subjects with unilateral exudative AMD in the contralateral eye, thus indicating that this parameter may be a potential risk indicator for future neovascular changes in an eye with drusen. Furthermore, a second cross-sectional study (Eisner et al, 1991) found raised cone thresholds to be related to a fundus appearance indicative of a high risk of CNV. A prospective study to further investigate this finding involved the baseline assessment of cone threshold in forty-seven subjects with exudative AMD in the non-test eye (Eisner et al, 1992). Eleven of the 47 subjects developed neovascular changes over the 18 month follow-up period. Absolute cone sensitivity in this case, however, did not help to predict the outcome after the effects of age had been removed.

Another longitudinal study (Sunness et al, 1989) followed 18 individuals with ARM over a period of 45 months. Sunness found that, at baseline, those individuals who were to develop advanced retinal changes (n=5) had a significantly reduced dark-adapted foveal sensitivity compared to those who remained unconverted throughout the study. With an optimal cut-off point in baseline foveal threshold it was possible to predict with 100% sensitivity, and 92% specificity the outcome o f the subjects over the follow-up period. The significance o f these results was limited, however, by the small subject group involved. The study also differed from Eisner’s (1992) in that it did not discriminate between a dry and an exudative advanced AMD outcome, possibly explaining the disparity in results. However, a further longitudinal study by Sunness et al (1997) followed a larger group of 74 subjects with dry AMD, and visual acuity of 6/15 or better. The foveal dark-adapted threshold once again showed some promise at predicting outcome, with a reduced foveal dark adapted sensitivity at baseline accounting for an increased risk o f a doubling o f the minimum angle of resolution over the 2 year follow-up.

Chapter 5 Visual Psychophysics

5.8.3 S-Cone Sensitivity and AMD

In addition to general measurements of rod and cone absolute thresholds, further studies have investigated the sensitivity of the S-cone pathway in AMD. In humans, S-cones only comprise 5-10% of the cone mosaic, with the greatest density falling in the parafoveal region {See

Calkins et al, 2001, fo r review). It is this region which has been suggested to be vulnerable to

early AMD {see Curcio, 1996). S-cone photoreceptors are also believed to be more susceptible to metabolic damage than L- and M-cones {Hood & Greenstein, 1988). Colour- vision studies have suggested that the earliest defects recorded in people with AMD are tritanopic in nature {e.g. Cheng & Vingrys, 1993; Collins & Brown, 1989; Haegerstrom-

Portnoy et al, 1988), again suggesting an early involvement of the S-cone pathway in the

disease process.

Eisner et al {1991) investigated S-cone function in a cross-sectional study of 41 individuals with drusen in the study eye and unilateral exudative AMD in the fellow eye. The subjects were classified as being at high- and low-risk o f developing exudative AMD in their test eye, according to retinal appearance. High-risk eyes appeared to have a lower S-cone mediated sensitivity than low-risk eyes. To ameliorate the possible confounding effect of age on the S- cone sensitivities measured in the two groups, a further comparison was made within a limited age range o f 66-74 years, the difference remained significant (P<0.05). A similar study by Sunness et al {1989), investigating S-cone sensitivity in 31 individuals with drusen, also found that the 13 eyes with high-risk drusen had reduced sensitivity compared to eyes with low risk drusen, although there was considerable overlap between the groups.

DeMonasterio et al {1985) reported that the spatial density o f S-cones decreased in the central fovea for old female, but not for old male macaques, which would suggest that gender should be taken into account when analysing the effects of age and AMD on the S-cone system. In Eisner’s study {1991), the high-risk eyes o f men had a significantly lower S-cone mediated sensitivity than the low-risk eyes, whereas this comparison was not significant for women, although this was possibly linked to the smaller number of women in the study.

Eisner’s longitudinal study {1992) into the prognostic value of the measurement of retinal sensitivity in AMD suggested that S-cone sensitivity is better able predict the onset of CNV than absolute sensitivity. When S-cone sensitivity was plotted against age for those eyes which did not develop CNV over the 18 months of the study, 6 of 11 exudative outcome eyes fell below the curve.

Chapter 5 Visual Psychophysics

These results support the theory that S-cones may be sensitive to damage in AMD. It appears that measurements of S-cone sensitivity may be of possible use in assessing the likelihood of an individual developing advanced AMD, but further investigations on a larger group of subjects would be required to determine the precise cut-off point in threshold of high-risk eyes. Eisner (1992) also highlighted the fact that S-cone sensitivity is highly dependent on age and media absorption, factors making it a complicated predictor of retinal changes.