Introduction
An improved understanding of the relation between mild ganglion cell loss and visual function may aid the development of new tests of visual function to detect loss in the early stages of glaucoma. Toward this end, the relationship between ganglion cell loss and decline in visual function has been studied extensively in patients with glaucoma, and it is well established that significant declines in visual sensitivity are often present when glaucomatous ganglion cell loss is mild.
Although the normal variability in ganglion cell measures is high and limits the ability to detect mild ganglion cell loss in individual subjects, cross-sectional studies have produced strong evidence that mild ganglion cell losses are a normal part of aging. Both histologic and imaging studies have found an average of 10% to 30% loss of ganglion cells between the third and seventh decades of life. Some of the early attempts to quantify the relation between ganglion cell loss and standard perimetric measures interpreted their data with the idea of a “functional reserve” of ganglion cells with enough redundancy that a significant loss of perimetric sensitivity required 20% cell loss in the central visual field and 50% cell loss in the macula. However, later studies in humans and monkeys have reported that substantial perimetric defects (on the order of −6 dB) occurred when there was little or no ganglion cell loss. Recent imaging and electrophysiological studies in individuals with glaucoma have concluded that visual loss measured with standard achromatic perimetry proceeds at the same rate as ganglion cell loss when both histologic and perimetric measures are plotted in linear units. Therefore, measures of visual function can be used to quantify the loss of ganglion cells even when those losses are mild.
The cortical pooling model is a two-stage neural model that includes both the effect of the density of the ganglion cell mosaic and the linear summation of information from that mosaic by spatial filters. In the first stage of the model, ganglion cell responses are computed for perimetric stimuli. The probability of detecting a stimulus was modeled in the second stage in terms of the responses of spatial filters that linearly sum the weighted responses from the ganglion cells in the first stage. In addition to accounting for losses in perimetric sensitivity in individuals with glaucoma, the cortical pooling model overcomes both of the aforementioned difficulties: the model is quantitative, and it can be used to predict the effects of varying stimulus parameters on the detection of ganglion cell loss. If the model is successful in predicting the influence of stimulus parameters on the detection of visual losses resulting from ganglion cell loss, the model holds great potential for providing guidelines for the development of clinical tools for the detection of early ganglion cell loss. Therefore, studies evaluating whether the predictions of the model can account for the effects of stimulus parameters on change in visual sensitivity consequent to ganglion cell loss are imperative.
The two-stage model yields a number of predictions about the influence of stimulus size and chromaticity on the magnitude and variability of the visual loss that can be expected to accompany age-related losses in ganglion cells. In this model, sensitivity declines linearly as the number of ganglion cells decline only when the mechanisms mediating detection are tuned to spatial frequencies that are low relative to ganglion cell density. That is, the responses of the spatial filters are more affected by mild heterogenous losses of ganglion cells when the spatial filters pool the responses from a large number of ganglion cells. In contrast, when spatial filters pool the responses from a relatively small number of ganglion cells, visual sensitivity remains near normal until there has been a large amount of ganglion cell death or dysfunction. If the peak spatial frequency of the filters is relatively low, the model predicts that density of the mosaic has very little influence on the sensitivity to ganglion cell loss. If the peak spatial frequency of the filters is relatively high, however, the model predicts, contrary to reduced redundancy theories, that those tests that isolate the response of dense ganglion cell mosaics will better detect ganglion cell loss. Based on the greater spatial summation properties of the chromatic pathways, it is expected that the age-related visual losses will decrease in magnitude when the size of an achromatic stimulus is increased but not when the size of a chromatic stimulus is increased. Therefore, the age-related decreases in visual sensitivity obtained with the large chromatic stimuli will be similar to one another and to those obtained with the small achromatic stimuli. It is also expected that the dependence of variability on sensitivity to small achromatic stimuli will be lessened as the size of the chromatic and achromatic stimuli is increased.
Finally, similar to the reduced redundancy model, the cortical pooling model predicts that selective losses in visual sensitivity mediated by different pathways can result from equal losses in the ganglion cells in the different pathways (i.e., selective visual impairments do not necessarily reflect selective or greater loss of one type of ganglion cell over another). Thus, although the age-related loss of ganglion cells is equal across ganglion cell classes, we expect that selective visual losses will be observed because the peak spatial frequency of the filters mediating detection of the different stimuli is varied.
Results
When the stimuli were large, threshold measurements obtained from all participants were reliable and well within the range of modulations along the chromatic axes that could be produced by the phosphors of the CRT. For the large stimuli, neither long- nor short-term variability increased as a function of age. Increasing the size of the stimulus did not decrease the magnitude of the age-related losses when the stimulus was chromatic, and visual losses observed with large chromatic stimuli were not different from those obtained with small achromatic stimuli. Moreover, chromatic contrast sensitivity assessments identified significant visual losses in four individuals who were not identified by achromatic contrast sensitivity assessments and only missed identifying one individual with significant losses in achromatic contrast sensitivity.
Conclusions
The declines in achromatic and chromatic sensitivity as a function of age (0.4 – 0.7 dB per decade) were similar to those obtained in previous studies of achromatic and chromatic perimetry and are consistent with the loss of retinal ganglion cells reported in histologic studies. The results of this study are consistent with the predictions the cortical pooling model makes for both variability and contrast sensitivity. These findings emphasize that selective visual impairments do not necessarily reflect preferential damage to a single ganglion cell class and that it is important to include the influence of higher cortical processing when quantifying the relation between ganglion cells and visual function.
